Genetic basis of bats superpowers revealed – KLBK | KAMC | EverythingLubbock.com

LUBBOCK, Texas (NEWS RELEASE) The following is a news release from Texas Tech University:

For the first time, the raw genetic material that codes for bats unique adaptations and superpowers such as the ability to fly, use sound to move effortlessly in complete darkness, survive and tolerate deadly diseases and resist aging and cancer has been fully revealed andpublished in Nature.

Bat1K, a global consortium of scientists dedicated to sequencing the genomes of every one of the 1,421 living bat species, has generated and analyzed six highly accurate bat genomes that are 10 times more complete than any bat genome published to date, in order to begin to uncover bats unique traits.

Given these exquisite bat genomes, we can now better understand how bats tolerate viruses, slow down aging and have evolved flight and echolocation, said Emma Teeling of University College Dublin, co-founding director of Bat1K and senior author on the paper. These genomes are the tools needed to identify the genetic solutions evolved in bats that ultimately could be harnessed to alleviate human aging and disease.

As part of the consortium, two researchers inTexas Tech UniversitysDepartment of Biological Sciences, associate professorDavid A. Rayand doctoral candidateKevin Sullivan, played a pivotal role in the genome analysis.

Our lab was tasked with analyzing the portions of each genome that are made up of transposable elements, parts of the genome that can move around and potentially disrupt or alter function, Ray said. We found that, unlike most other groups of mammals, bats have an exceptionally diverse transposable element repertoire. This suggests their genomes may have the ability to change and adapt to novel environments above and beyond what a typical mammal can do. This may explain what appears to be their increased ability to tolerate viruses and live longer, healthier lives than would be expected given their size.

Ray explained that a perfectly assembled genome would have the same number of pieces as there are chromosomes for that species. For example, humans have 23 pairs of chromosomes so a very good assembly would consist of 23 pieces of assembled DNA. In contrast, bad genome assemblies have thousands of pieces, meaning the assembly is very fragmented. Because these bat genomes have very few pieces, the researchers refer to them as exquisite genomes.

To generate these exquisite bat genomes, the Bat1K team used the newest technologies of the DRESDEN-concept Genome Center, a shared technology resource in Dresden, Germany, to sequence the bats DNA, and generated new methods to assemble these pieces into the correct order and to identify the genes present.

Using the latest DNA sequencing technologies and new computing methods for such data, wehave 96-99% of each bat genome in chromosome-level reconstructions an unprecedentedquality akin to, for example, the current human genome reference, which is the result of over adecade of intensive finishing efforts, said senior author Eugene Myers, director of Max Planck Institute of Molecular Cell Biology and Genetics, and the Center for Systems Biology in Dresden. As such, these bat genomes provide a superb foundation for experimentation and evolutionary studies of bats fascinating abilities and physiological properties.

The team compared these bat genomes against 42 other mammals to address the unresolved question of where bats are located within the mammalian tree of life. Using novel phylogenetic methods and comprehensive molecular data sets, the team found the strongest support for bats being most closely related to a group called Ferreungulata that consists of carnivores (whichincludes dogs, cats and seals, among other species), pangolins, whales and ungulates (hooved mammals).

To uncover genomic changes that contribute to the unique adaptations found in bats, the team systematically searched for gene differences between bats and other mammals, identifying regions of the genome that have evolved differently in bats and the loss and gain of genes that may drive bats unique traits.

Our genome scans revealed changes in hearing genes that may contribute to echolocation,which bats use to hunt and navigate in complete darkness, said senior author Michael Hiller, research group leader in the Max Planck Institute of Molecular Cell Biology and Genetics, the Max Planck Institute for the Physics of Complex Systems and the Center for Systems Biology.

Furthermore, we found expansions of anti-viral genes, unique selection on immune genes, and loss of genes involved in inflammation in bats. These changes may contribute to bats exceptional immunity and points to their tolerance of coronaviruses.

The team also found evidence that bats ability to tolerate viruses is reflected in their genomes. The exquisite genomes revealed fossilized viruses, evidence of surviving past viral infections,and showed that bat genomes contained a higher diversity than other species providing agenomic record of historical tolerance to viral infection.

Given the quality of the bat genomes, the team uniquely identified and experimentally validatedseveral non-coding regulatory regions that may govern bats key evolutionary innovations.

Having such complete genomes allowed us to identify regulatory regions that control geneexpression that are unique to bats, said senior author Sonja Vernes of the Max Planck Institute for Psycholinguistics and co-founding director of Bat 1K. Importantly, we were able to validate unique bat microRNAs in the lab to show their consequences for gene regulation. In the future we can use these genomes to understand how regulatory regions and epigenomics contributed to the extraordinary adaptations we see in bats.

This is just a beginning. The remaining approximately 1,400 living bat species exhibit an incredible diversity in ecology, longevity, sensory perception and immunology, and numerous questions remain regarding the genomic basis of these spectacular features. Bat1K will answer these questions as more and more exquisite bat genomes are sequenced, further uncovering the genetic basis of bats rare and wonderful superpowers.

This study was funded in part by the Max Planck Society, the European Research Council, theIrish Research Council and the Human Frontier Science Program.

In addition to Texas Tech, the institutions contributing to the research are: University College Dublin; Max Planck Institute of Molecular Cell Biology and Genetics; Max Planck Institute for the Physics of Complex Systems; Center for Systems Biology; Max Planck Institute for Psycholinguistics; Australian National University; University of Oxford; Stony Brook University; John Jay College of Criminal Justice; University of Bristol; Max Planck Institute of Animal Behavior; University of Konstanz; Smithsonian Tropical Research Institute; University of Montpellier; University of Greifswald; The Rockefeller University; Howard Hughes Medical Institute; Donders Institute for Brain, Cognition and Behaviour; and Technical University Dresden.

(News release from Texas Tech University)

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Genetic basis of bats superpowers revealed - KLBK | KAMC | EverythingLubbock.com

Study of Gene’s Hormone Effects Leads to Surprise Insight into Pituitary Tumors – University of Michigan Health System News

Rathkes cleft cysts are benign, fluid filled growths that develop in the pituitary gland, a small oval-shaped gland near the underside of the brain. Usually, these cysts dont cause symptoms. However, if they become large enough to compress the organ and surrounding tissues, then they can cause problems with vision and the secretion of hormones from the pituitary gland. Treatment for these cysts may involve draining the fluid and surgical removal.

Little is known about why these cysts form. The authors of a new paper in the Journal of Clinical Investigation, led by Sally Camper, Ph.D., the Margery Shaw Distinguished University Professor of Human Genetics, have developed a model of Rathkes cleft cysts by breeding mice that lack the gene for a protein called Islet 1 in the developing pituitary gland.

They discovered that the cysts arise from pituitary stem cells that have adopted the wrong cell fate without the guidance of Islet 1, which normally drives pituitary hormone production. The animal model allowed them to examine the development of the cysts over time and identify markers that could be used by pathologists to diagnose Rathkes cleft cysts. Typically, the cysts are identified using brain scans.

The development of the cysts was a surprise, says Camper. We were interested in whether the Islet 1 gene has a role in pituitary hormone production the same way it does in the pancreas, where it drives expression of insulin and other pancreatic endocrine hormones. The accidental finding shows how researching the basics of how organs develop can lead to discoveries that are clinically relevant, she adds.

First authors on the paper were Michelle Brinkmeier and Hironori Bando, Ph.D. of the U-M Medical Schools Department of Human Genetics.

Paper cited: "Rathkes cleft-like cysts arise fromIsl1deletion in murine pituitary progenitors," Journal of Clinical Investigation.DOI:10.1172/JCI136745.

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Study of Gene's Hormone Effects Leads to Surprise Insight into Pituitary Tumors - University of Michigan Health System News

Dutch University hospital Radboudumc finds genetic mutation as a reason for lack of defense against corona – Innovation Origins

Two brothers from the Dutch village of Beek en Donk were 29 and 31 years old when Corona hit them hard. At the first peek of the pandemic in the Netherlands, they were proof that COVID-19 did not only affect the elderly. The brothers ended up in intensive care, where they were kept in an artificial coma. The eldest eventually managed to survive, the youngest did not.

The distressing events were the beginning of a search by doctors and geneticists of the Nijmegen Radboudumc for genetic factors in a humans defence. Their research makes it clear that TLR7 Toll-like receptor 7 plays an essential role in the disease process. A finding with potentially major consequences, with which Radboudumc came out yesterday in a publication in JAMA. There is good hope that this might even result in a treatment for new Corona patients.

In the wave of COVID-19 patients that engulfed Dutch hospitals in the first half of 2020, an attentive physician from the clinical genetics department of the Maastricht MUMC+found something remarkable, which would be the start of important scientific research at the Radboudumc. Two young brothers within the same family who became seriously ill because of the SARS-CoV-2 virus and had to go to the ICU for ventilation. One of them died from the consequences of the infection, the other recovered. Remarkable, because it was mainly elderly people who were affected by the virus and in this case two brothers under the age of 35 from the same family.

In such a case you immediately wonder whether there are also genetic factors involved, says geneticist Alexander Hoischen. Getting sick from an infection is always a combination between in this case the virus and mans defence. The fact that two brothers from the same family become so seriously ill may, of course, be a coincidence. But it is also possible that a congenital abnormality in their defence played an important role. We started investigating the latter with our multidisciplinary team in the Radboudumc.

From both brothers, all genes with a function (the exome) were mapped. Subsequently, a possible cause is searched for. Cas van der Made, a Ph.D. student at the Department of Internal Medicine: In doing so, we mainly looked at genes that play a role in the immune system. We know that many of these important genes are located on the X chromosome. Women have two X chromosomes; men have a Y chromosome in addition to the X-. So men only have one copy of the genes on the X chromosome. If something is wrong with that, there is no second gene that can take over that role, as there is in women.

So it looks like the virus can just go ahead because the immune system doesnt get a message that the virus has gotten in.

During that research, the gene encoding for the Toll-like receptor 7, or TLR7 for short, soon came into the picture. There are several TLR genes, but they all have in common that they play an important role in recognizing pathogens and activating the innate immune system. Hoischen: A few letters were missing from the genetic code of that TLR7. As a result, the code could not be read properly and hardly any TLR7 was made. Until now, the function of TLR7 has never been associated with a congenital immune disorder. But suddenly, we now see that TLR7 is apparently essential to identify this coronavirus. It seems as if the virus can follow its course because the immune system does not receive any message that the virus has entered. Because TLR7, which is supposed to identify the intruder and then activate the immune system, is hardly present at all. That could be the reason for the serious course of the disease.

Quite unexpectedly, the doctors and researchers in the Radboudumc again had to deal with two seriously ill brothers with COVID-19. The two were even younger: 21 and 23 years old. Both also had to go to the ICU for ventilation. Then the question of the role of the genes is even more obvious, says Hoischen. We carried out the same research with these two brothers, again using the unique rapid-exome diagnostic route. This time we saw no deletion, no loss of letters, but only a single writing error in the TRL7 gene. The effect is the same because these brothers also do not make TLR7 sufficiently effective either. Suddenly we had four young people with a defect in the same gene who had all become seriously ill because of the SARS-CoV-2 virus.

Van der Made and his colleagues have figured out how the mechanism works. Once activated, TLR7 ensures the production of so-called interferons, signal proteins that are essential in the defense against viral infections, says van der Made. This immune response is perhaps all the more important in the fight against the SARS-CoV-2 virus because we know from the literature that this virus has tricks to reduce the production of interferons by immune cells. When mimicking an infection with the coronavirus, we see that the immune cells of the patients without a properly functioning TLR7 hardly react and that hardly any extra interferons are produced. These tests show that the virus seems to have free rein in people without a properly functioning TLR7 because it is not recognized.

Due to the serious illness with two brothers in two families, from which one of the young men died, we have come on the trail of this condition, says Hoischen. It appears to be a very specific abnormality, an immune deficiency, mainly related to this coronavirus. None of the four men had previously suffered from the defense or immunity. Its the first time that weve been able to connect a clinical picture so strongly to this TLR7.

This discovery not only gives us more insight into the fundamental functioning of the immune system but may also have important consequences for the treatment of seriously ill COVID-19 patients, says immunologist Frank van de Veerdonk. The substance interferon can be given as therapy. It is currently being investigated whether giving interferon to COVID-19 can indeed help.

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Dutch University hospital Radboudumc finds genetic mutation as a reason for lack of defense against corona - Innovation Origins

Tailoring Depression Treatment With Genetics – Technology Networks

New research led by Kings College London has found that measuring levels of inflammation and stress-response in the blood may provide useful information to show which patients with depression will or will not respond to treatment with antidepressants.In addition, these findings could potentially help towards developing personalized treatments for depression that involve the use of anti-inflammatories.

The study was led by Kings College London and involved researchers from IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli (Brescia, Italy), University of Milan (Italy), University of Cambridge, University of Oxford, University of Glasgow, Cardiff University, and Janssen Pharmaceutica.

Published in Translational Psychiatry, the study examined the blood from 130 patients with major depressive disorder (MDD) and 40 healthy controls to understand how gene expression - the process which signals the production of new molecules - could be used to distinguish those patients with treatment-resistant depression (TRD) from those who are responsive to medication. The participants were recruited as part of the Biomarkers in Depression (BIODEP) Study.

About 1 in 5 people suffer from depression in the UK and up to one third of these are considered resistant to treatment, which means that medication has no measurable effect and they have fewer options for managing their depression.

While there is overwhelming evidence of increased inflammation in depression it is still unclear how exactly this occurs and what it looks like at the level of chemistry within the body, said Dr Annamaria Cattaneo from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) Kings College London, lead author on the paper.

She added, In this study we show for the first time that it is possible to distinguish patients with depression who do not respond to medication from those who are responding to the antidepressant medication, based on the levels of well-known measures of inflammation and the presence of molecular mechanisms that put this inflammation into action. This could potentially provide a means to assess which treatment options may be more beneficial from the outset.

The researchers observed notably stronger molecular signs of inflammation and stress in both the patients who were not responding to antidepressant treatment and patients who were medication-free, compared with patients with depression who were responsive to medication and healthy controls. These findings support the growing evidence that patients that do not respond to antidepressants or have untreated depression have heightened inflammation compared with controls.

Previous research has shown that high levels of C-reactive protein (CRP) in the blood indicate some degree of inflammation in the body and, in the present study, researchers found higher levels of blood CRP in both patients that were resistant to treatment and medication-free patients compared with patients with depression who were responsive to medication as well as healthy controls. Likewise, researchers reported that the expression of several inflammation-related genes (including IL-1-beta, IL-6, TNF-alpha, and P2RX7) was also increased in both treatment resistant and medication-free patients.

Some of the 16 genes measured in this paper had never before been measured in human blood.

Researchers also examined indicators of stress and found that both the treatment resistant and drug-free patients have reduced numbers of glucocorticoid receptors which are involved in the bodys stress response. With reduced numbers of receptors, the bodys ability to buffer stress through hormones such as cortisol is diminished, which increases the risk of more severe forms of depression.

Our study has provided important insight into the mechanisms that can explain the link between inflammation and depression which will especially impact the future of personalised psychiatry, said senior author of the study, Professor Carmine Pariante from the IoPPN, Kings College London.

He continued, While much of drug-based intervention currently relies on a trial and error approach, studies such as this implore investigation into identifying sub-groups of patients with depression such as treatment resistant patients with inflammation so that patients may be guided directly to treatment strategies which work best for them.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Tailoring Depression Treatment With Genetics - Technology Networks

Genetic puzzle: How mice can be modified to help in the race to develop coronavirus therapies – Genetic Literacy Project

For more than three decadesMichael Koob has been working out complicated puzzles using the tools of molecular biology and genetics. Today his deliberative labors are paying offwith untold implications for the study of human disease and the development of drug therapies and vaccines. Koob has figured out how to replace entire genes of laboratory mice with their human counterparts, transporting huge segments of human DNA to their proper corresponding location in mouse chromosomes. Now he is applying his genetic puzzle-solving ingenuity to the scourge of the COVID-19 pandemic.

An LMP associate professor, Koob launched his molecular investigations while a graduate student at the University of Wisconsin in Madison, where he earned a PhD in molecular and cellular biology in 1990. His graduate adviser was the legendary molecular geneticist Waclaw Szybalski. Koob and Szybalski pioneered a technique they called Achilles heel cleavage that cuts DNA in a single targeted location, which enabled them to create large DNA segments. Koob joined the LMP faculty in 1995. He brought with him those early insights about how to use molecular tools to manipulate DNA in human and animal cells and thereby answer questions about health and disease.

Now Koob has set his sights onCOVID-19, the disease caused by coronavirusSARS-CoV-2 infection. SARS-CoV-2 respiratory viruses enter human lung tissue via a cell-surface receptor molecule called angiotensin-converting enzyme 2 orACE2. Once in the lung the virus multiplies and travels throughout the organ, in some patients causing Acute Respiratory Distress Syndrome (ARDS), which can be fatal.

But theres a problem in using mice to understand SARS-CoV-2 infection and COVID-19 disease progression. In the mouse, the ACE2 receptor doesnt bind the virus, so mice dont get infected and show the respiratory symptoms we see in people, Koob said. But what if mice expressed the human gene for the ACE2 receptor instead of their own? That would potentially enable investigators to track COVID-19 pathology beginning with infection and viral replication in airway epithelial cells all the way to lower lung zones where the virus often settles, consolidates, and can cause viral pneumonia. That mouse model is under construction in Koobs laboratory.

Infection at the entry point would make the mouse model work for COVID-19, and full human ACE2 receptor gene substitution for the mouse version should make infection possible, Koob said. The internal viral replication will be maintained between the mouse and humans. So this should model the infection route, disease progression in the lungs, everything like that. Its really just basic cell biology. If you want to mimic what happens in a person the most important thing really is to get the cell types correct. If the right cells are ACE2 receptor-positive, then you can mimic what happens in people.

Other research groups have transferred only a small part of the ACE2 receptor DNA gene sequence into mice, creating transgenic animals but ones that do not mimic the potentially lethal lung pathology of a SARS-CoV-2 infection and COVID-19, such as ARDS. Koobs team will replace the entire mouse ACE2 receptor gene with the entire human ACE2 receptor gene plus associate regulatory sequencestransferring in all some 70,000 DNA sequences to the precise location on the mouse chromosome where its own ACE2 receptor gene once resided. The mouse gene will be gone, and the human gene will be there, Koob said. It now becomes a human ACE2 receptor gene in a true sense. The sequence of tissues that become positive for ACE2 receptor expression should be recapitulated.

When a human gene is put in the same spot where the mouse gene once resided, genomic regulatory factors come into play that are appropriate for that gene, Koob said. Theres a global regulatory context to take into account in animals that have a common ancestor, which all mammals do. Mice and humans arefairly close on the evolutionary tree. So theres global regulation if we put it in the right spot. The right spot transfer of the human gene construct is into a mouse embryonic stem cell, which Koob then puts into a blastocyst or early mouse embryo. Selective breeding yields mice with the human gene in all cells and tissues.

A search of the databaseClinicalTrials.govyields more than 400 studies when the terms COVID-19 and lung therapy are combined. Small molecule drugs, therapeutic antibodies and antivirals, immunotherapies, stem cells and natural killer cells, steroids, and laser and radiotherapies are among the lung injury therapies currently being investigated. A validated, reliable, and clinically informative mouse model for testing COVID-19 lung injury therapies would be invaluable, as it would be for future coronavirus vaccine trials.

Koob anticipates his human ACE2 receptor gene mouse strain will be ready by this fall. He will send it by courier toJackson Laboratory(JAX) in Bar Harbor, Maine to join more than 11,000 strains of mice that JAX distributes to researchers around the world. JAX will breed the mice over several months while Koob and LMP professorsSteve JamesonandKris Hogquistand Department of Medicine assistant professorTyler Bold, all at the Center for Immunology, conduct characterization and SARS-CoV-2 infection studies of the mice in aLevel 3 biosafetyfacility. JAX is currently distributingKoobs full gene replacement mouse strainthat carries the human microtubule-associated proteintau, which is responsible for the neurofibrillary tangles in the brain associated with Alzheimers disease and other dementias. Koob is making full gene replacement mouse models of other neurodegenerative diseases.

Our philosophy is to make our mouse strains available to the research community in an expedited way, Koob said. I contacted JAX about this ACE2 receptor gene replacement mouse. Theyre very happy to collaborate with us because they dont have anything like this. And were making it available to researchers without restrictions.

With Koob and his laboratory scientist Kellie Benzow as inventors, the University has filed a patent onMethods of full gene replacement and transgenic non-human cells comprising full human genes.

Its been a long time since Koob collaborated with his graduate adviser Waclaw Szybalski, now a 98-year-old professor emeritus. Together their research careers encompass the history of molecular biology going back to the early 1950s with the discovery of the DNA double helix. Szybalski was born in 1921 just after a pandemic virus infected an estimated one-third of the Earths population and killed tens of millions of people. A century later, with another pandemic raging, the timing couldnt be better for his student to exercise his manifest molecular inventiveness.

William Hoffman is a writer and editor at the University of Minnesota. He has worked closely with faculty in genetics and bioengineering, medical technology and bioscience industries, and the science policy and ethics communities. He is author with Leo Furcht of Divergence, Convergence, and Innovation: East-West Bioscience in an Anxious Age, Asian Biotechnology and Development Review, Nov. 2014.

A version of this article was originally published at the University of Minnesota website and has been republished here with permission. The University of Minnesota can be found on Twitter @UMNews

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Genetic puzzle: How mice can be modified to help in the race to develop coronavirus therapies - Genetic Literacy Project

The genetic basis of bats’ superpowers revealed – Newswise

Newswise For the first time, the raw genetic material that codes for bats' unique adaptations and superpowers such as the ability to fly, to use sound to move effortlessly in complete darkness, to survive and tolerate deadly diseases, to resist ageing and cancer - has been fully revealed.

Bat1K (Bat1K.com), a global consortium of scientists dedicated to sequencing the genomes of every one of the 1421 living bat species, has generated and analyzed six highly accurate bat genomes that are ten times more complete than any bat genome published to date, in order to uncover bats' unique traits.

"Given these exquisite bat genomes, we can now better understand how bats tolerate viruses, slow down ageing, and have evolved flight and echolocation. These genomes are the tools needed to identify the genetic solutions evolved in bats that ultimately could be harnessed to alleviate human ageing and disease," Emma Teeling, University College Dublin, Co-Founding Director of Bat1K and Senior Author.

To generate these exquisite bat genomes, the team used the newest technologies of the DRESDEN-concept Genome Center, a shared technology resource in Dresden, to sequence the bat's DNA, and generated new methods to assemble these pieces into the correct order and to identify the genes present.

"Using the latest DNA sequencing technologies and new computing methods for such data, we have 96 to 99 percent of each bat genome in chromosome level reconstructions - an unprecedented quality akin to for example the current human genome reference which is the result of over a decade of intensive "finishing" efforts. As such, these bat genomes provide a superb foundation for experimentation and evolutionary studies of bats' fascinating abilities and physiological properties" Eugene Myers, Director of Max Planck Institute of Molecular Cell Biology and Genetics, and the Center for Systems Biology, Dresden, Germany, Senior Author.

Relationship to other mammals

The team compared these bat genomes against 42 other mammals to address the unresolved question of where bats are located within the mammalian tree of life. Using novel phylogenetic methods and comprehensive molecular data sets, the team found the strongest support for bats being most closely related to a group called Ferreuungulata that consists of carnivores (which includes dogs, cats and seals, among other species), pangolins, whales and ungulates (hooved mammals).

To uncover genomic changes that contribute to the unique adaptations found in bats, the team systematically searched for gene differences between bats and other mammals, identifying regions of the genome that have evolved differently in bats and the loss and gain of genes that may drive bats' unique traits.

"Our genome scans revealed changes in hearing genes that may contribute to echolocation, which bats use to hunt and navigate in complete darkness. Furthermore, we found expansions of anti-viral genes, unique selection on immune genes, and loss of genes involved in inflammation in bats. These changes may contribute to bats' exceptional immunity and points to their tolerance of coronaviruses." Michael Hiller, Max Planck Research Group Leader, Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Max Planck Institute for the Physics of Complex Systems, and the Center for Systems Biology, Dresden, Senior Author.

Tolerance against viruses

The team also found evidence that bats' ability to tolerate viruses is reflected in their genomes. The exquisite genomes revealed "fossilised viruses", evidence of surviving past viral infections, and showed that bat genomes contained a higher diversity than other species providing a genomic record of historical tolerance to viral infection.

Given the quality of the bat genomes the team uniquely identified and experimentally validated several non-coding regulatory regions that may govern bats' key evolutionary innovations.

"Having such complete genomes allowed us to identify regulatory regions that control gene expression that are unique to bats. Importantly we were able to validate unique bat microRNAs in the lab to show their consequences for gene regulation. In the future we can use these genomes to understand how regulatory regions and epigenomics contributed to the extraordinary adaptations we see in bats," says Sonja Vernes, Co-Founding Director Bat 1K, Max Planck Institute for Psycholinguistics, Nijmegen, Senior Author.

This is just a beginning. The remaining ~1400 living bat species exhibit an incredible diversity in ecology, longevity, sensory perception and immunology, and numerous questions still remain regarding the genomic basis of these spectacular features. Bat1K will answer these questions as more and more exquisite bat genomes are sequenced, further uncovering the genetic basis of bats' rare and wonderful superpowers.

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The genetic basis of bats' superpowers revealed - Newswise

Inside the Global Quest to Trace the Origins of COVID-19and Predict Where It Will Go Next – TIME

It wasnt greed, or curiosity, that made Li Rusheng grab his shotgun and enter Shitou Cave. It was about survival. During Mao-era collectivization of the early 1970s, food was so scarce in the emerald valleys of southwestern Chinas Yunnan province that farmers like Li could expect to eat meat only once a yearif they were lucky. So, craving protein, Li and his friends would sneak into the cave to hunt the creatures they could hear squeaking and fluttering inside: bats.

Li would creep into the gloom and fire blindly at the vaulted ceiling, picking up any quarry that fell to the ground, while his companions held nets over the mouth of the cave to snare fleeing bats. They cooked them in the traditional manner of Yunnans ethnic Yi people: boiled to remove hair and skin, gutted and fried. Theyd be small ones, fat ones, says Li, now 81, sitting on a wall overlooking fields of tobacco seedlings. The meat is very tender. But Ive not been in that cave for over 30 years now, he adds, shaking his head wistfully. They were very hard times.

China today bears little resemblance to the impoverished nation of Lis youth. Since Deng Xiaoping embraced market reforms in 1979, the Middle Kingdom has gone from strength to strength. Today it is the worlds No. 2 economy and top trading nation. It has more billionaires than the U.S. and more high-speed rail than the rest of the world combined. Under current strongman President Xi Jinping, China has embarked on a campaign to regain center place in the world. Farmers like Li no longer have to hunt bats to survive.

That doesnt mean Shitou Cave has faded in significance. Today, though, its musty depths speak not to local sustenance but global peril. Shitou was where Shi Zhengli, lead scientist at the Wuhan Institute of Virology (WIV), working with samples of bat feces in 2011 and 2012, isolated a novel virus that was very similar to SARS, which had been responsible for a pandemic a decade earlier. Shiknown as Chinas bat woman for her tireless research on the winged mammalwarned that other bat-borne diseases could easily spill over into human populations again. Seven years later, her fears appear vindicated. In a February paper, Shi revealed the discovery of what she called the closest relative of what would become known as SARS-CoV-2, the coronavirus that causes COVID-19. It also originated in Shitou Cave.

Dubbed RaTG13, Shis virus has a 96.2% similarity with the virus that has claimed some 600,000 lives across the world, including more than 140,000 in the U.S. Shis discovery indicates COVID-19 likely originated in batsas do rabies, Ebola, SARS, MERS, Nipah and many other deadly viruses.

But how did this virus travel from a bat colony to the city of Wuhan, where the coronavirus outbreak was first documented? And from there, how did it silently creep along motorways and flight routes to kill nurses in Italy, farmers in Brazil, retirees in Seattle? How this virus entered the human population to wreak such a devastating toll is the foremost issue of global scientific concern today. The search for patient zeroor the index case, the first human COVID-19 infectionmatters. Not because any fault or blame lies with this individual, but because discovering how the pathogen entered the human population, and tracing how it flourished, will help the science and public-health communities better understand the pandemic and how to prevent similar or worse ones in the future.

On top of the millions of lives that hang in the balance, Cambridge University puts at $82 trillion across five years the cost to the global economy of the current pandemic. The human race can ill afford another.

The provenance of COVID-19 is not only a scientific question. The Trump Administration also regards it as a political cudgel against Beijing. As the U.S. has failed to control outbreaks of the coronavirus and its economy founders, President Donald Trump has deflected blame onto China.

Trump and senior Administration figures have dubbed COVID-19 the China virus and Wuhan virus. Secretary of State Mike Pompeo said there was enormous evidence the virus had escaped from Shis lab in the city. (He has yet to share any hard evidence.) This is the worst attack weve ever had on our country. This is worse than Pearl Harbor. This is worse than the World Trade Center, Trump said in May of the pandemic, pointing the finger at China. In response, Chinese Foreign Minister Wang Yi accused the U.S. President of trying to foment a new cold war through lies and conspiracy theories.

The origin of the virus is clearly a touchy subject. Nevertheless, the world desperately needs it broached. Australia and the E.U. have joined Washingtons calls for a thorough investigation into the cause of the outbreak. On May 18, Xi responded to pressure to express support for global research by scientists on the source and transmission routes of the virus overseen by the World Health Organization.

But Trump has already accused the WHO of being Chinacentric and vowed to stop funding it. His attacks may have some basis in fact. The organization refused self-governing Taiwan observer status under pressure from Beijing. And privately, WHO officials were frustrated by the slow release of information from the Chinese authorities even as they publicly praised their transparency, according to transcripts obtained by the Associated Press.

Partisan bickering and nationalism threaten to eclipse the invaluable scientific work required to find the true source of the virus. Time is of the essence; a SARS vaccine was within touching distance when research that could have proved invaluable today was discontinued as the crisis abated. Once this pandemic settles down, were going to have a small window of opportunity to put in place infrastructure to prevent it from ever happening again, says Dr. Maureen Miller, a Columbia University epidemiologist.

The search for the viruss origins must begin behind the squat blue-shuttered stalls at Wuhans Huanan seafood market, where the outbreak of viral pneumonia we now know as COVID-19 was first discovered in mid-December. One of the first cases was a trader named Wei Guixian, 57, who worked in the market every day, selling shrimp out of huge buckets. In mid-December she developed a fever she thought was a seasonal flu, she told state-run Shanghai-based the Paper. A week later, she was drifting in and out of consciousness in a hospital ward.

Of the first 41 patients hospitalized in Wuhan, 13 had no connection to the marketplace, including the very first recorded case. That doesnt necessarily excuse the market as the initial point of zoonotic jump, thoughwe dont know yet for certain how many COVID-19 cases are asymptomatic, but research suggests it could be as high as 80%. And, even if Huanan market wasnt where the virus first infected humans, it certainly played a huge role as an incubator of transmission. At a Jan. 26 press conference, the Hong Kong Centre for Health Protection revealed 33 of 585 environmental samples taken after the market was shut Jan. 1 tested positive for the virus. Of these, 31 were taken in the western section where wildlife was sold.

In May, China acceded to demands for an independent inquiry after more than 100 countries supported a resolution drafted by the E.U. Still, President Xi insists it must be comprehensivelooking not just at China but also at how other nations responded to the WHOs warningsand cannot begin until after the pandemic has subsided. The principles of objectivity and fairness need to be upheld, Xi told the World Health Assembly. (Notably, inquiries into the 2009 H1N1 swine flu pandemic and 2014 West African Ebola outbreak began before the crises had abated.) According to past investigations protocols, teams are composed of independent public-health experts and former WHO staff appointed by the WHO based on member states recommendations. At a practical level, however, any probe within China relies on cooperation from Beijing, and its uncertain whether the U.S. will accept the findings of a body Trump has slammed for severely mismanaging and covering up the spread of the coronavirus.

Peter Ben Embarek, a food-safety and animal-disease expert at the WHO, says an investigation must concentrate on interviews with all the initial cases, trying to find clues about potential earlier infections among their relatives, their contacts, and where they had been over the days and weeks before they got sick. Also, which hunters and farmers supplied what species of animals. With a bit of luck and good epidemiological work, it can be done, he says.

Artwork by Brea Souders for TIME; Shutterstock (3)

There are many who look at where COVID-19 emerged and see something that cant be just a co-incidence. In 2017, China minted its first biosecurity-level 4 (bsl-4) laboratorythe highest level cleared to even work with airborne pathogens that have no known vaccinesin Wuhan. Ever since, the countrys foremost expert on bat viruses has been toiling away inside the boxy gray buildings of the WIV. Indeed, when Shi first heard about the outbreak, she herself thought, Could they have come from our lab? she recently told Scientific American. An inventory of virus samples reassured her that it hadnt, she added, yet that hasnt stopped some from maintaining their suspicions.

Mistakes do happen. The last known case of small-pox leaked from a U.K. laboratory in 1978. SARS has leaked from Chinese laboratories on at least two occasions, while U.S. scientists have been responsible for mishandlings of various pathogens, including Ebola. There are only around 70 bsl-4 laboratories in 30 countries. Suspicions regarding the nature of research under way inside the Wuhan laboratory persist. According to one leading virologist, who asked to remain anonymous for fear of jeopardizing funding and professional relationships, Were you to ask me wheres the most likely place in the world for a naturally occurring bat coronavirus to escape from a laboratory, Wuhan would be in the top 10.

Still, neither the WHO nor the Five Eyes intelligence networkcomprising the U.S., U.K., Canada, Australia and New Zealandhas found evidence that COVID-19 originated from Shis lab. Canberra has even distanced itself from a U.S.-authored dossier that sought to convince the Australian public that the Five Eyes network had intelligence of a Chinese cover-up. (It appeared to rely exclusively on open-source material.) Meanwhile, scientific peers have rallied to defend Shi from suspicion. She is everything a senior scientist should be, says Miller, who has collaborated with Shi on various studies. The Wuhan Institute of Virology did not respond to requests for comment.

Available evidence suggests COVID-19 leaped from wild animal to human. Tracing exactly how is crucial. It enables governments to install safeguards regarding animal husbandry and butchery to prevent any repeat. SARS, for example, originated in bats and then infected a palm civet, a catlike mammal native to South and Southeast Asia. The animal was then sold at a wet marketwhere fresh meat, fish and sometimes live animals are soldin Guangdong, from which it jumped to humans. In the wake of that outbreak, which claimed at least 774 lives worldwide, palm civets were banned from sale or consumption in China. Bats may have been the initial reservoir for SARS-CoV-2, but its likely that there was an intermediary before it got to humans, and thats where the possibilities grow. Bats share Shitou Cave with starlings, for one, and at least one large white owl nests in its upper reaches. Herds of black and white goats graze the dusty shrub all around the cave opening, while the Yi ethnic group traditionally rear and eat dogs. Bat guano is also traditionally prized as a fertilizer on crops.

Just a few miles from Shitou, customers at Baofeng Horse Meat restaurant squat by round tables, slurping green tea poured from enormous brass teapots, while charcoal burners cook up the eponymous cuts alongside dogmeat and other specialties. All the animals we sell are reared nearby, says proprietor Wang Tao. Cultural practices and disease-transmission vectors are often entwined. MERS continues to jump between camels and their human handlers on the Arabian Peninsula. Chinas penchant for eating rare and unusual wildlife for obscure health benefits may have contributed to the current pandemic. While many aspects of Traditional Chinese Medicine (TCM) are entirely benign, involving little more than massage, pressure points and bitter herbs, there is a fetishization of exotic animals, and theres some evidence that TCM might have played a role in launching the pandemic. The receptor-binding domain of SARS-CoV-2s spike proteinwhich the virus uses to bind to hostsis unusually adept at attaching to human cells. New viruses discovered in Malaysian pangolins have since been shown to have exactly the same receptor binders. Some features in [SARS-CoV-2] that initially may have looked unusual, youre now finding in nature, says Edward Holmes, an evolutionary biologist and virologist at the University of Sydney.

That COVID-19 originated in bats and then jumped to humans via a pangolin intermediary is now the most likely hypothesis, according to multiple studies (although some virologists disagree). Up to 2.7 million of the scaly mammals have been plucked from the wild across Asia and Africa for consumption mostly in China, where many people believe their scales can treat everything from rheumatoid arthritis to inflammation. Their meat is also highly prized for its supposed health benefits.

On Feb. 24, China announced a permanent ban on wildlife consumption and trade, scratching out an industry that employs 14 million people and is worth $74 billion, according to a 2017 report commissioned by the Chinese Academy of Engineering. Its again extremely sensitive. President Xi is an ardent supporter of TCM and has promoted its use globally. The total value of Chinas TCM industry was expected to reach $420 billion by the end of this year, according to a 2016 white paper by Chinas State Council. And rather than raising the possibility that misuse of TCM sparked the outbreak, Chinese state media has laudedwithout evidencethe critical role TCM has played in the treatment of COVID-19 patients. In an apparent attempt to head off criticism related to the pandemic, draft legislation was published in late May to ban any individual or organization from defaming or making false or exaggerated claims about TCM. Cracking down on the illicit animal trade would go a long way toward preventing future outbreaks. But as demand for meat grows across increasingly affluent Asia, Africa and Latin America, the potential for viruses to spill over into human populations will only increase.

It probably wasnt blind luck that Li and his friends didnt get sick from their hunting expeditions in Shitou Cave. Research by Columbias Miller with WIVs Shi, published in 2017, found that local people were naturally resistant to SARS-like viruses. Examining their lifestyle habits and antibodies can help deduce both mitigating factors and possible therapies, while pinpointing which viruses are particularly prone to infecting humans, potentially allowing scientists to design vaccines in advance. They are the canaries in the coal mine, says Miller.

The cloud of uncertainty surrounding the viruss origins may never lift. Identifying an individual patient zero where the virus made the jump from animal to human may be rendered impossible by its remarkable ability to spread while asymptomatic. But just as important is uncovering the broader map of how the virus spread and changed genetically as it did so. In theory, that sort of genetic surveillance could foster the development of broad-spectrum vaccines and antivirals that may prove effective against future novel outbreaks. Studying the anatomy of viruses that readily jump between species may even help predict where the next pandemic is coming from, and prepare us for the inevitable next time. So did those of his 40-member team of infectious-disease emergency responders at Providence Regional Medical Center in Everett, Wash. The first time, the alert was part of a routine monthly test. This time, it was the real thing.

The page signaled the first confirmed U.S. case of COVID-19. The patient was a Washington State resident who had recently returned from visiting family in Wuhan, where the disease was spreading rapidly. Aware of his higher risk, and concerned when he developed a fever, the 35-year-old (who wishes to remain anonymous) visited an urgent-care center where he told health care providers about his travel history. They notified the state health department, which in turn helped the care center send a sample for testing to the Centers for Disease Control and Prevention (CDC) in Atlantaat the time, the only labs running COVID-19 tests. When the test was positive, CDC scientists recommended the patient be hospitalized for observation. And Diazs team was paged.

A trained ambulance team arrived at the mans home, moved him into a specially designed mobile isolation unit, and drove 20 minutes to Providence Regional. There, the patient couldnt see who greeted him; everyone assigned to his care was garbed in layers of personal protective equipment. Once in his room, he spoke to medical staff only through a tele-health robot equipped with a screen that displayed their faces, transmitted from just outside the room.

A nurse carefully swabbed the back of his nose and pharynx for a sample of the virus that had brought him to the hospital. Not only was he the first confirmed case of COVID-19 in the U.S., he was also the first in the country to have his virus genetically sequenced. As the index patient in the U.S., his sequence, named WA1 (Washington 1), served as the seed from which experts would ultimately trace the genetic tree describing SARS-CoV-2s path from person to person across communities, countries and the globe, as it mutated and either died out or moved on with renewed vigor to infect more people.

Genetic sequencing is a powerful tool to combat viruses fondness for mutating. Viruses are exploitative and unscrupulous; they dont even bother investing in any of their own machinery to reproduce. Instead, they rely on host cells to do thatbut it comes at a price. This copying process is sloppy, and often leads to mistakes, or mutations. But viruses can sometimes take advantage of even that; some mutations can by chance make the virus more effective at spreading undetected from host to host. SARS-CoV-2 seems to have landed on at least one such suite of genetic changes, since those infected can spread the virus even if they dont have any symptoms.

Figuring out how to map those changes is a fairly new science. Following the 2014 West African outbreak of Ebola, scientists mapped the genomes of about 1,600 virus samples, collected from the start of the outbreak and representing about 5% of total cases. The work offered insights into how Ebola moved between locations and mutated. But it wasnt published until 2017, because the majority of the sequencing and sharing of that data was done after the diseases peak, says Trevor Bedford, associate professor at the Fred Hutchinson Cancer Research Center and co-founder of Nextstrain.org, an open-source database of SARS-CoV-2 genetic sequences. With COVID-19, everything is happening much more quickly, he says, which makes the information more immediately useful.

Since the first SARS-CoV-2 genome was published and made publicly available online in January, scientists have mapped the genomes of over 70,000 (and counting) samples of the virus, from patients in China, the U.S., the E.U., Brazil and South Africa, among others. They deposited those sequences into the Global Initiative on Sharing All Influenza Data (GISAID), a publicly available genetic database created in 2008 initially to store and share influenza genomes. During the coronavirus pandemic, it has quickly pivoted to become a clearinghouse for tracking the genetics of SARS-CoV-2, enabling scientists to map the viruss march across continents and detail its multipronged attack on the world.

We have genomes from researchers and public-health labs from all over the world on six continents, says Joel Wertheim, associate professor of medicine at University of California, San Diego. It provides us with unique insight and confidence that other types of epidemiological data just cannot supply. Relying on the GISAID sequences, Nextstrain has become a virtual watering hole for scientistsand increasingly public-health officialswho want to view trends and patterns in the viruss genetic changes that can help inform decisions about how to manage infections.

If genetic sequencing is the new language for managing infectious-disease outbreaks, then the mutations that viruses generate are its alphabet. If paired with information on how infected patients fare in terms of their symptoms and the severity of their illness, genomic surveillance could reveal useful clues about which strains of virus are linked to more severe disease. It might shed light on the mystery of why certain victims of the virus are spared lengthy hospital stays and life-threatening illness. As nations start to reopen, and before a vaccine is widely available, such genetic intel could help health care providers to better plan for when and where they will need intensive-care facilities to treat new cases in their community.

Genetic information is also critical to developing the most effective drugs and vaccines. Knowing the sequence of SARS-CoV-2 enabled Moderna Thera-peutics to produce a shot ready for human testing in record time: just two months from when the genetic sequence of SARS-CoV-2 was first posted. Even after a vaccine is approved and distributed, continuing to track genetic changes in SARS-CoV-2 to ensure its not mutating to resist vaccine-induced immunity will be critical. The data collected by Nextstrain will be crucial to help vaccine researchers tackle mutations, potentially for years to come. Already, the group advises the WHO on the best genetic targets for the annual flu shot, and it plans to do the same for COVID-19. We can track the areas of the virus targeted by the vaccine, and check the mutations, says Emma Hodcroft from the University of Basel, who co-developed Nextstrain. We can predict how disruptive those mutations are to the vaccine or not and tell whether the vaccines need an update.

Meanwhile, genetic surveillance provides real-time data on where the virus is going and how its changing. This is the first time during an outbreak that lots of different researchers and institutes are sharing sequencing data, says Barbara Bartolini, a virologist at the Lazzaro Spallanzani National Institute for Infectious Diseases in Rome, who has sequenced dozens of viral samples from patients in Italy. That information is giving public-health experts more precise information on the whereabouts of its viral enemy that no traditional disease-tracking method can supply.

After Diazs patient tested positive for SARS-CoV-2, Washington State public-health officials diligently traced the places the patient had been and the people hed come in contact with. He had taken a ride-share from the airport, gone to work and enjoyed lunch at a seafood restaurant near his office with colleagues. But because so little was known about the virus at the time, these contact tracers were focusing mostly on people with symptoms of illnessand at the time, none of the patients contacts reported them. The genetics, however, told a different story.

Seattle happened to have launched a program in 2018 to track flu cases by collecting samples from patients in hospitals and doctors offices, sites on college campuses, homeless shelters, the citys major international airport and even from volunteers with symptoms who agreed to swab their nasal passages at home. Those that were positive for influenza and other respiratory illnesses had their samples genetically sequenced to trace the diseases spread in the community. As COVID-19 began to emerge in the Seattle area at the end of February, Bedford and his colleagues began testing samples collected in this program for SARS-CoV-2, regardless of whether people reported symptoms or travel to China, then the worlds hot spot for the virus. Thats how they found WA2, the first case in Washington that wasnt travel-related. By comparing samples from WA1, WA2 and other COVID-19 cases, they figured out that SARS-CoV-2 was circulating widely in the community in February.

If that community-based sequencing work had been conducted earlier, theres a good chance it might have picked up cases of COVID-19 that traditional disease-tracking methods, which at the time focused only on travel history and symptoms, missed. That would have helped officials make decisions about a lockdown sooner, and might have helped to limit spread of the virus. SARS-CoV-2 moves quickly but mutates relatively slowly, for a virusgenerating only about two mutations every month in its genome. For drug and vaccine developers, it means the virus can still evade new treatments designed to hobble it. Those same changes serve as passport stamps for its global trek through the worlds population, laying out the itinerary of the viruss journey for geneticists like Bedford. The cases in the initial Seattle cluster, he says, appear to have all been connected, through a single introduction directly from China to the U.S. in mid- to late January. Until the end of February, most instances of SARS-CoV-2 in the U.S. piggybacked on unwitting travelers from China. But as the pandemic continued, that changed.

Genetic analysis confirmed that on Feb. 26, SARS-CoV-2 had already hit a new milestone, with the first documented case that it had successfully jumped to a new host in Santa Clara, Calif., one with no travel history to the infectious-disease hot spots in China or known contact with anyone who had traveled there. Its not clear how this person got infected, but genetic sequencing showed this patient passed on the virus to two health care workers while being treated in the hospitaland that the virus was already spreading in the community, without help from imported cases.

Bedfords team began to see mutations in samples from Seattle that matched samples from people in Europe and the U.S.s East Coast. At the beginning we could kind of draw a direct line from viruses circulating in China to viruses circulating in the Seattle area, says Bedford. Later, we see that viruses collected from China have some mutations that were seen later in Europe, and those same mutations were seen in viruses in New York. So, we can draw another line from China to Europe to New York and then on to Seattle. The virus had begun multiple assaults into the U.S.

TIME Graphic by Emily Barone and Lon Tweeten

Around the world, virologists were seeing similar stories written in the genes of SARS-CoV-2. In January, a couple from Hubei province arrived in Rome, eager to take in the sights of the historic European city. By Jan. 29, they were hospitalized at Lazzaro Spallanzani National Institute for Infectious Diseases with fever and difficulty breathing. Tests confirmed they were positive for SARS-CoV-2.

Bartolini, a virologist at the hospital, and her colleagues compared the genetic sequences from a sample taken from the wife to sequences posted on GISAID. The Italian researchers found it matched five other samples from patients as far-flung as France, Taiwan, the U.S. and Australia. SARS-CoV-2 was clearly already on a whirlwind tour of the planet.

Not all strains of SARS-CoV-2 are equally virulent; some branches of its genetic tree are likely to grow larger and sprout further offshoots, while others terminate more quickly, says Harm van Bakel, assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai. His team conducted the first genetic sequencing analysis of cases in New York City, which quickly became a U.S. hot spot; by March the city had seen a half a dozen or so separate introductions of SARS-CoV-2, but only two resulted in massive spread of the virus. The remainder petered out without transmitting widely.

Retrospectively, theres no way to tell for sure if these two strains were simply in the right place at the right timein a particularly densely populated area of the city, for example, or in an area where people congregated and then dispersed to other parts of the cityor if they were actually more infectious. But determining the genetic code of a circulating virus early may help scientists and governments decide which strains are worth worrying about and which arent.

From analyzing genetic sequences from 36 samples of patients in Northern California, Dr. Charles Chiu, professor of laboratory medicine and infectious diseases at the University of California, San Francisco, says it might have been possible to identify the major circulating strains and track how they spread if more testing were available to know who was infectedand use this information to guide quarantine and containment practices. There was a window of opportunity that if we had more testing and more contact-tracing capacities available early on, we likely would have prevented the virus from gaining a foothold at least in California, he says.

There were similar missed opportunities in Chicago, where genetic sequencing of 88 viruses revealed that the outbreak resulted from three main strains. One was similar to those circulating in New York; one was closely related to the Washington cases and a third never spread appreciably outside the Chicago area. This suggests that stricter travel restrictions might have helped limit introduction of the virus and transmission in northern Illinois.

Ongoing genetic sequencing can also help officials tailor narrower strategies to quell the spread of a virus. It wasnt long after Beijing reopened following two months of lockdown that infections began creeping up again in June. Sequencing of the new cases revealed that the viruses circulating at the time shared similarities with viruses found in patients in Europe, suggesting the cases were new introductions of SARS-CoV-2 and not lingering virus from the original outbreak. That helped the Chinese government decide to implement only limited lockdowns and testing of people in specific apartment blocks around a food market where the cluster of cases emerged, rather than resort to a citywide quarantine.

And there are other, less obvious ways that genetic analysis of SARS-CoV-2 could help to predict surges in cases as people emerge from lockdown. Italian scientists have sampled wastewater from sewage treatment plants in northern cities where the pandemic flourished, and found evidence of SARS-CoV-2 weeks before the first cases showed up to flood the hospitals. In La Crosse, Wis., Paraic Kenny, director of the Kabara Cancer Research Institute of the Gundersen Health System, applied the same strategy in his hometown in the spring. A few weeks later, in mid-June, when cases of COVID-19 surged because of bars reopening in downtown La Crosse, Kenny compared samples from infected people with the viral genomes in his wastewater samples. They were a genetic match. The same strain of SARS-CoV-2 had been circulating in the community weeks before the cases were reported. In principle, an approach like this can be used to not just ascertain how much virus is in the community, but maybe give hospitals and public-health departments a warning of when to anticipate a surge in cases, he says. The goal is to know not just where we are today but where we will be a week or two from now.

It has been 100 years since an infectious disease pushed the entire worlds population into hiding to the extent that COVID-19 has. And the primary approaches we take to combatting emerging microbes today are likewise centuries old: quarantine, hygiene and social distancing. We may never learn exactly where SARS-CoV-2 came from, and its clearly too late to prevent it from becoming a global tragedy. But extraordinary advances in scientific knowledge have given us new tools, like genetic sequencing, for a more comprehensive understanding of this virus than anyone could have imagined even a decade or two ago. These are already providing clues about how emerging viruses like SARS-CoV-2 operate and, most important, how they can be thwarted with more effective drugs and vaccines.

This knowledge can save millions of livesas long as science leads over politics. As unprecedented as this pandemic seems, in both scope and speed, it shouldnt have caught the world by surprise. For decades, scientific experts have been warning that emerging zoonotic viruses are a threat to humanity of the greatest magnitude. People keep using the term unprecedented. Ill tell you, biologically, there is nothing unprecedented about this virus really, says Holmes, the evolutionary biologist. Its behaving exactly as I would expect a respiratory virus to behave. Its simply how viruses work, have always worked and will continue to work. The sooner we accept that, the sooner we can act on that knowledge to control outbreaks more quickly and efficiently.

With reporting by Jamie Ducharme/New York, Madeline Roache/London and John Walcott/Washington

This appears in the August 03, 2020 issue of TIME.

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Inside the Global Quest to Trace the Origins of COVID-19and Predict Where It Will Go Next - TIME

Baylor Genetics and the City of Houston Form COVID-19 Testing Partnership – PRNewswire

HOUSTON, July 23, 2020 /PRNewswire/ --In response to the global pandemic, Baylor Genetics, a pioneer in genetic testing and precision medicine, launched its official test for COVID-19 on June 16, 2020. To help prevent the spread of COVID-19 in Houston, Texas, Baylor Genetics has partnered with the Houston Health Department, City of Houston (COH), to provide quality, high-throughput testing for COVID-19.

"With this partnership, the City of Houston and Baylor Genetics are able to work together and help our city overcome this pandemic," said Kengo Takishima, President and Chief Executive Officer for Baylor Genetics. "By continuing to focus on innovation, we are able to serve our city by providing insight on this virus and help restore our local communities."

This partnership entails quick and efficient testing for COH, which will help the city monitor future outbreaks and provide valuable data for steps needed to prevent the spread in Houston communities.

"We are grateful to have Baylor Genetics as an additional laboratory resource," said Stephen L. Williams, Director of the Houston Health Department. "With nearly 200,000 people tested for COVID-19 at Houston Health Department-affiliated testing sites, it's important to plan ahead for adequate laboratory capacity as we continue working to slow the spread of this deadly virus."

While Baylor Genetics' main focus has been genetic testing of inherited disorders and cancer, the diagnostic company was quickly able to validate a test for COVID-19 in its high-complexity CLIA-certified, CAP-accredited laboratory. Per the Centers for Disease Control and Prevention, the methodology used by Baylor Genetics for its COVID-19 (SARS-CoV-2) RT-PCR test is the principle standard for detecting if an individual is infected with the novel coronavirus, SARS-CoV-2.

"At Baylor Genetics, we are committed to improving healthcare globally and locally no matter if that involves testing for genetic disorders or testing for infectious diseases," said Christine Eng, MD, Chief Medical Officer and Chief Quality Officer at Baylor Genetics and Professor of Molecular and Human Genetics at Baylor College of Medicine. "With our state-of-the-art molecular processes, the launch of our COVID-19 test is poised to help thousands determine if they are infected with SARS-CoV-2. Our goal is to give patients in Houston fast and reliable results, so they can receive the treatment they need early on and flatten the spread of the infection in our community."

To learn more about Baylor Genetics' test for COVID-19, visit https://www.baylorgenetics.com/covid-19-testing.

AboutBaylor Genetics:Baylor Genetics is a joint venture of H.U. Group Holdings, Inc. and Baylor College of Medicine, including the #1 NIH-funded Department of Molecular and Human Genetics. Located in Houston's Texas Medical Center, Baylor Genetics serves clients in 50 states and 16 countries.

Learn more about Baylor Genetics atwww.baylorgenetics.com

Media Contact:Jamie LimEmail: [emailprotected]

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Triplet Therapeutics Appoints Alan Buckler, Ph.D., as Chief Scientific Officer – Business Wire

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Triplet Therapeutics, Inc., a biotechnology company leveraging insights from the human genetics of repeat expansion disorders (REDs), today announced the appointment of Alan Buckler, Ph.D., as its chief scientific officer. Dr. Buckler joins Triplet from Scholar Rock, where he served as chief scientific officer and helped drive two product candidates from discovery to the clinic.

We are delighted to welcome Alan to Triplet, said Nessan Bermingham, Ph.D., founder, president, and CEO of Triplet. His foundational understanding of the genetic basis for REDs and his extensive experience in R&D complements our existing management team, our deep understanding of a novel pathway in REDs, and the R&D strategy for our thRED Engine, from which our recently announced clinical candidate TTX-3360 was identified. We are rapidly advancing therapies that could be transformative for patients with REDs and expect to file an IND in the second half of 2021.

Dr. Buckler has over 25 years of leadership and research experience in drug discovery. Prior to Scholar Rock, he served as vice president, cell and protein sciences at Biogen, and spent nine years leading drug discovery programs at Novartis Institutes of Biomedical Research. He has also held senior scientific leadership positions at Axys Pharmaceuticals (formerly Sequana Therapeutics), leaving as vice president, molecular genetics.

Dr. Buckler has a longstanding interest and commitment to understanding and treating REDs. Early in his career, he worked on Huntingtons disease a highly prevalent and severe RED with Jim Gusella, Ph.D., Bullard Professor of Neurogenetics at Harvard Medical School and a member of Triplets scientific advisory board, whose pioneering work helped establish the genetic cause of the disease and later identified genetic modifiers.

As a postdoctoral fellow in the laboratory of Dr. David Housman at the Massachusetts Institute of Technology (MIT), Dr. Buckler was part of the collaborative efforts that led to the discovery of both the Huntingtons disease and myotonic dystrophy genes as well as the underlying repeat expansions that cause these diseases. Dr. Buckler serves on the Scientific Advisory Board of the Hereditary Disease Foundation, a nonprofit organization committed to funding innovative research into treatments for Huntingtons disease and other brain disorders.

Dr. Bucklers other areas of therapeutic expertise include neurologic and metabolic disorders, cancer, fibrosis, and inflammatory diseases. He was a member of the neurology faculty at Massachusetts General Hospital/Harvard Medical School, and also served as a research staff member at MIT and Boston University before joining the private sector. Dr. Buckler received his Bachelor of Arts from the University of Chicago and his Ph.D. in Microbiology from the Boston University School of Medicine. He completed his postdoctoral training at MIT.

Grounded in human genetics, Triplets approach is uniquely designed to target a fundamental driver of repeat expansion disorders, said Dr. Buckler. I am excited to join this first-class team as we work to advance innovative therapies for patients living with these devastating diseases.

About TTX-3360TTX-3360, an antisense oligonucleotide, is the first clinical candidate developed from Triplets proprietary thRED Engine and the first therapeutic candidate with the potential to modify the course of REDs by targeting the DNA Damage Response (DDR) pathway. A significant body of evidence supports the role of the DDR pathway as the primary driver of repeat expansion and subsequent disease onset and progression in many REDs, including Huntingtons disease (HD), myotonic dystrophy (DM1) and fragile X syndrome. Triplet is initially focusing development of TTX-3360 in HD and may also evaluate it in other central nervous system indications such as spinocerebellar ataxias, fragile X syndrome, and familial amyotrophic lateral sclerosis (ALS).

About Triplet TherapeuticsTriplet Therapeutics is a biotechnology company developing transformational treatments for patients with repeat expansion disorders (REDs) a group of more than 50 known genetic diseases including Huntingtons disease, myotonic dystrophy, spinocerebellar ataxias, fragile X syndrome, and familial amyotrophic lateral sclerosis (ALS) leveraging insights from patient genetics. Triplet designs and develops potential therapeutics for REDs using its proprietary thRED Engine, which enables the Company to develop a single oligonucleotide targeting the DNA Damage Response (DDR) pathway to potentially treat multiple REDs.

Triplet is backed by investments from Atlas Venture, MPM Capital and Pfizer Ventures, along with Invus, Partners Innovation Fund and Alexandria Venture Investments. Triplet is headquartered in Cambridge, Mass. For more information, please visit http://www.triplettx.com.

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The genetic basis of bats superpowers revealed – YubaNet

July 23, 2020 For the first time, the raw genetic material that codes for bats unique adaptations and superpowers such as the ability to fly, to use sound to move effortlessly in complete darkness, to survive and tolerate deadly diseases, to resist ageing and cancer has been fully revealed.

Bat1K (Bat1K.com), a global consortium of scientists dedicated to sequencing the genomes of every one of the 1421 living bat species, has generated and analyzed six highly accurate bat genomes that are ten times more complete than any bat genome published to date, in order to uncover bats unique traits.

Given these exquisite bat genomes, we can now better understand how bats tolerate viruses, slow down ageing, and have evolved flight and echolocation. These genomes are the tools needed to identify the genetic solutions evolved in bats that ultimately could be harnessed to alleviate human ageing and disease, Emma Teeling, University College Dublin, Co-Founding Director of Bat1K and Senior Author.

To generate these exquisite bat genomes, the team used the newest technologies of the DRESDEN-concept Genome Center, a shared technology resource in Dresden, to sequence the bats DNA, and generated new methods to assemble these pieces into the correct order and to identify the genes present.

Using the latest DNA sequencing technologies and new computing methods for such data, we have 96 to 99 percent of each bat genome in chromosome level reconstructions an unprecedented quality akin to for example the current human genome reference which is the result of over a decade of intensive finishing efforts. As such, these bat genomes provide a superb foundation for experimentation and evolutionary studies of bats fascinating abilities and physiological properties Eugene Myers, Director of Max Planck Institute of Molecular Cell Biology and Genetics, and the Center for Systems Biology, Dresden, Germany, Senior Author.

Relationship to other mammals

The team compared these bat genomes against 42 other mammals to address the unresolved question of where bats are located within the mammalian tree of life. Using novel phylogenetic methods and comprehensive molecular data sets, the team found the strongest support for bats being most closely related to a group called Ferreuungulata that consists of carnivores (which includes dogs, cats and seals, among other species), pangolins, whales and ungulates (hooved mammals).

To uncover genomic changes that contribute to the unique adaptations found in bats, the team systematically searched for gene differences between bats and other mammals, identifying regions of the genome that have evolved differently in bats and the loss and gain of genes that may drive bats unique traits.

Our genome scans revealed changes in hearing genes that may contribute to echolocation, which bats use to hunt and navigate in complete darkness. Furthermore, we found expansions of anti-viral genes, unique selection on immune genes, and loss of genes involved in inflammation in bats. These changes may contribute to bats exceptional immunity and points to their tolerance of coronaviruses. Michael Hiller, Max Planck Research Group Leader, Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Max Planck Institute for the Physics of Complex Systems, and the Center for Systems Biology, Dresden, Senior Author.

Tolerance against viruses

The team also found evidence that bats ability to tolerate viruses is reflected in their genomes. The exquisite genomes revealed fossilised viruses, evidence of surviving past viral infections, and showed that bat genomes contained a higher diversity than other species providing a genomic record of historical tolerance to viral infection.

Given the quality of the bat genomes the team uniquely identified and experimentally validated several non-coding regulatory regions that may govern bats key evolutionary innovations.

Having such complete genomes allowed us to identify regulatory regions that control gene expression that are unique to bats. Importantly we were able to validate unique bat microRNAs in the lab to show their consequences for gene regulation. In the future we can use these genomes to understand how regulatory regions and epigenomics contributed to the extraordinary adaptations we see in bats, says Sonja Vernes, Co-Founding Director Bat 1K, Max Planck Institute for Psycholinguistics, Nijmegen, Senior Author.

This is just a beginning. The remaining ~1400 living bat species exhibit an incredible diversity in ecology, longevity, sensory perception and immunology, and numerous questions still remain regarding the genomic basis of these spectacular features. Bat1K will answer these questions as more and more exquisite bat genomes are sequenced, further uncovering the genetic basis of bats rare and wonderful superpowers.

SEE ORIGINAL STUDY: https://www.nature.com/articles/s41586-020-2486-3

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The genetic basis of bats superpowers revealed - YubaNet

Fireflies help kindle new tests and treatments for COVID-19 – TMC News – Texas Medical Center News

Scientists at The University of Texas Medical Branch at Galveston (UTMB) have employed an unlikely partner in their quest to develop treatments for COVID-19 disease: the common firefly.

Fireflies, also known as lightning bugs, are insects in the Lampyridae family who use bioluminescence to attract potential mates and prey. Their conspicuous glow at twilight comes from an enzyme called luciferase, which can be isolated in the lab. Now, UTMB virologists are using the enzyme to develop faster and more accurate diagnostic tests for COVID-19 as well as to analyze potential therapies and gain a clearer understanding of the SARS-CoV-2 virus itself.

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We are very much interested in using basic research knowledge to develop systems to support translational work, for example, diagnosing disease, vaccine development, medical countermeasures and therapeutic drugsall those things that can be applied to the public health and human well-being, said Pei-Yong Shi, Ph.D., professor of human genetics in the department of biochemistry and molecular biology at UTMB. He is leading the research by labeling viruses with glowing tags like luciferase to study them.

Prior to the SARS-CoV-2 outbreak, Shis team had been focused on flaviviruses, including West Nile virus, Zika and dengue. His lab developed the first infectious clones of the epidemic strain of both West Nile and Zika and have established new pathways for flavivirus vaccine and drug discovery.

But as the COVID-19 pandemic swept the globe, Shis lab adapted by altering research techniques to address the SARS-CoV-2 virus.

First, researchers harnessed luciferase to develop faster diagnostic testing through innovative assaysinvestigative procedures that measure the activity or amount of a substance. The lab can now visually confirm the presence of antibodies that can block a SARS-CoV-2 infection earlier than through previous methods.

The great thing about luciferase, and the one that we specifically use which is nanoluciferase, is that its really bright, said Coleman Baker, a fourth-year graduate student in the department of microbiology and immunology at UTMB who works in the Shi lab. We found that these detection assays can be read earlier than most people thought. Most people would do these 24 to 48 hours after infection and we found that you can read them as early as 4 hours post-infection.

Not only does the enhanced brightness provided by luciferase decrease turnaround time for a diagnosis, but it also helps speed up the process of vaccine development.

For vaccine studies, you need to find out how much of a response somebody has to a potential vaccine, Baker said. So, instead of the traditional waywhich could take dayswe can get results in four hours after infection.

Shi said his team has been collaborating with leading pharmaceutical companies to help them evaluate their vaccine candidates, specifically by measuring the immune response in humans in clinical trials. His labs systembased on reporter viruses in which the luciferase enzyme is inserted into the virus genome to make it easy to followmeasures the concentration of neutralizing antibodies while also allowing for a much higher throughput. According to Xuping Xie, Ph.D., assistant professor in the department of biochemistry and molecular biology at UTMB, this way of measuring the immune response is more accurate than traditional methods.

The sensitivity and the dynamics of the assay, because of the luciferase, can really allow us to discern any small changes that the conventional way would not, said Xie. Its much more sensitive, much more accurate, when you test antiviral compounds.

The compounds to which Xie is referring are potential therapies, including antiviral drugs already on the market for non-COVID-19 viral infections.

The researchers recently tested every antiviral drug approved by the FDA for human use to see if any were effective against SARS-CoV-2.

These assays allow us to very rapidly look at each in a very sensitive way very accurately, Shi said. Thats really allowed us to decide whether there is a potential so-called repurposing of these drugs for COVID-19 treatment, including remdesivir, chloroquine and others.

The virologists also have created a system for manipulating and studying SARS-CoV-2 itself, paving the way for a deeper understanding of what happens when the virus enters the human body.

Because of this system we created, we can study and understand the virus in ways that others cannot, Baker said. We have the ability to go in and make changes in the virus and see what those changes affect in the different cells that its infecting. So, not only have we developed these assays to look at drugsto look at antibody responsesbut we also are probing the virus itself and looking at how it interacts with the immune system.

Even more, the team is studying the virus genome to analyze how it has evolved and what that means for human healthincluding how it affects the body and how it transmits among different populationsusing techniques they developed for studying Zika and its connection to microcephaly, a neurological condition in which an infants head is significantly smaller than other infants of the same gender and age.

When we manipulate the viruses, it allows us to address a lot of important questions, such as how the virus is adapting and changing over time, Shi said. For example, SARS-CoV-2 now has been spreading in humans for six monthshas the virus changed? Do these changes affect viral transmission and disease severity? Scientists around the world have been chasing the virus to answer those exact questions.

Shi noted that his lab is sharing innovations with scientists worldwide to help advance public health efforts as quickly as possible.

He hopes his research will light the way.

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Fireflies help kindle new tests and treatments for COVID-19 - TMC News - Texas Medical Center News

Meet Dr Sarah Gilbert, one of the scientists leading the race to find a Covid-19 vaccine – The Indian Express

Written by Dipanita Nath, Edited by Explained Desk | Pune | Updated: July 25, 2020 4:42:06 pm Professor Sarah Gilbert, who is leading development of a coronavirus vaccine at Oxford University, in Oxford, April 24, 2020. (Mary Turner/The New York Times)

Earlier this week, there was positive news on the Oxford vaccine candidate, one of a clutch of frontrunner candidates to protect the world from the SARS-CoV-2 virus that had, until Friday (July 24) morning, infected nearly 15.5 million people and killed over 630,000 worldwide.

Leading its development is a British scientist who plays the oboe, cycles to work, and is the mother of triplets. Dr Sarah Gilbert was famous in the scientific community as a brilliant vaccinologist; with the success in early trials, she and ChAdOx1 nCoV-19, the vaccine candidate her team is working on has been spotlighted as never before.

Gilbert and co-authors published the results of the early trials in the medical journal, The Lancet, on July 20, titled Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. They wrote: ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. Which means that the vaccine candidate had induced an immune response (which is what vaccines are supposed to do), and was safe for people.

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What is Dr Gilberts work in the field of vaccine development?

Dr Gilbert is one of the leading vaccinologists in the world. She is professor of vaccinology at Oxford Universitys Jenner Institute, a prestigious vaccine research centre, and one of the two founders of its spin-out company, Vaccitech, which develops immunotherapy products to treat and prevent infectious disease and cancer.

For more than 15 years, Dr Gilbert has been making and testing vaccines that trigger T cells a type of white blood cells to respond to antigens from malaria, influenza, and tuberculosis, among others.

Her work also includes developing vaccines for influenza and emerging diseases such as Lassa, Nipah, CCHF, and Middle East Respiratory Syndrome (MERS). MERS, which appeared in 2014, too, is caused by a coronavirus. A vaccine against MERS has been tested in clinical trials in the UK, and is now in trials in Saudi Arabia, where the virus is endemic, says Gilberts page on the Jenner Institute website.

The vaccine for MERS involved using the adenovirus (which causes common colds) from a chimpanzee embedded with the genetic material of the MERS virus. For the Covid-19 vaccine, the Oxford scientists used the adenovirus of a chimpanzee embedded with the genetic material from the spike protein, which the coronavirus uses to pierce the cell. In tests till now, bodies of participants have responded as if they were infected with the coronavirus.

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What is known about the acclaimed scientists life away from her work?

Dr Gilbert has not given many interviews since the publication of the results of the early phase trials. Earlier profiles of the scientist in the UK media have said that as a child in Northamptonshires Kettering High School for Girls, she was quiet, polite, and studious, getting a lot of As in studies.

Gilbert belongs to a family of musicians, and her mother, Hazel, was part of the towns operatic society. By the age of 17, however, Gilbert was sure that she wanted to be a medical researcher. After obtaining a degree in biology at the University of East Anglia and a PhD in biochemistry from the University of Hull, Dr Gilbert worked at a number of biotechnology companies, among them Delta, where she learnt about making medicines.

Profiles on Prof Gilbert have noted that she became a vaccine specialist rather by accident. In 1994, when she entered Oxford University to join Professor Adrian Hills lab in a senior postdoc position, it was to work on human genetics. That highlighted the role of a particular type of immune response in protection against malaria, and so the next thing to move on to was to make a vaccine that would work through that type of immune response and thats how I got into vaccines, she told UKs The Telegraph newspaper in an interview.

By 2007, Dr Gilbert, who had become a reader at Oxford University three years previously, had won a project grant from the Wellcome Trust, and had begun work on an influenza vaccine. She has developed two vaccines for the disease so far, and has said that her ultimate aim is to be able to develop her team of scientists to be the leaders in vaccine research in the world.

Many people are fascinated with Dr Gilberts success in balancing the extra demands that women with a career in science face.

According to UNESCO, women make up less than 30 per cent of the worlds researchers. In science, technology, engineering and mathematics, women also publish less, are paid less for their research and do not progress as far as men in their careers.

On the website of the Nuffeld Department of Medicine (of which Jenner Institute, where she works, is a part), Dr Gilbert has been quoted as saying: Work life balance is very difficult, and impossible to manage unless you have good support. Because I had triplets in 1998, nursery fees would have cost more than my entire income as a post-doctoral scientist, so my partner has had to sacrifice his own career in order to look after our children.

She described how 18 weeks of paid maternity leave with three premature babies to care for and work to be completed, was tough: If there is a three-year grant and a woman wants a year-long maternity leave, it can disrupt the progress of the project. The situation becomes worse if more than one person is away simultaneously.

Dr Gilberts advice to women: One of the good things about being a scientist is that the hours are not fixed, so there is a fair amount of flexibility for working mothers. Having said that, there are also times when things (such as overseas conferences and important meetings) are fixed and you have to make sacrifices. It is exceptionally hard work. Its important to plan ahead, and make sure you have people who are willing to cover for you at home while you work. That might be your partner or relatives, or you may be able to buy in help.

Her own children seem to have survived unscathed, but none of them wants to be scientists, she said.

Dr Gilbert is cautiously hopeful. In an interview to the BBC, she said, Nobody can be absolutely sure that it is possible. Thats why we have to do trials. I think the prospects are very good but it is not completely certain.

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Meet Dr Sarah Gilbert, one of the scientists leading the race to find a Covid-19 vaccine - The Indian Express

Black American’s genes reflect the hardships and realities of slavery – NBC News

The graphic shows the three main research findings by 23andMe.23andMe

The genes of 50,000 descendants of slaves reveal the effects of the global slave trade generations later, according to a study published Thursday in the American Journal of Human Genetics. Researchers analyzed data provided by thousands of 23andMe customers who agreed to share their genetic information to better understand the impact of forced migration on the genealogy of the descendants of enslaved Africans in the Americas.

They found that enslaved people who were brought from one African region to a particular region in the Americas generally ended up sharing a genetic connection to that African region generations later, said Steven Micheletti, a population geneticist with 23andMe and the first author of the study.

But, in some cases the results did not line up with the historical records. For instance, while African Americans, based on migration documents, should show genetic roots closely linked to current day Angola and the Democratic Republic of Congo, many actually show closer genetic links to Nigeria.

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High percentages of Nigerian ancestry in African Americans in the U.S. may be linked to the number of slaves who were transferred from the British Caribbean to the United States. This was backed up by historians who cited a database on the intra-American slave trade, which made it clear that slaves had been brought from the Caribbean to the U.S., said Joanna Mountain, 23andMes senior director of research. When you look back at the pattern of slaves brought to the Caribbean, especially the British Caribbean, you see that that was often from Nigeria.

Dr. Bernard Powers, historian and director of the Center for the Study of Slavery in Charleston, part of the College of Charleston in South Carolina, suggests that the origin of slaves shipped from the Caribbean to the U.S might be difficult to track. But he said the genetic discrepancy may be the result of migrations by people from what is now southeastern Nigeria to parts of Angola and Congo who were later captured and sent to America.

There could have been internal developments within the African continent, which shaped the exportation of slaves, Powers said. Each one of these regions has its own political and economic, as well as climate history, and the variations could contribute to the exportation of people on the coast.

Powers and the researchers agree that once slaves from Senegal and Gambia, an area also known as Senegambia, arrived in the U.S, they suffered high mortality rates on rice plantations where malaria and gruesome work conditions were common. Rice was really the most labor intensive crop produced in Colonial America, for sure, Powers said. It would have been the mainlands approximation to sugar cultivation in the Caribbean.

Mountain suggested that the high mortality rates may have contributed to reduced genetic representation of enslaved people from Senegambia, Angola, and the Democratic Republic of Congo in African Americans.

Despite differences in the practice of slavery among countries and colonies across the Americas, researchers also found an overarching sex-bias that appeared throughout the continents.

Sex-biases is basically the ratio of African women that were reproducing to African men, said Micheletti. African women were reproducing way more than African men were. That's indicative of rape and exploitation that has been documented in diaries and other historical literature.

The researchers recognize that their data lacks representation of global populations due to 23andMes mostly U.S. customer base. Yet, they say looking at genetics through the lens of historical data could bring awareness to new truths about ancestry.

We don't want these historical details to get swept under the rug, Micheletti said. We really want them to be discussed today, and adding the genetic confirmation on to those details could be a powerful tool.CORRECTION (July 23, 2020, 6 p.m. ET): A previous version of this article misstated in one reference where in Africa researchers say slaves to the U.S. came from. It was Senegal and Gambia, an area they've labeled Senegambia, not Angola and the Republic of Congo. (The researchers made the correction after publication.

Isoke Samuel is a news fellow with NBC News Digital.

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Black American's genes reflect the hardships and realities of slavery - NBC News

Human Genetics Market Research, Key Players, Industry Overview, Supply and Consumption Demand Analysis by 2026 – Owned

Aimed at offering report readers with updated information as well as market relevant cues to leverage uninhibited growth in the Human Genetics market, this intricately researched, designed, and articulated real-time reference of the Human Genetics market is a culmination of in-depth research mettle and best in class primary and secondary research initiatives that collectively influence a favorable growth trajectory in the Human Genetics market. The report is a ready-to-refer market specific representation that is designed to equip report readers with market specific information attributed to multi-dimensional facets and features that tend to have tangible effect on the growth prospects in the Human Genetics market.

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The report highlights massively the core growth propellants such as market driving factors, prevailing challenges and the like that tend to have a negative growth impact on the global Human Genetics market. Further, to encourage readers in a decisive, transparent and meticulous declassification of the growth factors, this section of the report also sheds substantial light upon potential opportunity profile as well as a highly effective barrier analysis that together encourage sturdy growth in the global Human Genetics market.

Major companies of this report:

QIAGENAgilent TechnologiesThermo Fisher ScientificIlluminaPromegaLabCorpGE

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CytogeneticsPrenatal GeneticsMolecular GeneticsSymptom GeneticsMarket

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Triplet Therapeutics Selects Clinical Candidate for Novel Treatment of Repeat Expansion Disorders – Business Wire

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Triplet Therapeutics, Inc., a biotechnology company leveraging insights from the human genetics of repeat expansion disorders (REDs), announced today the selection of TTX-3360 as the first clinical candidate developed from Triplets proprietary thRED Engine. TTX-3360, an antisense oligonucleotide, is the first therapeutic candidate with the potential to modify the course of REDs, including Huntingtons disease, by targeting the DNA Damage Response (DDR) pathway.

The development of TTX-3360 is an important step towards our goal of treating REDs at the genetic level by targeting the primary driver of disease, said Nessan Bermingham, Ph.D., Triplets chief executive officer, president, and co-founder. Based on our data as well as an extensive body of evidence from patient genetics our target in the DDR pathway has the potential for significant therapeutic impact across many of these devastating diseases.

REDs are a group of more than 50 known genetic diseases associated with DNA nucleotide repeats, many of which have been shown to lengthen, or expand, in cells over a patients lifetime. A significant body of evidence, including patient genome-wide association studies across multiple indications, supports the role of the DDR pathway as the primary driver of repeat expansion and subsequent disease onset and progression.

Preclinical data, including findings presented this year by Triplet at the annual meetings of CHDI and the American Society of Gene and Cell Therapy, indicate that ~50% knockdown of a single target in the DDR pathway can slow or stop the expansion of DNA repeats in vitro in human patient-derived cell lines and in vivo in Huntingtons disease model mice.

Recent experiments by Triplet demonstrated that a single dose of TTX-3360 induced significant knockdown of the target gene mRNA at 29 days in the cortex (>75%) and caudate (>45%) in non-human primates. No adverse events were observed, and the treatment was well-tolerated, at the therapeutic dose.

Triplet plans to initiate IND-enabling studies in the second half of 2020 and to file an IND in the second half of 2021, with an initial focus on Huntingtons disease. TTX-3360 may also be expanded into other central nervous system indications including spinocerebellar ataxias, fragile X syndrome, and familial amyotrophic lateral sclerosis (ALS). To support its clinical development, Triplet recently launched an international natural history study, SHIELD HD, to assess clinical outcomes and biomarkers that will inform future clinical trials.

Thousands of patients with REDs currently have no disease-modifying therapeutic options, said Irina Antonijevic, M.D., Ph.D., Triplets chief medical officer. "We are excited to be moving quickly toward a first-in-human trial in Huntingtons disease and ultimately toward therapies with the potential to slow or prevent these devastating disorders.

About Huntingtons disease

Huntingtons disease is a genetic disorder linked to a mutation in the HTT gene characterized by an increase in the number of CAG repeats within the gene. The presence of these repeats, beyond a certain threshold, wreaks havoc on brain function, affecting mood, cognition and motor skills, ultimately leading to death. Thanks to the contributions of thousands of patients whose participation in genetic research has built a fundamentally new understanding of the cause of REDs it is now known that the number of repeat sequences expands over time in patients, increasing the toxic impact on cells, particularly neurons. The DDR pathway plays a central role in driving this process.

About Triplet Therapeutics

Triplet Therapeutics is a biotechnology company developing transformational treatments for patients with repeat expansion disorders (REDs) a group of more than 50 known genetic diseases including Huntingtons disease, myotonic dystrophy, spinocerebellar ataxias, fragile X syndrome, and familial amyotrophic lateral sclerosis (ALS) leveraging insights from patient genetics. Triplet designs and develops potential therapeutics for REDs using its proprietary thRED Engine, which enables the Company to develop a single oligonucleotide targeting the DNA Damage Response (DDR) pathway to potentially treat multiple REDs.

Triplet is backed by investments from Atlas Venture, MPM Capital and Pfizer Ventures, along with Invus, Partners Innovation Fund and Alexandria Venture Investments. Triplet is headquartered in Cambridge, Mass. For more information, please visit https://www.triplettx.com/

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Triplet Therapeutics Selects Clinical Candidate for Novel Treatment of Repeat Expansion Disorders - Business Wire

PacBio’s Focus on Human Genomics And Read Length Sweet Spot – Bio-IT World

By Allison Proffitt

July 21, 2020 |It seems like a very long time ago, now, that Illumina and Pacific Biosciences dissolved their merger agreement, but in fact their announcement is just about six months old. Since then, PacBio has been busy reestablishing itself as an independent business and looking ahead, their sights set on the human genome sequencing market.

The dissolution of the Illumina mergercalled off due to the lengthy regulatory approval process and continued uncertaintydid require some back-pedaling. We were actively moving as much as we could without the full regulatory review having completed, Luke Hickey, Senior Director of Strategic Marketing, told Bio-IT World. But Hickey is optimistic about PacBios future.

There was a fairly large breakup fee that ended up giving us significant operating capital, Hickey said of the $98 million termination fee. We have a healthy balance sheet and wereif anythingmore energized to continue as an independent company within the long read space.

As for competitive exposure, Aaron Wenger, Principal Scientist at PacBio, is not worried.

I know that there was some sharing of information, but PacBio has been developing SMRT sequencing for, I think, 20 years, Wenger said. I think there are ways to protect the technology through patents that Illumina can't legally copy, and then also I think many trade secrets that they did not have access to. An added strength, Wenger noted: the many people who could actually execute that on the day to day basis here are still employed at PacBio.

Hickey agreed. We feel like were in an incredibly strong position with the patent portfolio andto Aarons pointhow many years its taken to develop a robust and reliable system for doing the sequencing.

The PacBio sequencing system announced an overhaul itself in 2019. About a year ago, the company launched its Sequel II platform. PacBio shipped 104 Sequel II platforms to customers between June and December 2019, Hickey said, highlighting a healthy mix of existing and new customers. While PacBios historical customers may have focused on microbial or plant and animal sequencing, We have seen just great adoption from the human biomedical market, he emphasized. He name-dropped a few groups to adopt the new platform: the NIHs All of Us program, Mercy Childrens Hospital in Kansas City, Ira Halls group at Washington University in St. Louis, and Evan Eichler at the University of Washington.

The Sequel II system takes advantage of a new read typeHiFi readsthat the company announced in January 2019. The corresponding paper was published in Nature Biotechnologyin August 2019; Wenger is first author (DOI: 10.1038/s41587-019-0217-9). The team optimized circular consensus sequencing (CCS) to improve the accuracy of single-molecule real-time (SMRT) sequencing and generate highly accurate (99.8%) long high-fidelity (HiFi) reads with an average length of 13.5kilobases (kb).

What we were able to do, was significantly increase the efficiency of being able to get multiple observations of the DNA molecule, Wenger explained, through repetitive or circular sequencing of the same DNA. That first time through you detect with 87% accuracy. Then you go around the turn and go back in the other direction and now you get another read thats 87% accurate. But its an independent read from the first one. Now you have two things, each of which are 87% accurate, but you make different mistakes in the two times through. By making multiple observations in series of the same physical DNA molecule, you can generatein softwarea consensus of those passes, he said. If you do 5 passes, you can get 99% accuracy; if you get 8 passes, you get 99.9% accuracy.

The result is highly accurate reads that are opening up new applications.

Our CCS method matches or exceeds the ability of short-read sequencing to detect small variants and structural variants, Wenger and his co-authors wrote in August 2019 paper. De novogenome assembly using CCS reads alone produced a contiguous and accurate genome with a contig N50 of >15megabases (Mb) and concordance of 99.997%, substantially outperforming assembly with less-accurate long reads.

The Sequel II platform enabled researchers to generate the new read type at greater scales than before. By April 2019, at least five early adopter institutions were using Sequel II platforms, and Luke Tallon from the University of Maryland Institute for Genome Services reported seeing, comparable data quality with yields 8-9 times higher than that of the Sequel.

The new platform and read types have been included in several publications including a paper from the PacBio team with scientists from the University of Washington describing improved assembly and variant detection of a haploid human genome published in the Annals of Human Genetics(DOI: 10.1111/ahg.12364). Two additional papers are in review and published on bioRxiv.

Already there have been some interesting trends emerging, Wenger said: some things you would have predicted, and some things we didnt.

Sequencing has labored under a general wisdom, Wenger said, that short, very accurate reads are critical to calling small variants like single nucleotide variants, while do novoassembly required long reads, even with less accuracy. But the HiFi reads, Wenger says, have struck a middle ground. They are accurate and longer (though not as long as longest PacBio reads): about 15,000-20,000 base pairs at greater than 99% accurate.

The question is, how does do these HiFi reads perform compared to either the short or long reads we are used to? Whats interesting is actually seeing thatat least for human genomesthese highly accurate, pretty long reads just significantly outperform even reads that are 100,000 or 150,000 bases long, Wenger says.

A HiFi read that is 20,000 base pairs long and 99% accurate is superior to a 60,000 base pair read that is 85% accurate, Wenger argues. When you call something in the genome a repeat, theyre never 100% identical, he said. If two things are 98% identical in the genome, but your reads are 99% accurate, then you can tell those two things apart. This accuracy lets you resolve more repeats than having long reads.

Wenger says this balance between read length and accuracy is not only scientifically interesting, but also somewhat surprising. At this current point [with the Sequel II], what the platform can deliver is likely enough to completely assemble human genomes from telomere to telomere, he says.

New Applications

There is a group working on that. The Telomere to Telomere Consortiumis an open, community-based effort headed by Adam Phillippy of NIH/NHGRI and Karen Miga of UC Santa Cruz. Their goal is to sequence human chromosomes from end to endincluding tricky centromeresfilling hundreds of gaps across the genome including segmental duplications, ribosomal rRNA gene arrays, and satellite arrays.

We aim to finish these remaining regions and generate the first truly complete assembly of a human genome, the group writes on their website. The ultimate goal of this effort is to drive technology to dramatically increase the throughput of complete, high quality telomere-to-telomere assemblies from diploid human genomes.

At AGBT in 2019 (Feb 27-March 2), Phillippy presented the sequence of the full human X chromosome which was assembled, then iteratively polished with a combination of technologies from Oxford Nanopore, PacBio (both the continuous long reads and the HiFi reads), 10x Genomics/Illumina, and Bionano Genomics. Since then, Wenger says, HiFi has been used to sequence through more centromeres. Now with the HiFi reads, a number of groups have been able to assemble centromeres. Now, I think, theyve assembled nearly half the human centromeres using 15,000 to 20,000 base pairs and 99% accuracy rate, he said. (The sequenced X chromosome was published July 14 in Nature, DOI: 10.1038/s41586-020-2547-7.)

The Human Pangenome Reference Sequence Project is another project making use of the combination of long reads plus accuracy, Hickey added. That project includes researchers from the University of Washington, Washington University and the University of California, Santa Cruz. The two sequencing centersUniversity of Washington and Washington Universityare using the PacBio HiFi reads as the primary sequencing technology for assembly, Hickey said. The group will also use Oxford Nanopore for scaffolding work. The group has done 30 human reference genomes this year, Wenger addeda huge increase from output in the past.

Sweet Spot

The Sequel II and HiFi reads mark a shift in PacBios technical focus moving forward. Wenger says that 20,000 bases is, likely sufficient for anything youd want to do in a human genome, so pushing for longer read lengths isnt a priority. There are still a few centromeres that have to be finished, so maybe youll need 30,000 for those. But Im kind of skeptical. I think that 20,000 is going to be plenty and that its just continued algorithmic improvements that will take it the rest of the way, he said.

He also pointed out a practical reason that 20,000 base pairs is an ideal read length. We found that the 20,000 base-pair-range is the comfortable range where people can collect samples, consistently process them, and generate good libraries at that read length. When you try to push to more extreme read lengths, there become a lot more limitations on sample collection and libraries fail a lot more. Thats not a problem with the sequencing technology, thats a problem with the upstream DNA handling.

Hickey agreed. The next step for us is not necessarily to drive up read lengths, because we think that is sufficient, but to drive down the cost. Thats our roadmap for 2020 We are trying to get to one human genome, on one SMRT cell, in one day. For just over $1,000 in consumable costs, Hickey points out, and could give you, all of the answers you want.

Hickey sees clinical utility in the platforms future. The NIH-funded research has an eye toward eventual clinical applications and he mentions a HudsonAlpha group exploring the Sequel II for diagnostics.

As those studies get published, that will really set us up for maybe more of push into the clinical market for using the whole genome sequencing with HiFi in a more routine way, Hickey said. But certainly for the next few years, well be in this basic human genetics research, and then all of this translational, clinical, exploratory research realm to demonstrate utility.

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Staten Biotechnology, in collaboration with Novo Nordisk, starts dosing of anti-apoC3 antibody SST-5058 in First-in-Human Trial | Antibodies | News…

DetailsCategory: AntibodiesPublished on Tuesday, 21 July 2020 11:10Hits: 179

Clinical trajectory initiated towards development of novel treatment for dyslipidaemia

NIJMEGEN, The Netherlands I July 21, 2020 I Staten Biotechnology B.V. announced today the initiation of dosing of the Companys lead asset, STT-5058, in a First-in-Human clinical study.

STT-5058 is a monoclonal antibody that targets the lipoprotein ApoC3 and is being developed in collaboration with Novo Nordisk. Staten Biotechnology and Novo Nordisk entered a collaboration and exclusive option agreement in December 2018 to develop novel therapeutics for the treatment of dyslipidaemia. Novo Nordisk is providing funding and support to Staten for the development of STT-5058 in this indication.

Hilde Steineger, CEO of Staten Biotechnology, said: Staten Biotechnology, with great support from Novo Nordisk, has been able to rapidly progress from research to product manufacturing to a clinical trial for our lead drug candidate. We are very excited to dose the first healthy volunteer.

Professor John Kastelein, Chief Medical Officer of Staten Biotechnology, added: The commencement of the FIH trial is an important milestone for the Company. We believe STT-5058, based on its favourable safety profile and novel mechanism targeting ApoC3, which is supported by human genetics, has the potential to address an unmet medical need in patients with mixed dyslipidaemia and high cardiovascular risk.

About Staten Staten Biotechnology B.V. aims to develop novel and innovative strategies for the treatment of dyslipidaemia, with a focus on hypertriglyceridemia treatment. BioGeneration Ventures (BGV) provided the companys seed financing in 2014 and Forbion led the Series A round, as the sole new investor. Staten is a prime example of Forbions and BGVs company building activities, growing great scientific ideas into promising companies. For further information: http://www.statenbiotech.com

About STT-5058 STT-5058 is a humanized, monoclonal antibody targeting novel and unique epitopes on apoC3. This recycling antibody with extended half-life has the potential to lower triglyceride levels and increase clearance of ApoC3-containing atherogenic particles. Multiple studies have identified ApoC3 levels to be inversely associated with a favourable lipid profile and insulin resistance, both key components in managing residual cardiovascular risk. This antibody was licensed from Statens research collaboration partner argenx and is developed in collaboration with Novo Nordisk.

About ApoC3 ApoC3 is a small apolipoprotein that inhibits the uptake of lipoprotein particles by the liver and inhibits the activity of lipoprotein lipase leading to high levels of lipoproteins and triglycerides. It is secreted from the liver and small intestine and circulates on both triglyceride-rich lipoproteins such as very-low-density-lipoproteins (VLDL), chylomicrons in addition to high-density lipoproteins. Population groups with loss-of-function mutations in apoC3 have reduced incidence of vascular and heart diseases. High levels of apoC3 correlates with higher amounts of triglycerides and increased incidence of vascular and heart disease. This supports the potential of the anti-apoC3 antibody to act as key molecule in dyslipidemia management.

SOURCE: Staten Biotechnology

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Staten Biotechnology, in collaboration with Novo Nordisk, starts dosing of anti-apoC3 antibody SST-5058 in First-in-Human Trial | Antibodies | News...

FDA Action Alert: Jazz, ANI and Ultragenyx – BioSpace

Wrapping up the month of July, there are three PDUFA dates on the U.S. Food and Drug Administration (FDA) calendar, although one of the drugs has already been approved and another company is in the process of refiling their application. Heres a look.

Jazz Pharmaceuticals Drug for Cataplexy

Jazz Pharmaceuticals has a target action date of July 21 for its New Drug Application (NDA) for JZP-258 for cataplexy or excessive daytime sleepiness (EDS) in patients seven years of age and older with narcolepsy. The drug is a novel oxybate product with a unique composition of cations resulting in 92% less sodium than Jazzs Xyrem (sodium oxybate).

At this time, Xyrem is the only product approved to treat both cataplexya sudden loss of muscle tone with retained consciousnessand EDS in patients with narcolepsy ages seven years and older.

We developed JZP-258 to be a safer and long-term treatment option for patients, said Robert Iannone, executive vice president, research and development of Jazz, back in March when the FDA accepted the NDA application. JZP-258 represents between 1,000 and 1,500 milligrams daily reduction of sodium for patients currently treated with Xyrem, depending on the dose. Given the broad scientific consensus that reducing daily sodium consumption is associated with clinically meaningful reductions in blood pressure and cardiovascular disease risk, we believe that JZP-258 has the potential to be an important treatment option for patients living with the life-long condition of narcolepsy. Narcolepsy patients are known to be at increased risk of comorbidities, including obesity, hypertension, diabetes and dyslipidemia.

ANI Pharmaceuticals Purified Cortrophin Gel Prior Approval Supplement

ANI Pharmaceuticals had a target action date of July 23, 2020, for its supplemental new drug application (sNDA) for Purified Cortrophin Gel (Repository Corticotropin Injection USP). In an announcement in March, when it submitted the sNDA, the company noted the current annual market for the drug is about $950 million and there is only one competitor.

Cortrophin Gel was originally approved by the FDA in 1954 and halted use in the 1980s. The drug has more than 54 indications in its previously approved label, including acute exacerbations of multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and ulcerative colitis. The company acquired the NDA from Merck in January of 2016 and spent more than four years and over $100 million to re-establish and validate the commercial corticotropin active pharmaceutical ingredient and the drugs manufacturing processes. This included rebuilding a U.S.-based supply chain.

On April 28, the FDA issued a Refusal to File (RTF) letter regarding the sNDA. The FDA said on preliminary review, certain portions of the Chemistry, Manufacturing and Controls section were not sufficiently complete to permit a substantive review. On June 1, ANI provided an update and indicated it plans to refile the sNDA when it completes the review process.

Ultragenyx Pharmaceuticals UX007 for Long-chain Fatty Acid Oxidation Disorders

Ultragenyx Pharmaceuticals has a target action date of July 31 for UX-007 for long-chain fatty acid oxidation disorders (LC-FAOD). On June 30, the FDA approved UX007 (triheptanoin) under the trade name Dojolvi.

LC-FAOD are a group of rare, lifelong and life-threatening genetic disorders. In them, the body cannot convert long-chain fatty acids into energy. Dojolvi is a highly purified, synthetic, 7-carbon fatty acid triglyceride designed to provide medium-chain, odd-carbon fatty acids as an energy source and metabolite replacement for LC-FAOD patients. When people are born in the U.S. and certain European countries, LC-FAOD is included in newborn screening panels because of the risk for serious health issues, including early death. The current treatments include avoiding fasting, low-fat/high-carbohydrates diets, carnitine and even-carbon medium-chain triglyceride (MCT) oil, a medical food product. These diseases affect about 2,000 to 3,5000 children and adults in the U.S.

FDA approval of Dojolvi for the treatment of long-chain fatty acid oxidation disorders is a huge milestone for patients and their families, as it is the first such medication, said Jerry Vockley, Professor of Human Genetics and chief of Medical Genetics at Childrens Hospital of Pittsburgh of UPMC. While we have been able to identify these disorders at birth for many years, treatment options have been limited. Dojolvi brings hope as a new tool now available to clinicians taking care of these patients.

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FDA Action Alert: Jazz, ANI and Ultragenyx - BioSpace

Humanized Mouse Model Market Key Players are Aggressively Investing on Research and Development – BioSpace

TMR Research speaks on the core issues and characteristics of the global humanized mouse model market, along with its nuances and opportunities of growth over the coming years, in Humanized Mouse Model Market Global Industry Analysis, Size, Share, Trends, Analysis, Growth, and Forecast 2017 2025.

The leading factor augmenting the growth rate of the global humanized mouse model market at the moment is the high demand posed by the pharmaceutical industry. The prevalence of diseases has been on the rise over the years and the healthcare and pharmaceutical industry are hard pressed to find optimal solutions for the incoming waves of both new and old diseases. This is creating a very high demand for humanized mouse models, especially in the pharma business, where research benefits massively through the use of mice that are integrated with human DNA, microbiomes, tumors, or tissue. The mice also hold a high value in the fields of genetics and drug development.

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National governments are also playing an important role in the overall development of the global humanized mouse model market through increasing incentives and investment initiatives. The growing number of incentives and grants received by the leading players in the market is expected to propel the global humanized mouse model market over the coming years.

The genetic models segment is expected to show the greater demand volume in the global humanized mouse model market over the coming years, above cell-based humanized mouse models. This demand is speculated to rise due to the increasing scope of applications that genetic model mice will hold.

Geographically speaking, the global humanized mouse model market can be segmented on the basis of the key regions involved. North America has been leading the market over the recent past, thanks to an advanced pharmaceutical infrastructure where investments for research and development are very high. It is likely for North America to remain in the lead over the coming years. Meanwhile, the booming healthcare and pharmaceutical infrastructure across Asia Pacific is expected to provide a massive surge to the global humanized mouse model market in the immediate future.

The leading players in the global humanized mouse model market, at the moment, include Horizon Discovery Group PLC, genOway S.A., Axenis S.A.S, ingenious targeting laboratory, HuMurine Technologies, Inc., Harbour Antibodies BV, and The Jackson Laboratory. The competitive landscape of the market is such that the leading entities are extremely focused on investing more in research and development. At the same time, they are interested in improving their professional profile through mergers and acquisitions.

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The widespread drive for humanized mouse models has stemmed from the substantial need for robust pre-clinical animal models for the study of a spectrum of human diseases. These animal models are proving to be promising in closely reflecting human biological systems. The rising clinical use of humanized mice in expanding our understanding of cancer therapies, regenerative medicine, allergies, and immunity-related diseases is propelling the growth of the market.

To shed in-depth light on such trends and factors influencing the growth trajectory of the market, TMR Research has published a new report, titled, Humanized Mouse Model Market Global Industry Analysis, Size, Share, Trends, Analysis, Growth, and Forecast 20172025.

The attractive demand for humanized mice models for pre-clinical tools for biomedical research to discover more efficacious drugs is boosting the market. The rise in strategic mergers and acquisitions entered by pharmaceutical companies in various parts of the world to boost drug discovery activities is fortifying the demand for these cutting-edge platforms. The sizeable funds and grants committed by governments in several countries for research and development activities related to humanized model is providing a robust catalyst to the demand.

The growth of the humanized mouse models market is expected to reflect well from the rising efforts by pharmaceutical and biotech companies in personalized medicines. The growing adoption of mouse models with humanized immune systems to act as in vivo platform for assessing the efficacy of new drugs is also propelling the markets growth. They prove to be useful in-vivo models for graft rejection research. Furthermore, the notably rising demand for cell-based humanized mouse models in genetic studies world over is accentuating the market.

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Some of the prominent players holding a substantial stake in the global humanized mouse models market are The Jackson Laboratory, Harbour Antibodies BV, HuMurine Technologies, Inc., Ingenious Targeting Laboratory, Axenis S.A.S, GenOway S.A., and Horizon Discovery Group PLC.

About TMR Research

TMR Research is a premier provider of customized market research and consulting services to business entities keen on succeeding in todays supercharged economic climate. Armed with an experienced, dedicated, and dynamic team of analysts, we are redefining the way our clients conduct business by providing them with authoritative and trusted research studies in tune with the latest methodologies and market trends.

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Humanized Mouse Model Market Key Players are Aggressively Investing on Research and Development - BioSpace

Coronavirus is not mutating to be weaker over time, genetics show – Business Insider – Business Insider

People wear face masks as they attend the live broadcast of Pope Francis' Sunday Angelus prayer at Saint Peter's Square in Vatican City, March 8, 2020. Antonio Masiello/Getty Images

Experts continue to throw out conflicting ideas about whether the coronavirus has changed. Some Italian doctors say it's gotten weaker over time. A group of researchers has suggested the opposite: that a mutated version of the virus became dominant worldwide because it's more transmissible than the original.

All viruses, including the coronavirus, change over time by accumulating mutations as they replicate. But according to Emma Hodcroft, a geneticist at the Nextstrain project, there's still no evidence this virus changed in any significant way not to become less deadly, and not to be more contagious.

The Nextstrain project has been tracking changes in the coronavirus for months. So far, Hodcroft's team has collected and sequenced the genome of thousands of virus samples collected around the world since December 2019.

Geneticists differentiate these samples into five clades the term for groups of virus samples that have descended from a common ancestor characterized by mutations that have accumulated over time in one or more of a dozen genes.

But none of those mutations have meaningfully changed how lethal or infectious the coronavirus is, Hodcroft said.

It's easy to think that humanity's attempts to control the coronavirus's spread via social distancing, mask wearing, and lockdowns may have applied evolutionary pressure on the virus. Given impediments to its spread, this line of logic suggests, perhaps the virus might evolve to improve how it passes between people.

But according to Hodcroft, the virus has no significant impetus to change right now.

"The virus is very successful at what it's doing most people who get infected don't die. They pass along the virus to a new host and recover," Hodcroft said. "It's current strategy has helped it cover the whole world in months."

People wearing masks wait on a crowded subway platform on May 30, 2020, in New York City. Alexi Rosenfeld/Getty Images

If the original strain of the coronavirus killed its host within a few days, then perhaps it might have mutated over time to not kill as quickly, she added that would give it more opportunities to jump to new hosts. But on average, people die of COVID-19 18 to 19 days after symptoms start, according to a study from Wuhan, China.

Alternatively, if social distancing were having an effect, Hodcroft said, the coronavirus might mutate to become more infectious "to overcome barriers we put in its way."

Research has in fact shown that a mutated coronavirus strain became dominant worldwide one that appears to be more transmissible between human cells than the original virus. But Hodcroft said the strain might simply have gotten lucky, since it ended up being the version that spread to countries in Europe and North America. Many of those countries did not enact lockdowns for weeks after their first cases appeared, which allowed that version of the virus to proliferate.

Plus, scientists still aren't sure whether observations at the cellular level apply to real people.

"We don't know how things we see in a lab scale up to a size of a full human. Transmissibility in cells and people are completely different ballgames," Hodcroft said.

An artists's rendering of the coronavirus. Corona Borealis Studio/Shutterstock

She added that such mutations, though possible, "happen over decades or centuries."

In a June op-ed, 10 Italian doctors suggested that the coronavirus was weakening and had changed to be less lethal.

The "virus from the clinical point of view no longer exists" in Italy, they wrote, citing a marked reduction in symptomatic coronavirus cases and hospitalizations. The op-ed also noted that viral loads how much of the virus is present in swabs from many Italian patients were so negligible that patients were not even contagious.

"The concentration of viral RNA on the swab is so small that it does not infect anything," Giuseppe Remuzzi, one of the op-ed co-authors, told Politico last week.

A hospital employee wearing protective gear shows a cotton swab for taking a coronavirus sample. Miguel Medina/AFP via Getty

But Hodcroft said"there isn't any validity to those claims."

In fact, she added, it's "misleading for Italian doctors to say this when they're looking at only Italian patients."

Michael Ryan, the executive director of WHO's Health Emergencies Program, similarly warned in June: "We need to be exceptionally careful not to create a sense that all of sudden the virus, by its own volition, has now decided to be less pathogenic. This is still a killer virus."

Nurses transport a COVID-19 patient in a biological containment stretcher in the Da Procida Hospital in Salerno, Italy, in April. Ivan Romano/Getty Images

The more likely explanation for the trend the Italian doctors have observed, Hodcroft said, is that in March, Italy's healthcare system was strained, so most patients admitted to the hospital had very severe cases. At that time, about 6,500 new cases were being reported per day in Italy. But by the end of May, the number had dropped to about 300. That may have enabled more Italians with milder cases to get care, which could explain the lower viral loads in swab tests.

Indeed, two studies found that people who develop more severe respiratory issues linked to COVID-19 have higher viral loads when admitted to the hospital relative to people with mild cases.

"As the pandemic slows down, more of the general population is getting tested, so you'll probably pick up more people with mild symptoms," Hodcroft said. "If you don't account for that, that could lead you to believe the virus has become less severe."

Adam Payne contributed reporting to this story.

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Coronavirus is not mutating to be weaker over time, genetics show - Business Insider - Business Insider