October 13, 2022

Scientists at the University of Oxford have carried out a study to investigate whether and how peoples genes influence how strong an immune response they mount after vaccination with either the Oxford-AstraZeneca or Pfizer-BioNTech COVID-19 vaccine.

The study has been published in Nature Medicine.

The scientists analysed DNA samples from 1,190 participants whod enrolled in the University of Oxfords COVID-19 vaccine clinical trials, as well as from 1,677 adults who had enrolled on the Com-COV research programme, and from children who had participated in clinical trials for the Oxford-AstraZeneca vaccine.

Journalists dialled in to this briefing to hear from the scientists who did the study discuss aspects such as:

which genes in people determine how well their immune system responds to Covid vaccination?

which bits of the immune system seem to respond differently with different versions of these genes?

are there certain populations that tend to have specific versions of these genes?

what is the normal role of these genes?

are there implications?

Speakers included:

Prof Julian Knight, Professor of Genomic Medicine, Wellcome Centre for Human Genetics, University of Oxford

Dr Alexander Mentzer, Group Leader at the Wellcome Centre for Human Genetics, University of Oxford, and an Infectious Disease doctor

Dr Daniel OConnor, University Research Lecturer and Senior Bioinformatician, Oxford Vaccine Group, University of Oxford

This Briefing was accompanied by an SMC Roundup of comments.

Read more from the original source:

Study looking at human genetics and Covid vaccine immune responses - Science Media Centre

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia

Loc Yengo,Julia Sidorenko,Yang Wu,Jian Yang&Peter M. Visscher

Division of Endocrinology, Boston Childrens Hospital, Boston, MA, USA

Sailaja Vedantam,Eric Bartell,Jenkai Miao&Joel N. Hirschhorn

Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA

Sailaja Vedantam,Eric Bartell,Saori Sakaue,Jenkai Miao,Ronen E. Mukamel,George Hindy,Masahiro Kanai,Richa Saxena,Wei Zhou,Philip L. De Jager,Amit V. Khera,Samuli Ripatti,Cecilia M. Lindgren&Po-Ru Loh

William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

Eirini Marouli,Olga Giannakopoulou,Stavroula Kanoni,Ioanna Ntalla,Julia Ramirez,Helen R. Warren,Mark J. Caulfield,Patricia B. Munroe&Panos Deloukas

Harvard Medical School, Boston, MA, USA

Eric Bartell,Brian E. Cade,Saiju Pyarajan,Julie E. Buring,Paul L. Huang,Susan Redline,Paul M. Ridker,Daniel I. Chasman&Christopher J. ODonnell

Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

Saori Sakaue,Masato Akiyama,Masahiro Kanai,Yoichiro Kamatani&Yukinori Okada

Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan

Saori Sakaue,Masahiro Kanai&Yukinori Okada

Divisions of Genetics and Rheumatology, Brigham and Womens Hospital and Department of Medicine, Harvard Medical School, Boston, MA, USA

Saori Sakaue

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Marielisa Graff,Heather H. Highland,Rebecca Rohde,Yvonne M. Golightly,Anne E. Justice,Kari E. North&Kristin L. Young

COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

Anders U. Eliasen,Hans Bisgaard&Klaus Bnnelykke

Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Copenhagen, Denmark

Anders U. Eliasen

23andMe, Sunnyvale, CA, USA

Yunxuan Jiang,Gabriel Cuellar-Partida,Jingchunzi Shi,Gabriel Cuellar Partida&Adam Auton

Department of Veterans Affairs, Eastern Colorado Healthcare System, Aurora, CO, USA

Sridharan Raghavan

Division of Biomedical Informatics and Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

Sridharan Raghavan

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA

Joshua D. Arias,Moara Machado,Shengchao A. Li,Stephen J. Chanock,Stephen Chanock&Sonja I. Berndt

Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA

Sarah E. Graham,Whitney E. Hornsby,Tori L. Melendez&Cristen J. Willer

Division of Genetics, Department of Medicine, Brigham and Womens Hospital, Boston, MA, USA

Ronen E. Mukamel&Po-Ru Loh

Department of Medicine, Harvard Medical School, Boston, MA, USA

Ronen E. Mukamel,Josep M. Mercader&Po-Ru Loh

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Cassandra N. Spracklen,Laura M. Raffield&Karen L. Mohlke

Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA

Cassandra N. Spracklen

Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA

Xianyong Yin,Anne U. Jackson,Anita Pandit,Laura J. Scott,Michael Boehnke&Goncalo R. Abecasis

Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA

Shyh-Huei Chen

Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK

Teresa Ferreira&Cecilia M. Lindgren

Genetics of Complex Traits, College of Medicine and Health, University of Exeter, Exeter, UK

Yingjie Ji,Timothy M. Frayling&Andrew R. Wood

Center for Health Data Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Tugce Karaderi

Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK

Tugce Karaderi,Anuj Goel,Anubha Mahajan,Nigel W. Rayner,Hugh Watkins,Mark I. McCarthy&Cecilia M. Lindgren

Nuffield Department of Population Health, University of Oxford, Oxford, UK

Kuang Lin,Deborah E. Malden,Zammy Fairhurst-Hunter,Jun Liu,Iona Y. Millwood,Zhengming Chen,Cornelia M. van Duijn&Robin G. Walters

Institute of Genomics, Estonian Genome Centre, University of Tartu, Tartu, Estonia

Kreete Lll,Katri Prna,Reedik Mgi,Andres Metspalu&Tnu Esko

Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

Carolina Medina-Gomez,Andre G. Uitterlinden,Nathalie Van der Velde&Fernando Rivadeneira

Division of Biostatistics and Epidemiology, RTI International, Durham, NC, USA

Amy Moore

Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland

Sina Reger,Aaron F. McDaid&Zoltan Kutalik

Swiss Institute of Bioinformatics, Lausanne, Switzerland

Sina Reger,Aaron F. McDaid&Zoltan Kutalik

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore

Xueling Sim,Jin-Fang Chai,Rob M. van Dam&E. Shyong Tai

Department of Psychology, University of Minnesota, Minneapolis, MN, USA

Scott Vrieze,Hannah Young,William G. Iacono&Matt McGue

Steno Diabetes Center Copenhagen, Herlev, Denmark

Tarunveer S. Ahluwalia

Department of Biology, The Bioinformatics Center, University of Copenhagen, Copenhagen, Denmark

Tarunveer S. Ahluwalia

Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Masato Akiyama

Department of Family Medicine, University of California, San Diego, La Jolla, CA, USA

Matthew A. Allison

Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

Marcus Alvarez&Pivi Pajukanta

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Mette K. Andersen,Jette Bork-Jensen,Anette P. Gjesing,Anna Jonsson,Niels Grarup,Torben Hansen,Oluf Pedersen&Ruth J. F. Loos

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

Alireza Ani,Ilja M. Nolte,Katri Prna,Peter J. van der Most,Tian Xie,Harold Snieder&Judith M. Vonk

Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran

Alireza Ani

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Copenhagen, Denmark

Vivek Appadurai,Thomas F. Hansen&Thomas M. Werge

Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Liubov Arbeeva,Yvonne M. Golightly&Amanda E. Nelson

Genomic Research on Complex diseases (GRC-Group), CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India

Seema Bhaskar,Suraj S. Nongmaithem,Divya Sri Priyanka Tallapragada&Giriraj R. Chandak

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA

Lawrence F. Bielak,Albert V. Smith,Jennifer A. Smith,Wei Zhao,Sharon L. R. Kardia&Patricia A. Peyser

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland

Sailalitha Bollepalli,Aki S. Havulinna,Sanni E. Ruotsalainen,Jaakko Kaprio,Samuli Ripatti,Tiinamaija Tuomi&Elisabeth Widen

Molecular Genetics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

Lori L. Bonnycastle&Francis S. Collins

Center for Applied Genomics, Childrens Hospital of Philadelphia, Philadelphia, PA, USA

Jonathan P. Bradfield,Struan F. A. Grant&Hakon Hakonarson

Quantinuum Research, Wayne, PA, USA

Jonathan P. Bradfield

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A saturated map of common genetic variants associated with human height - Nature.com

In 1952, Nobel-prize winner Dr. Peter Medawar put forward the hypothesis that aging processes may be a result of evolutions natural selection not having that much to say about people past their child-bearing years.

A new study finds fresh support for Medawars hypothesis in an analysis of how roughly 20,000 human genes are expressed as we age.

The study suggests that our genes are less of an influence as we get older.

Study senior author Dr. Peter Sudmant, assistant professor in integrative biology at the University of California Berkeley tells Berkeley News, Almost all human common diseases are diseases of aging: Alzheimers, cancers, heart disease, diabetes.

Massive amounts of public resources have gone into identifying genetic variants that predispose you to these diseases. What our study is showing is that, well, actually, as you get older, genes kind of matter less for your gene expression, says Sudmant.

The study is published in Nature Communications.

Dr. Sudmant summarized Medawars hypothesis for Medical News Today:

Genes that are turned on when we are young are more constrained by evolution because they are critical to making sure we survive to reproduce, while genes expressed after we reach reproductive age are under less evolutionary pressure.

Dr. Giuseppe Passarino, professor of genetics at the University of Calabria in Italy, who was not involved in the study, explained to MNT how this works:

It is evident that in order to have more children, you need to survive and to be fit [long enough to] reproduce yourself. To get this goal, you need to have no diseases while you are young, to be able to find food, to get a partner.

Genes which are expressed during the first part of your lifetime are highly selected, and then only the best ones survive. Dr. Giuseppe Passarino

Evolution is based on the fact that individuals who have better fitness have more children. Thus, their genotypes will spread in the population more than those of subjects who have [fewer] children, Dr. Passarino added.

The researchers retrieved gene expression data for 27 different types of body tissues in almost 950 people from the GTEx web portal. Individuals were categorized as young if they were less than 55 years of age, and old if they were 55 or over.

In their analysis, the researchers found that genetics exerts about the same amount of influence over gene expression in almost all of our tissues until we cross into the old bracket.

At that point, aging plays a much more influential role for five critical tissue types blood, colon, arteries, esophagus, and fat tissues than does genetics.

As an influence on gene expression in the study, aging refers to the universal, progressive cellular aging processes associated with advancing years.

In our study, we found in five high proliferation tissues (blood, colon, etc.), [that] these highly constrained genes are actually turned on late in life. These genes tend to be those that are involved in cell division and proliferation, and consequently, in cancer. Dr. Peter Sudmant

While it would theoretically be helpful if evolution would help select genes that keep us healthy even after we reproduce, according to Dr. Sudmant:

The limit of evolution here is that, late in life, you really should not have these sorts of genes turned on, and having them turned on actually makes you susceptible to cancer. However, because these are cell types in your body that need to keep turning over blood! there is no other option.

Hence, aging and environmental factors are more influential in gene expression for these critical tissues.

In the study, environmental influences include factors not directly associated with those processes: the quality of the air and water we breathe and eat, our diet, and also our level of physical exercise.

The study finds that environmental factors account for about a third of gene expression in older people.

This [study] does not imply that genetics is not important for aging. There are many studies showing that the similarities between relatives regarding the quality of aging (presence of diseases or inabilities) are very high. In fact, although the genes expressed later in life are not selected, still they are important for our life. Dr. Giuseppe Passarino

In other words, we are equipped with highly selected alleles for the first part of our life and with alleles [that] are less selected for the second part. However, in both cases, our phenotype is based on our genes, Dr. Passarino added.

According to Dr. Passarino, to better understand the complexity of how humans age and to learn how to slow down this process, researchers need to study the genes expressed later in life and improve them.

One option may be to see how the genetic machinery works in long-lived subjects, and try to modulate the machinery of others accordingly, said Dr. Passarino.

For instance, it has been observed that long-lived subjects have limited ability to use proteins or sugar. Thus, we can use a limited amount of proteins and sugar to modulate our organism machinery as if we were equipped with the same genes of long-lived subjects, he elaborated.

When we do studies to identify the genetics underlying disease, we often end up with many genes that we could potentially target. Our study now quantifies how age impacts the expression of genes in the population. We argue that age-associated genes might be better therapeutic targets than the ones that vary in their expression as a function of human genetics, Dr. Sudmant said.

We think that genes that show consistence in age-associated changes in expression in humans are potentially really interesting targets to follow up on! he concluded.

Read the original post:

Age vs. DNA: Which has more influence on how humans age? - Medical News Today

Nucleome Therapeutics raises oversubscribed 37.5 million Series A financing to decode the dark matter of the human genome and deliver first-in-class precision medicines

Oxford, UK, 19 October 2022 Nucleome Therapeutics Limited, (Nucleome or the Company), a biotechnology company decoding the dark matter of the human genome to discover first-in-class precision medicines, today announces it has closed an oversubscribed 37.5 million Series A financing round. The funds will be used to advance the Company's autoimmune disease programmes, fuel expansion of its dark genome atlas and further develop its pioneering platform.

The financing was led by new investor M Ventures, the strategic, corporate venture capital arm of Merck KGaA, with participation from Johnson and Johnson Innovation-JJDC, Inc. (JJDC), the strategic venture capital arm of Johnson & Johnson; Pfizer Ventures, the venture group of Pfizer; British Patient Capital, through its Future Fund: Breakthrough programme; and founding investor Oxford Science Enterprises.

Nucleome has the unique ability to discover and validate first-in-class targets through genetics, by investigating the dark region of the human genome, which does not encode for proteins but contains 90% of disease-associated genetic changes. Understanding the role of these genetic variants has been a long-standing challenge, hindering the translation of the human genome into useful drug discovery insights.

Nucleomes breakthrough platform combines pioneering 3D genome technology and machine learning to shed light on these variants by directly linking genes to diseases and mapping pathways with unprecedented precision for drug discovery.

We have already made significant progress by mapping genes to genetics in a number of human immune cell types and discovering the first wave of potential first-in-class autoimmune disease targets, said Dr Danuta Jeziorska, Chief Executive Officer and Co-founder of Nucleome Therapeutics. The completion of this oversubscribed round with such a high-calibre group of global life science investors is a recognition of the significance of Nucleomes platform and its potential to support the development of an exciting portfolio of first-in-class targets for autoimmune diseases.

Dr Bauke Anninga, Principal at M Ventures, commented: Nucleomes differentiated platform technology has the potential to fundamentally shift the way we discover and develop precision medicines. Unlocking the value of the largely unexplored territory of the genome can lead to the identification of high-value drug targets. Nucleomes platform adds 3D genomic information to a wealth of available genomic data, uncovering a new dimension of information that is disease as well as cell type-specific. We are excited to lead this financing, and alongside our co-investors, partner with Nucleomes exceptional team to advance their target and drug discovery programmes to bring transformative treatments to patients.

Dr Jonathan Hepple, Non-executive Director at Nucleome and Advisor to Oxford Science Enterprises, added:Since its founding in 2019, Nucleome has advanced to become a leader in 3D genomics analysis. Publications in high-impact journals have validated its groundbreaking technology and ability to identify new drug targets where other technologies fall short. With a highly experienced team, this fundraising, backed by an impressive syndicate of world-class investors, will allow Nucleome to explore the dark genome and develop its exciting pipeline of potential drug targets. Oxford Science Enterprises is proud to have supported the Company since its inception and continues to do so, and we look forward to working with the team through this exciting time of growth.

Ends

For more information, please contact:

Nucleome TherapeuticsDr Danuta Jeziorska, Chief Executive Officer & Foundercontact@nucleome.com

Consilium Strategic CommunicationsMary-Jane Elliott/Sukaina Virji/Stella Lempidaki Nucleome@consilium-comms.com

About Nucleome Therapeutics Nucleome Therapeutics is decoding the dark matter of the human genome to uncover novel ways to treat disease. The dark genome holds more than 90% of disease-linked genetic variants whose value remains untapped, representing a significant opportunity for drug discovery and development. The Company has the unique ability to link these variants to gene function and precisely map disease pathways. Nucleomes cell type-specific platform creates high resolution 3D genome structure maps and enables variant functional validation at scale in primary cell types, enabling the discovery and development of novel, better and safer drugs. The initial focus of the company is on lymphocytes and related autoimmune disease. Nucleomes ambition is to build a robust pipeline of drug assets, with corresponding biomarkers. Nucleome Therapeutics was founded by leading experts in gene regulation from the University of Oxford. For more information, please visit http://www.nucleome.com.

About M Ventures M Ventures is the strategic, corporate venture capital arm of Merck KGaA, Darmstadt, Germany. From its headquarters in the Netherlands and offices in Germany, USA and Israel, M Ventures invests globally in transformational ideas driven by innovative entrepreneurs. Taking an active role in its portfolio companies, M Ventures teams up with management teams and co-investors to translate scientific discoveries into commercial success. M Ventures focuses on identifying and financing novel solutions to some of the most difficult challenges, through company creation and equity investments in fields that will impact the vitality and sustainability of Merck KGaA, Darmstadt, Germany 's current and future businesses. For more information, visit http://www.m-ventures.com.

About Pfizer Ventures Pfizer Ventures, the venture capital arm of Pfizer Inc., was founded in 2004 and invests for return in areas of current or future strategic interest to Pfizer. Pfizer Ventures seeks to remain at the forefront of life science advances, looking to identify and invest in emerging companies that are developing transformative medicines and technologies that have the potential to enhance Pfizers pipeline and shape the future of our industry.

About British Patient Capital

British Patient Capital is the trading name of British Patient Capital Limited, a wholly-owned commercial subsidiary of British Business Bank plc, the UK governments economic development bank. It forms part of the British Business Banks plcs commercial arm. Its mission is to enable long-term investment in innovative firms led by ambitious entrepreneurs who want to build large scale businesses. Launched in June 2018, British Patient Capital has 2.5bn to invest over 10 years in venture and venture growth capital to support high growth potential innovative UK businesses in accessing the long-term financing they require to scale up. Find out more at britishpatientcapital.co.uk.

About Oxford Science Enterprises Oxford Science Enterprises (OSE) is an independent, billion-pound investment company, created in 2015 to found, fund and build transformational businesses via its unique partnership with the University of Oxford, the world's #1 research university.This partnership enables OSE to work with the brightest academic minds tackling the world's toughest challenges and guarantees unrivalled access to their scientific research.In collaboration with its global network of entrepreneurs and advisers, OSE shapes and nurtures complex ideas into successful businesses, while targeting attractive returns for shareholders.Actively focused on a core portfolio of around 40 companies spanning three high-growth, high-impact sectors Life Sciences, Health Tech, and Deep Tech the company adopts a flexible, long-term investment approach, recognising the path from ground-breaking research to global markets takes time and resilience.To date, OSE has invested 0.5 billion in over 80 ambitious companies built on Oxford science.A key player in Oxford's entrepreneurial ecosystem, OSE is highly motivated to foster an environment that catalyses pioneering research and steers it to commercial success.Find out more:oxfordscienceenterprises.com|Twitter|LinkedIn

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Nucleome Therapeutics raises oversubscribed 37.5 million Series A financing to decode the dark matter of the human genome and deliver first-in-class...

image:Katie Pollard is recognized by the National Academy of Medicine for discovering fast-evolving regions of the human genome and for creating open-source software used by scientists worldwide. view more

Credit: Photo: Michael Short/Gladstone Institutes

SAN FRANCISCO, CAData scientist and statistician Katie Pollard, PhD, director of the Gladstone Institute of Data Science and Biotechnology, has been elected to the National Academy of Medicine (NAM), one of the highest honors in health and medicine. Through its election process, the Academy recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.

Pollard is perhaps best known for developing a novel statistical approach to identify human accelerated regions (HARs), which are stretches of DNA that rapidly changed when humans evolved from primate ancestors. Many of these regions of the human genome help determine when and where important genesincluding those associated with diseasesare turned on or off.

Pollard is also being recognized for the creation of statistical models and open-source bioinformatics software, which are used by researchers worldwide to investigate gene activity, genome evolution, and the microbiome (the collection of microbes found in the human gut).

As a statistician, I am honored that the National Academy of Medicine and my nominators value our contributionsand the contributions of data scientists more broadlyto biomedical research and medicine, says Pollard. I love coding and math, but what really motivates me is using these methods to understand how our bodies work and how they break in disease.

Pollard, who is also a professor in the Department of Epidemiology and Biostatistics at UC San Francisco and an investigator at the Chan Zuckerberg Biohub, entered graduate school at the University of California, Berkeley, interested in using math and statistics for public health applications. She was moving from classwork to research when the human genome was sequenced for the first time.

I immediately became interested in using the genome sequence to measure differences in gene activity between tissues and disease states, such as in tumors versus nearby healthy tissue, she recalls. I also wanted to develop statistical methods that could help me, and other researchers, get reliable results from the unprecedently large arrays of genomic data being produced.

Since then, Pollard and her lab have made critical contributions to several other research areas, including decoding how genomes work by using comparative genomics; creating statistical models, open-source bioinformatics software, and machine-learning frameworks to better understand the human genome; and developing analytical tools to study the human microbiome.

Driving Medical Research with Bioinformatic Approaches

As Pollard started her postdoctoral work, the chimpanzee genome was sequenced. Because she had studied anthropology (including primatology) as an undergraduate, she understood the importance and potential applications of the new information, and performed one of the first genome-wide comparisons of human and chimpanzee DNA. That work led to the discovery of HARs.

HARs are short pieces of DNA where chimpanzees and other non-human mammals have nearly identical sequences, she explains. But the human HARs are very different from the chimps, which makes HARs exciting candidates for understanding traits that are unique to humans, such as spoken language, HIV susceptibility, and psychiatric diseases.

After scientists had been trying to figure out the function of HARs for nearly a decade, Pollard and her team made a significant breakthrough by using an innovative approach inspired by the fields of bioinformatics, stem cell biology, and genomics.

They discovered that the vast majority of HARs are not genes, but rather enhancers that turn the activity of nearby genes up or down. They also found that many HARs control genes involved in brain development and in psychiatric diseases that are uniquely human, such as autism and schizophrenia.

In parallel, for the past 15 years, Pollards team has been developing new ways to analyze the hundreds of species of microbes that grow inside the human gut, which play many roles in health and disease.Their breakthroughs could lead to the development of therapies to maintain or improve gut health. They are also helping set the stage for using the microbiome in precision medicine.

To make these discoveries, we first had to create the right bioinformatics tools to tackle the questions we wanted to answer, says Pollard. We then applied our tools to massive analyses of terabytes of publicly available data, bringing together datasets that were not originally collected for the same purpose. And we used these datasets to ask new questions beyond what was analyzed in the original studies.

She helped create several computational methods to better analyze typical datasets, including an approach that allows researchers to carry out bigger and more precise analyses of the microbiome than ever before. Their approaches are also faster and cheaper than previous technologies, making them accessible to most labsnot only the ones that can afford high-performance computing power.

To Pollard, this is one of the most crucial aspects of technology development: creating tools that can be shared with, and used by, as many scientists and students as possible. Thats why shes such a strong advocate of open science, and a world leader in open-source bioinformatics software.

The machine-learning tools and statistical methods we develop can be used to study a wide range of diseases, says Pollard. Its important to me that they can be made available to anyone who needs them, so that we can open the door to important discoveries by researchers all around the world, across a variety of fields.

Expanding the Role of Data Science

Looking ahead, Pollard would like to help expand the role of data science in modern biomedical research. Rather than its current function of supporting the analysis of experimental research that has already been conducted, she would like to see data science setting the direction of experimentation and technology development.

What Im most excited about is using predictive models to drive experiments and the development of new tools and technologies, she says. Data scientists being in the drivers seat will also ensure that we are designing the experiments and machines that best address the questions we want to ask down the line.

Pollard earned her BA at Pomona College and her Masters degree and PhD in biostatistics from UC Berkeley. She is a Fellow of the American Institute for Medical and Biological Engineering, the California Academy of Sciences, and the International Society for Computational Biology. She is also a member of the American Society of Human Genetics and the American Statistical Association.

Pollards election was announced on October 17, 2022, by the NAM, which is part of the congressionally chartered National Academy of Sciencesa group of private, nonprofit institutions that provide objective advice on matters of science, technology, and health.

Pollard joins seven fellow NAM members from Gladstone Institutes: Jennifer Doudna, PhD, senior investigator; Warner Greene, MD, PhD, senior investigator; Robert W. Mahley, MD, PhD, senior investigator, president emeritus, and Gladstone founder; Lennart Mucke, MD, senior investigator and director of the Gladstone Institute of Neurological Disease; Deepak Srivastava, MD, senior investigator and president of Gladstone; R. Sanders Williams, MD, former Gladstone president; and Shinya Yamanaka, MD, PhD, senior investigator.

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Gladstone data scientist elected to the National Academy of Medicine - EurekAlert

LAWRENCE, KANSAS A University of Kansas researcher is taking a novel approach to the prolific problem of opioid addiction in America. With a $2.3 million grant from the National Institute on Drug Abuse, Zijun Wangwill research the implications of the DNA break-and-repair process in opioid use disorder.

Wangs work is based on the premise that opioid addiction is a psychiatric disorder caused by molecular changes in the brain that alter behavior.

Drug addiction is not a moral failing, said Wang, assistant professor of pharmacology & toxicology. In terms of addiction, the reward pathway in the brain is hijacked by repeated drug exposure. Drug-induced structural changes result in many abnormal behaviors, including reduced inhibitory control that prevents someone from avoiding behaviors with negative consequences.

The human genome consists of more than 3 billion base pairs of DNA, which contain more than 20,000 genes. This genetic material is used in complex biochemical processes in human cell function, development and replication. Wang said the genome is under attack from a variety of sources. Normally, the DNA repair process can overcome these attacks, but repeated drug exposure can disrupt this process, changing gene expression, cell function and leading to abnormal drug addiction-related behaviors.

Wangs research focuses on the DNA break-and-repair processes disrupted by addiction. Ultimately, Wang said she aims to help the genome maintain a normal or healthy environment in the cell and identify a potential therapy for these patients to prevent them from relapsing to drug use.

The therapeutic approach needed to target DNA breaks has yet to be developed but could come in the form of a drug or gene therapy. Right now, we are still at the initial step, but eventually we want to provide novel insight for the development of future therapies, Wang said. The first thing we want to do is have a clearer idea of the neurobiology underlying this opioid addiction.

The work on this grant addresses a critical issue: what causes drug users to relapse to using drugs after they manage to quit drug use, said Nancy Muma, chair of the Department of Pharmacology & Toxicology. Zijun has developed a novel approach to determine if the problem is damage to the persons genes. If this is the case, then future research can begin to address ways to mitigate the damage to the genes to prevent or reduce relapse.

This is novel research that no one else has done before, Wang said. How does DNA damage contribute to opioid addiction? We're trying to make a link between those. At the end of the day, we want to find a treatment that can reduce drug-seeking behavior.

This grant is funded through the Genetics or Epigenetics of Substance Use Disorders Avenir Award program that supports highly creative early-stage investigators proposing innovative studies that open new areas of research for the genetics or epigenetics of addiction.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Pharmacy researcher earns $2.3 million NIH award to study opioid addiction - EurekAlert

Researchers have found that most Nepali populations derivetheir maternal ancestry from lowland populations than highlanders.

Scientists from Hyderabad-based CSIR-Centre for Cellular and Molecular Biology (CCMB), Tribhuvan University of Nepal, DST-Birbal Sahni Institute of Palaeosciences in Lucknow, and Banaras Hindu University of Varanasi collaborated in what is termed as the first largest study on the Nepalese populations to trace their origins.

Investigators analysed mitochondrial DNA sequences of 999 individuals from different ethnic groups of Nepalincluding Newar, Magar, Sherpa, Brahmin, Tharu, Tamang, and populations from Kathmandu and Eastern Nepal.

Dr K Thangaraj from CCMB who led the research told DH that some of the Nepalese were found to have ancestral links to Brahmins and Thakurs of Uttarakhand and Uttar Pradesh.

Located at a crossroads in the Himalayan region, Nepal offers a unique ground to understand south and east Asian genetic ancestry. The Himalayan mountains range of Nepal has served as a geographical barrier to population migration, while at the same time, its valleys have been avenues for trade and exchange.

Despite the long-term economic and cultural importance of the Himalayan trade routes, very little is known about the early population history of the region.

The results of the study have now helped the researchers fill several critical gaps in the history and past demographic events that shaped the present Nepalese genetic diversity.

Our study showed that the ancient genetic make-up of the Nepalese was gradually transformed by various mixing episodes along the migratory path to Nepal. The carriers of some mitochondrial lineages may have crossed the Himalayas into Nepal, most likely via southeast Tibet, between 3.8 and six thousand years ago, said Rajdip Basnet, the first author of the study from Tribhuvan University.

The findings were published recently in the journal Human Genetics.

Tibeto-Burman communities like Newar and Magar revealed a distinct population history than contemporary high-altitude Tibetans/Sherpas. This study, using history, archaeological and genetic information, has helped us in understanding the population history of Tibeto-Burman communities of Nepal, said Dr Niraj Rai, one of the authors from DST- Birbal Sahni Institute of Palaeosciences.

The cultural ties of Nepal with India and Tibet reflected in their genomic ancestry, said Gyaneshwer Chaubey, a professor from Banaras Hindu University and co-author of the study.

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First largest study of Nepalis shows genealogy links with Thakurs, Brahmins of north India - Deccan Herald

Top-line phase 2 data evaluating drug candidates for treating the rare disease phenylketonuria (PKU) was announced this morning. The study compared the efficacy of 2 strains of a non-systemically absorbed drug candidate in patients with the diagnosis.

While both strains, SYNB1618 and SYNB1934, demonstrated clinically meaningful reductions in fasting plasma phenylalanine (Phe) levels, SYNB1934 will be the candidate investigated in the anticipated 2023 phase 3 clinical trial.

The rare inherited disorder is caused by a disruption in the phenylalanine hydroxylase (PAH) gene, which helps create the enzyme necessary to break down phenylalanine. As a result the phenylalanine amino acid accumulates in the body which can be dangerous and lead to serious health problems.

These patients can experience intellectual limitations in areas of thinking, understanding and communicating as well as other major health problems.Early intervention is crucialscreening for this disease is typically done at birth.

At this time there's no cure, so patients with the condition are instructed to restrict their diet to avoid foods that can increase the phenylalanine build up, typically found in high-protein foods. However, some individuals can be less restrictive if they're taking medications that are effective for them.

PKU continues to be a very challenging disease for patients, with many in need of new treatment options, Jerry Vockley, MD, PhD, Professor of Human Genetics,University of Pittsburgh, and lead investigator on the phase 2 Synpheny-1 study said in a statement. It is very promising to see these results and the potential benefits of a new, orally administered investigational product that can meaningfully lower Phe in patients with PKU.

The Synpheny-1 study was a phase 2, open-label, 28-day clinical trial that assessed the safety, tolerability and efficacy of SYNB1618 and SYNB1934 in 20 adult patients with phenylketonuria. The primary endpoint was the change in area under the curve (AUC) of plasma levels of labeled D5-phenylalanine (D5-Phe) following a meal challenge before and after the treatment period. Investigators carefully managed the patients' dietary intake to replicate their routine protein and Phe consumption.

Each candidate's ability to mitigate Phe properly was examined as the administered dose regimen was increased over 15 days of treatment and then stayed consistent at a dose of 1x1012live cells for the second half of the treatment period. Secondary endpoints included change in fasting levels of plasma Phe from baseline, incidence of treatment-emergent adverse events (TEAEs), and the levels of additional strain-specific metabolites plasma D5-TCA and urinary D5-5A.

Patients enrolled in the study had a Phe level above 600 mol/L at screening despite treatment with diet and/or sapropterin. A total of 11 patients were included in the SYNB1618 arm and with 9 in the SYNB1934 arm. At the conclusion of the investigation, 10 patients completed the SYNB1618 arm and 5 patients completed the SYNB1934 arm.

The mean change from baseline at day 14 in fasting plasma Phe was -20% for those in SYNB1618 treatment and -34% for SYNB1934. Of the patients who completed the trial, 60% had a response greater than 20% Phe reduction by day 7 or day 14, with 6 of the 10 patients dosed with SYNB1618 and 3 of the 5 dosed with SYNB1934 meeting the criteria.

No serious adverse events were reported and the mild-moderate adverse events were predominantly gastrointestinal.

The robust plasma Phe reduction demonstrated by SYNB1934 indicates that it has potential to be a transformative treatment for patients with PKU,Aoife Brennan, MB, ChB,Synlogic President, Chief Executive Officer stated. I would like to thank the patients, clinicians and staff of our investigational sites who made this study possible. We look forward to further collaboration as we initiate our Phase 3 pivotal study, with the goal of bringing this potentially life-changing innovation in the treatment of PKU to patients.

Developing company Synlogichas confirmed these data supported the decision to continue with SYNB1934 as the drug candidate advancing to a phase 3 pivotal study which is expected to begin in the first half of 2023.

Read more here:

New Rare Disease Therapy Effectively Lowers Plasma Phe in Patients with PKU - MD Magazine