Monthly Archives: June 2017

A physician who splits his time between family medicine and health tech found himself in the role of a patient when he decided to investigate whether he had inherited genes that increased the likelihood he would develop kidney cancer. Dr Michael Dulin, who also works as Chief Medical Officer with data analytics business Tresata, recounted his patient journey at the HIMSS Precision Medicine Summit in Boston this week.

Family pictures punctuated Dulins story. Following the death of his father from kidney cancer, he looked back at his family tree and realized that several aunts and uncles had succumbed to kidney cancer or some other type of cancer.

I wanted to put a personal face on this because thats the goal today, Dulin. Think about being in my shoes. What would you do if this were your family history?

He recalled that he had a fun career serving as an engineer, a physiologist, primary care physician, data care redesign, He investigated doing genetic testing but with two kids in college, the cost was prohibitive.

I figured if anyone can handle genetic testing it was me. I should know what it means I should be able to handle the information.

He noted that 23andMes test provided some interesting revelations he is predisposed to having a hairy back but he didnt have any of the key disease states.

He eventually found another company doing more thorough genetic analysis one of which referred him to a genetic counselor when he requested it. Two years ago, when he sought the advice of a genetic counselor, the cost of doing a genetic test for the 29 genes known to cause kidney cancer was $14,500. Dulin, who already had two children in college, deemed the cost too high. But only a year later the cost had come down significantly for the same test. So he decided to go for it since the reduced price tag made getting the test a realistic option.

It came back and, shit! It was positive. I really didnt believe itwas going to be positive. Suddenly I wasnt a physician anymore or an executive anymore. I was mortal; I was someone who could die from kidney cancer and probably I would die from kidney cancer. I had never really thought how I would feel about it being positive. Right away I felt pretty guilty because I had this gene I had passed onto my two kids.

Dulin noted that his concern then turned to his electronic medical record which resided with his employer. Could this influence his employment? Would it be considered a pre-existing condition under the Affordable Care Act? What would be the negative impact on Dulin and his family for doing this genetic testing?

I left that day feeling pretty confused, sad, anxious and depressed. Its a pretty scary thing to have happen, he said.

In the days that followed he relied on PubMed and other resources at the University of North Carolina at Chapel Hill and read up on research for papillary renal cell cancer and what steps he could take to improve his health. He learned that people with a high body mass index had a greater chance of developing kidney cancer as did smokers but that [moderate] alcohol consumption could be beneficial, for instance.

Dulin said that one benefit of the experience was finding out that both of his children had tested negative for inheriting the gene. It was a moment that clearly brought great relief to him but was an unexpectedly emotional moment as he talked about it.

He also sought to reconnect with old friends and tick off a few items on his bucket list. But the experience gave him a better understanding of the anxiety and decisions patients in this situation face without the benefit of a medical background.

Photo: Andrzej Wojcicki, Getty Images

See the article here:
Physician shares genetic testing journey and gains a patient's perspective along the way - MedCity News

The patent is the first that Merck, a leader in genome editing, has received for CRISPR technology. Thepatent covers chromosomal integration, or cutting of the chromosomal sequence of eukaryotic cells(such as mammalian and plant cells)and insertion of an external or donor DNA sequence into those cells using CRISPR.

"Merck has developed an incredible tool to give scientists the ability to find new treatments and cures for conditions for which there are limited options, including cancer, rare diseases and chronic conditions, such as diabetes," said Udit Batra, Member of the Merck Executive Board and CEO,Life Science. "This patent decision recognizes our expertise in CRISPR technology - a body of knowledge that we are committed to grow."

Merck has patent filings for its insertion CRISPR method in Brazil, Canada, China, Europe, India, Israel, Japan, Singapore, South Korea and the U.S.

CRISPR genome-editing technology, which allows the precise modification of chromosomes in living cells, is advancing treatment options for some of the toughest medical conditions faced today. CRISPR applications are far-ranging - from identifying genes associated with cancer and rare diseases to reversing mutations that cause blindness.

Merck has a 14-year history in the genome-editing field. It was the first company to offer custom biomolecules for genome editing globally (TargeTron RNA-guided group II introns and CompoZr zinc finger nucleases), driving adoption of these techniques by researchers all over the world. Merck was also the first company to manufacture arrayed CRISPR libraries covering the entire human genome, accelerating cures for diseases by allowing scientists to explore more questions about root causes.

With Merck's CRISPR genomic integration technology, scientists can replace a disease-associated mutation with a beneficial or functional sequence, a method important for creation of disease models and gene therapy. Additionally, scientists can use the method to insert transgenes that label endogenous proteins for visual tracking within cells.

In May 2017, Merck announced that it had developed an alternative CRISPR genome-editing method called proxy-CRISPR. Unlike other systems, Merck's proxy-CRISPR technique can cut previously unreachable cell locations, making CRISPR more efficient, flexible and specific, and giving researchers more experimental options. Merck has filed several patent applications on its proxy-CRISPR technology, and those applications are just the latest of multiple CRISPR patent filings made by the company since 2012.

In addition to basic gene-editing research, Merck supports development of gene- and cell-based therapeutics and manufactures viral vectors. In 2016, Merck launched a genome-editing initiative aimed at advancing research in novel modalities -from genome editing to gene medicine manufacturing -through a dedicated team and enhanced resources, further solidifying the company's commitment to the field.

All Merck news releases are distributed by email at the same time they become available on the Merck website. Please go to http://www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.

About Merck Merck is a leading science and technology company in healthcare, life science and performance materials. Around 50,000 employees work to further develop technologies that improve and enhance life -from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD televisions. In 2016, Merck generated sales of 15 billion in 66 countries. Founded in 1668, Merck is the world's oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck holds the global rights to the"Merck"name and brand. The only exceptions are the United States and Canada, where the company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.

Photo -https://mma.prnewswire.com/media/522938/Merck_CRISPR_Patent.jpg

View original post here:
Merck Awarded its First CRISPR Patent by Australian Patent Office - TASS

June 13, 2017 UNC scientists discovered how the enzyme Set2 keeps gene transcription working properly when cells are under stress. Credit: Christ-claude Mowandza-ndinga

UNC School of Medicine researchers have cracked a long-standing mystery about an important enzyme found in virtually all organisms other than bacteria. The basic science finding may have implications for understanding cancer development and how to halt it.

Researchers have known that the enzyme Set2 is important for transcribing genes - the process of making strands of RNA from the DNA. Transcription is critical for making proteins and other functional molecules. But Set2's precise role in transcription hasn't been clear. Now, UNC scientists discovered that the enzyme is particularly important for keeping transcription working properly when cells are under stress. Without Set2, cells that become stressed through the lack of nutrients begin mis-transcribing genes in a way that prevents cells from adapting properly to the stress.

"We think this solves a mystery about the purpose of Set2, and we now understand much better how gene transcription is prevented from happening at the wrong place and time," said study senior author Brian Strahl, PhD, professor of biochemistry and biophysics and member of the UNC Lineberger Comprehensive Cancer Center.

Set2 enzymes in yeast and other lower organisms have close relatives in all animal species and plants. Its human cousin SETD2 is often found mutated in cancerous cells.

"These fundamental findings may help explain how SETD2 mutations could lead to inappropriate transcription within genes, which might then promote cancer initiation or progression," Strahl said. His team's research on SETD2 is ongoing.

The research, published in Cell Reports, involved collaboration between Strahl's laboratory and that of Ian J. Davis, MD, PhD, associate professor of pediatrics and genetics at the UNC School of Medicine and member of the UNC Lineberger Comprehensive Cancer Center.

The discovery comes 15 years after the first studies of Set2 by Strahl and others, who found that the enzyme works by attaching molecules known as methyl groups to a support protein - or histone - around which DNA is spooled.

This methyl-attaching process is called methylation. Research has shown in recent years that the particular histone methylation performed by Set2 serves as a quality control check on gene transcription.

Transcription of a gene should start at a precise spot at the beginning of a gene and then continue until the end in order to fully transcribe the RNA. But in the absence of histone methylation laid down by Set2, transcription begins at the wrong places in the middle of a gene instead of at the beginning. If that is allowed to happen, the production of "cryptic" RNA transcripts can then interfere with the normal expression of a gene. The mis-expression of our genetic material can result in diseases such as cancer.

Strahl's team thought Set2 might have something to do with these cryptic transcripts arising during stress. Previously, it was shown that Set2's histone-methylating activity has the effect of attracting another enzyme to clear away chemical tags in the middle of a gene that, otherwise, can lead to inappropriate new transcription from within that gene.

"But under typical laboratory conditions, the deletion of Set2 and the subsequent increase in cryptic transcripts didn't seem to harm cells very much," Strahl said.

Strahl's team then thought about cells under stress, which is what cells are like in disease states. His team conducted experiments to observe what happens in cells that don't have Set2 when vital nutrients are removed. In this stressed state, cells normally activate a complex set of gene expression programs to help cope with the reduced nutrient resources.

"Nutrient depletion more accurately mimics what yeast cells experience in the wild," Strahl said.

The scientists examined yeast cells that were deprived of nutrients, or were exposed to chemicals that reliably trigger the low-nutrient response. In these cells, not having Set2 proved to have major consequences.

"We found that this inappropriate transcription at the wrong place in genes exploded to high levels in stressed cells, and often interfered with the normal genes," Strahl said. "As a result, the normal changes in genes that help cells survive under low-nutrient conditions did not happen correctly, and the cells became extremely sick."

To Strahl and colleagues, the finding suggests that Set2 evolved to guard against harmful abnormal transcription in times of stress, when cells seem particularly vulnerable to this type of error. Why would cells be so vulnerable to cryptic transcription during the nutrient stress response? Strahl isn't sure. But his team suspects that when there's a sudden and widespread rearrangement of the molecular machinery of gene transcription, genes across the genome are left relatively open to inappropriate transcription.

"We found that a lot of the genes that show this crazy jump in cryptic transcription were not even related to the nutrient stress response," Strahl said. "It's as if there are genes throughout the genome that are just predisposed to this error, especially at this time when transcription is shifting dramatically."

Strahl and Davis and their colleagues plan further research to determine why cryptic transcription rises so dramatically during nutrient stress. They also intend to find out whether Set2 is important for safeguarding transcription during other types of cellular stress.

In addition, the scientists are now studying Set2's human counterpart, SETD2, which for unknown reasons is often mutated in tumor cells, especially in kidney cancers.

"It's possible that SETD2 normally works as a major tumor suppressor by preventing inappropriate transcription," Strahl said.

Explore further: Study pinpoints new role for enzyme in DNA repair, kidney cancer

More information: Cell Reports (2017). DOI: 10.1016/j.celrep.2017.05.057

Twelve years ago, UNC School of Medicine researcher Brian Strahl, PhD, found that a protein called Set2 plays a role in how yeast genes are expressed specifically how DNA gets transcribed into messenger RNA. Now his lab ...

The first step in gene expression is the exact copying of a segment of DNA by the enzyme known as RNA polymerase II, or pol II, into a mirror image RNA. Scientists recognize that pol II does not transcribe RNA via a smooth ...

Two opposing teams battle it out to regulate gene expression on the DNA playing field. One, the activators, keeps DNA open to enzymes that transcribe DNA into RNA. Their repressor opponents antagonize that effort by twisting ...

Clarification of how human blood vessels are constructed is desperately needed to advance regenerative medicine. A collaborative research group from Kumamoto University, Kyoto University, and the University of Tokyo in Japan ...

(Phys.org)An international team of researchers has found that gene transcription in an organism that has died continues for several days. In their paper published in the journal Royal Society Open Biology, the team describes ...

Scientists at the University of Birmingham have described a previously-unknown molecular mechanism that could lead to the genetic mutations seen in certain types of aggressive cancer cells, involving a cell's own transcription ...

There are many ways to make a living in a suitable climate but far fewer in a less suitable one. That may seem obvious for people living under various socio-economic stresses, but new research shows it also applies to the ...

Using research drones, thermal cameras and free images from Google Earth, two Duke University-led studies confirm that gray seals are making a comeback off the New England and eastern Canadian coasts.

A newly described protein could be an effective target for combatting drug-resistant malaria parasites. The protein, the transcription factor PfAP2-I, regulates a number of genes involved with the parasite's invasion of red ...

Adult females and males in a newly identified genus of Latin American praying mantises have evolved sharply different camouflage strategies, according to a Cleveland Museum of Natural History-led study published in the journal ...

Male birds tend to be better singers than femalesbut does the basis for this difference lie in the brain or in the syrinx, the bird equivalent of our larynx? The researchers behind a new study from The Auk: Ornithological ...

Animals living in areas where conditions are ideal for their species have less chance of evolving to cope with climate change, new research suggests.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read more from the original source:
Researchers show how a cancer gene protects genome organization - Phys.Org