NIH Challenge Grants Include Bait for Epigenetics Researchers


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Yesterday the National Institutes of Health (NIH) released the Request for Applications (RFA) for the NIH Challenge Grants in Health and Science Research. The omnibus includes a list of 15 topic areas for proposals:

1. Behavior, Behavior Change, and Prevention
2. Bioethics
3. Biomarker Discovery and Validation
4. Clinical Research
5. Comparative Effectiveness Research (CER)
6. Enabling Technologies
7. Enhancing Clinical Trials
8. Genomics
9. Health Disparities
10. Information Technology for Processing Health Care Data
11. Regenerative Medicine
12. Science, Technology, Engineering and Mathematics Education
13. Smart Biomaterials – Theranostics
14. Stem Cells
15. Translational Science

The omnibus PDF (link, 1.7 MB) also includes specific topic areas of interest, as well as topics that are considered the highest priority by individual centers.

Among the specific topic areas are several that could be applicable to researchers within the broad spectrum of epigenetics research:

01-DA-111 Approaches to study the interactions among individual behaviors, social and physical environments, and genetic/epigenetic processes during critical developmental periods. NIDA is soliciting research that integrates environmental and developmental variables with genotypic information in order to permit comprehensive model-building and hypothesis testing for determining genetic, environmental, and developmental contributions to substance abuse and related phenotypes.

01-OD(OBSSR)-102* Methods for studying the interactions among behaviors, environments, and genetic/epigenetic processes. Research is needed to develop analytic methods, systems science approaches, or computational models designed to address the interactions among individual behaviors, social and physical environments and genetic/epigenetic processes during critical developmental periods and over time. This research is essential to incorporating the dynamic complexity of behavior and environments in the study of gene-environment interactions in health.

02-DK-101 Ethical issues related to genetic and epigenetic information. Genotype and genome-wide association studies, as well as the large databases containing this information for many individuals create a series of challenging ethical issues. In genome wide epigenetic studies have the potential to identify specific environmental exposures linked to genotyped individuals. Relevant studies will address issues such as recontact, return of research results and incidental findings, informed consent in the context of possible identifiability, and implications for related individuals for diseases that fall within the scope of the NIDDK mission.

02-OD-101 Bioethical concerns unique to epigenomic research. Emerging evidence suggests that epigenetic changes may have an important role in a variety of diseases. Although our understanding of the bioethics of genomic studies is mature, our understanding of the bioethics of epigenomic studies is very much in its infancy. Specific environmental exposures (use of illicit drugs or alcohol, HIV infection, psychosocial stress, etc) or disease states (depression, HIV infection status, etc) may be correlated with specific epigenomic changes. Thus epigenomic research may lead to unique and unanticipated bioethical challenges that must be overcome. Studies exploring bioethical concerns unique to epigenomic research would identify unanticipated ethical problems and help identify appropriate solutions to be sure human subjects involved in epigenomic research are properly protected.

03-OD-101 Use of epigenetic signatures in blood cells to predict disease. Although epigenomic changes appear to be important in many diseases, disease diagnosis may be quite challenging if epigenomic analysis of tissues that are not readily accessible (brain, heart, etc) is required. Blood cells are readily accessible and could serve as powerful “sentinels” or biomarkers for a variety of complex diseases. Characterization of epigenomic signatures in blood cells in a variety of disease situations could lead to the development of entirely new non-invasive diagnostic strategies.

06-AR-103 Systems Biology for Skin and Rheumatic Diseases. Expansion of Merck’s proposed Integrative Bionetwork Community to include skin biology and diseases and rheumatic diseases. Merck has proposed to make their database of phenotypic data and genetics available to the public. While it is not clear what this database currently contains, in the area of skin biology/diseases and rheumatic diseases, there are already efforts by several NIAMS-supported research groups to identify the genetic basis of several diseases (e.g. psoriasis, vitiligo, and alopecia areata) through GWAS and to link expression data with the genetics. Similar efforts are ongoing in rheumatic diseases. It would be useful to extend the dataset by the addition of genome-wide epigenetics data and a catalogue of microRNAs identified by high throughput sequencing technologies. The data could also be extended through the addition of more diseases as well as the effects of treatment. There may also be some benefit to include stages of skin development and epidermal differentiation.

06-DA-103 Identification of chemical modulators of epigenetic regulators. There are a limited number of pharmacological agents available to manipulate the in vivo activity of most epigenetic modifying enzymes, effector molecules, etc. High-throughput small- molecule screening strategies targeted at specific epigenetic regulatory molecules could identify chemical reagents targeting a broad range of epigenetic regulatory molecules. These high impact reagents have the potential to transform the way epigeneticists conduct in vivo disease research.

06-HL-108 Develop new informatics techniques for integrative analysis of genomic and epigenomic data. Much of the complex interplay between genetic and environmental risk factors for disease likely occurs through the interactive regulation of gene expression by both genotype and epigenetic markings of the genome. Epigenetic tags such as cytosine methylation and histone tail modifications, which modulate chromatin structure and function thereby affecting gene expression, are associated with environmental toxicities and are well documented. An integrated analysis of gene expression regulation, with simultaneous consideration of both genetic and epigenetic characteristics and of the interactions between these factors, is essential for understanding the complex pathobiology of chronic heart, lung, and blood diseases. New computational and informatics techniques are needed to allow such analyses.

06-NS-105 Importing important technologies into neuroscience. The challenge is to capitalize on existing knowledge and technologies from other scientific disciplines (e.g. applied physics, nanotechnology, cancer biology, and immunology) to catalyze progress in basic and clinical neuroscience (e.g. cell signaling or cell cycle control mechanisms in neurodegeneration, inflammation in neurological disease, epigenetics in neural development, etc.). Proposals will also be considered that seek to validate, in neurological systems, technologies originally developed for use in other biological systems.

There are also many more topics listed that are very applicable for epigenetics researchers. So, if you have some time to crank out a grant proposal, you have 53 days and counting…

(HT: DrugMonkey)

Newsweek: Transgenerational epigenetics is “the new Lamarckism”


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A recent article in Newsweek from science writer Sharon Begley reports on “the new Lamarckism,” citing studies from epigenetics researchers, including Emma Whitelaw. The article seems to be all about transgenerational epigenetics, but rather than ever use the word “epigenetics,” the favored term is “the new Lamarckism.” Link

But evidence for the new Lamarckism is strong enough to say the last word on inheritance and evolution has not been written.

My guess is that Begley was intent on building up controversy in her opening that seemed to be criticizing evolution during Darwin’s big 200/150 year. And in that regard, she piqued the interest of one of the most popular science bloggers, PZ Myers, who criticized the article in a post on his blog–sending tons of traffic to Newsweek.

It’s very cool stuff, but evolutionary biologists are about as shocked by this as they are by the idea that malnourished mothers have underweight babies. That environmental influences can have multi-generational effects, and that developmental programs can cue off of the history of the germ line, is not a new idea, especially among developmental biologists.

One of the problems with calling epigenetics “the new Lamarckism” is that it can have the connotation that the field is going the way of Lamarckism, or that geneticists are unable to account for (or are afraid of acknowledging) these strange phenomena. In truth, geneticists are aware of these phenomena, and are eager to see what mechanism is at play in the inheritance of these traits across generations–whether it be methylation, small RNAs, or a host of other possibilities.

But no one in science is crying over the fact that epigenetics is uncovering more details about how disease is acquired or traits inherited.

Epigenetics & Chromatin: Epigenetics Goes Open Access


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While Landes Bioscience made headway by debuting a journal devoted solely to epigenetics (Epigenetics), BMC has really opened the door to epigenetics research by debuting the first open-access journal devoted to epigenetics. Epigenetics & Chromatin is a new open-access option for researchers wanting to make their research available to a wider audience. The co-editors, Steven Henikoff and Frank Grosveld, are open to a wide range of topic areas:

Epigenetics & Chromatin will publish articles aimed at understanding how gene and chromosomal elements are regulated and their activities maintained during cell division, self-renewal, differentiation and environmental alteration. Epigenetic research encompasses studies that use model systems to discover and investigate epigenetic mechanisms, as well as studies aimed at combating diseases that involve epigenetic processes. Topics include, but are not limited to, gene activation, silencing and imprinting, cellular reprogramming, nucleosome modification, assembly and remodeling, DNA methylation, chromatin structure and dynamics, chromosomal maintenance elements, dosage compensation, intra- and inter-chromosomal interactions and prion inheritance. Approaches that apply cutting-edge technologies to problems in the field are especially welcome.>

A publication fee of US$1800 is pretty standard fare for an open-access journal, and I’ve heard that many scientists are willing to pay the fee if it means increased awareness (and citations) of their work. I have to believe that with an increased focus on the field from a diverse arrange of disciplines, Epigenetics & Chromatin will be a popular and high impact journal. Link

Constellation Pharmaceuticals Aims to Develop Epigenetic Drugs


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One of the news items that was missed in April during the brief hiatus was about a new biotech outfit (Constellation Pharmaceuticals) that had raised $32 million in a series A round of funding. The company immediately drew my attention not because they were planning to develop epigenetic drug therapies for cancer, but because of their founders: David Allis, Yang Shi, and Danny Reinberg are all well-respected scientists in the epigenetics field, and their founding of the company brings an immediate legitimacy to the organization, which was no doubt helpful in the round of funding. Additionally, it probably didn’t hurt gaining the attention of Mark Levin of Third Rock Ventures, the former cofounder of Millenium Pharmaceuticals, who is now the interim CEO of Constellation.

The young company’s web site is full of promising publicity talk about the potential of epigenetic therapies, but little of material value. However, the company is quite young and it will likely take awhile before any promising candidates emerge. As a side note, if you’re a BS/MS-level graduate in molecular biology looking for work, Constellation is hiring in the Boston area.

For more information about Constellation, see this article from the Boston Globe.

Getting a Research Associate Position


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I was able to secure an offer for continued employment as a Research Associate at Washington State University. I will be working in the lab of Dr. Skinner, who many know that I had also been working with during my undergraduate years. He has several NIH grants and recently secured new funding from the Department of Defense for a project that I will be closely involved in.

The job hunting was exciting early on, but quickly moved into the frustrating stage and finally the depressing stage. The fact is there are a lot of unemployed M.S. and PhD scientists around here, and they are all in need of income, which means that they had been forced to settle for research technician jobs that are normally taken by B.S. graduates like myself. My 5+ years of research experience had a favorable impact on getting into final candidate lists, but I was only able to secure two offers from a list of 8 or 9 jobs. The rest were largely taken by those with advanced degrees. I was fortunate to have an hourly position to keep the bills paid during the process, which I know from experience could have been far more than depressing.

In the lab, my “unnamed” project, which I have been working on since 2005, should be coming to the point of publication soon. For the longtime readers this is something they have probably heard before, and I should have learned my lesson long ago and just not make any predictions about it. Nonetheless, all the added data accrued during this time has been extremely productive, and should make for an interesting paper when it finally gets to that point.

As for my writing here, as you can see it hasn’t been consistent. Our family was able to take a couple trips over the summer, including one a week ago to the Newport, Oregon area, which is a spot my family regularly went to growing up. It was good to share that experience with my wife and stepson.

Hopefully now that the summer is coming to a close (classes start today here at WSU) the blog updates will be more consistent and often.

Intro to Epigenetics


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University of Minnesota-Morris biologist PZ Myers has written an introduction to epigenetics at Pharyngula, with some nice illustrations of some of the basic concepts and mechanisms that are generally grouped under the heading of “epigenetics.” It’s a great way to bring yourself up to speed if you don’t know much about epigenetics and want a single article to give you the basics. I’ve come to realize that the majority of the readers here are not in that crowd, as many are working in research labs and companies that have some connection to the area of epigenetics and want to keep up on the very latest developments in epigenetics. So for those are you that are not part of that group, I highly recommend that you head over to this article and read about the basics of epigenetics. Link

One of the questions brought up in the article, which has been covered here before, is what all falls under the umbrella of epigenetics? I think that this is largely an issue of semantics, with some established researchers having an interest in restricting the use of the word in literature, and many others expanding the reach of the word to greater and greater lengths. As I’ve mentioned before, I think this trend is largely a result of the funding opportunities available, and the general trend in recent years as epigenetics becoming one of the “hot new” areas of science.

Merging Blogging with the Pursuit of Academic Tenure


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John Hawks, who has maintained a popular blog focused on his field of expertise in paleoanthropology, has begun a series of posts discussing some of the pros and cons of blogging during the early years of a tenure-track position, and how he was able to successfully integrate his blogging activity into his tenure application (Hawks was granted tenure last month). The first segment (How to blog, get tenure and prosper: Starting the blog) is both insightful and honest, which is just the sort of writing I’ve come to expect from John Hawks.

A Professor and a Graduate Student Mull Over Epigenetics


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PZ Myers (Pharyngula), an associate professor in developmental biology, and Abigail Smith (erv), a graduate student studying retoroviral evolution, talk about a number of topics in a bloggingheads.tv exchange, including epigenetics. The segment of the video discussing epigenetics is embedded below.

NanoDrop It Like Its Hot


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I just came across this video on the NanoDrop Technologies web site. The NanoDrop is a new spectrophotometer that is growing popular among molecular biology researchers due to its ease of use and time effective advantages over traditional spectrophotometers. I’ve been using it exclusively for getting DNA and RNA concentrations; the results have been great and much more reproducible than some of the old spectrophotometers around here. I think the video was well done by the students from Brown University.

My only question: If these students had time to shoot and edit this video, how did they also have time to put together enough research for two Nature publications?

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Epigenetic Abnormalities in Animal Clones Downplayed in Report on Food Safety from FDA


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The Washington Post is reporting this week on a 968-page report from the U.S. Food and Drug Administration (FDA) on the safety of food from cloned animals that are now widely available.

A long-awaited final report from the Food and Drug Administration concludes that foods from healthy cloned animals and their offspring are as safe as those from ordinary animals, effectively removing the last U.S. regulatory barrier to the marketing of meat and milk from cloned cattle, pigs and goats.

The article from Washington Post staff writer Rick Weiss highlights one of the anomalies that FDA scientists acknowledge in cloned animals but have chosen to discount: their epigenetic abnormalities. Indeed, researchers are only beginning to unravel the role that epigenetics plays in the long-term health and viability of cloned organisms. Yet, the FDA doesn’t see this as a problem:

Finally, there was the overarching problem of deciding which measures would best predict whether the food was safe. Most puzzling was whether to take into account the subtle alterations in gene activity, called epigenetic changes, that are common in clones as a result of having just one parent.

In the end, facing the reality that epigenetics have never been a factor in assessing the wholesomeness of food, agency scientists decided to use the same simple but effective standard used by farmers since the dawn of agriculture: If a farm animal appears in all respects to be healthy, then presume that food from that animal is safe to eat.

While this seems to be a “no nonsense” approach to take in considering the potential impact of epigenetic changes in considerations of food safety, in some ways it wholly discounts the concerns that researchers have about epigenetic alterations in cloned animals.

In the report, the FDA promises a number of key areas that it will continue to survey going forward as cloning technologies and additional research becomes available, including new insight into the “biology of epigenetic mechanisms governing gene expression.”

What do you think about eating meat and milk from cloned animals? Link

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Science Links for December 8, 2007


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  • One of the postdocs here in the Skinner lab, Dr. Ramji Bhandari, has started a blog related to his area of expertise, Sex Determination Research. Ramji is new to blogging and decided to get his feet wet with a number of relevent abstracts, which will be a nice resource for those interested in sex determination.
  • Cautious forays into open science continue. Dr. Rosie Redfield of the University of British Columbia is a vocal supporter, and recently explained her philosophy in blogging about her current experiments and encouraging her lab members to do the same.
  • Also, Pedro Beltrao is testing the use of Google Code as a management system for conducting an open science experiment involving domain family expansion.

  • The Pump Handle, a blog that provides editorials and commentary on emerging trends and issues in public health, has started a new feature, Journal Scan, that provides explanations of research papers in easily understandable language. Anyone with an interest in public health can break down a paper and send it in for publication.
  • Seattle’s Fred Hutchinson Cancer Research Center is home to Steve Henikoff, who is profiled in the Proceedings of the National Academy of Sciences. Dr. Henikoff is a Howard Hughes investigator and a leader in epigenetics research. The profile exmaines his entire life, from growing up in Chicago to developing (with wife Jorja) the BLOSUM protein alignment scoring matrix, while in the process delving into some of the science that Henikoff has helped push forward over the course of his career.

Review Highlights Recent Advances in Computational Epigenetics


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A nice review article by Bock et. al. in Bioinformatics sheds light on some of the recent advances (2006-2007) being made in computational epigenetics. Some highlights:

  • The article provides a succinct introduction to epigenetics research for bioinformaticians that are new to the field, including explanations of mitotic vs. meiotic epigenetic inheritance, mechanisms of epigenetic regulation, and common techniques for genome-wide mapping of the epigenome.
  • CHIP-on-chip analysis is explored from a bioinformatics perspective, providing technical details on how this data can be efficiently analyzed with freely available tools.
  • The review provides a handy list of epigenome mapping projects and their current state as of October 2007.
  • The review notes some of the ways in which the ENCODE project has helped to develop more refined techniques for bioinformatics analysis of epigenetic data, such as new methods for using epigenetic information in promoter prediction.
  • One key challenge in computational epigenetics is the issue of public data storage. Hundreds of gigabytes of data can be generated routinely, and the ability to easily share the data on publicly accessible servers will be an ongoing issue.
  • Using epigenetic data for promoter prediction is increasingly becoming less relevant, therefore work is now being focus on advanced questions of transcriptional control, such as inferring tissue-specific signals and reconstructing transcriptional networks.
  • The concept of CpG islands are being refined based on new insight using genome-wide computational studies to better predict the location of CpG islands and DNA methylation.
  • Recent work in cancer epigenetics has shown the potential benefits of combining computational and experimental approaches in deciphering how epigenetics shapes cancer progression.
  • The authors expect that future computational studies in epigenetics will increasingly take into account the proteins that read and write epigenetic information, and that reduced costs in epigenome mapping will enable many studies of epigenetic variation in human populations.

And finally: “In conclusion, exciting times are ahead for research in computational epigenetics!”

References:

Bock C, Lengauer T. 2007. Bioinformatics Advance Access published online on November 17, 2007.

doi:10.1093/bioinformatics/btm546

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Backing up Research Data and Publications with Mozy


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I’m a regular reader of Derek Lowe’s In the Pipeline, an excellent blog written by an industry chemist that offers insight on careers in research, the ups and downs of life in the lab, and his unique perspective on pharmaceutical news. His recent post about the lengths that he went through to back up his dissertation during grad school was something many people can identify with in terms of the importance of some documents — whether it be research data or priceless digital photos of birthday parties and vacations.

Mozy 1

Mozy is a simple solution that I use to back up important files. Available for Windows 2000, XP, and Vista, and Mac OS X 10.4, Mozy automatically backs up files that you specify to a secure server. The great part is that Mozy works without assistance — you don’t have to remember to start the backup every so often. Mozy can be set to backup at certain times (such as the middle of the night), or when your computer has been idle for 30 minutes, for example.

Mozy 2

Mozy also has a convenient feature that allows you to backup common types of files, such as your iPhoto or iTunes library, Excel or PowerPoint documents, or application preferences. Other files and folders can also be selected manually.

The best part is that Mozy is completely free for up to 2 GB of files. Unlimited backup space is available for $4.95 per month. Use this link to get an additional 256 MB of free backup space.

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Bringing Your Research Lab’s Web Site into the 21st Century


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I have been asked by enough people for advice on making their lab web site “better” for various reasons, so I decided to put together a list of things that will have a tremendous impact on a researcher’s ability to provide readers with the information they’re looking for, convey a professional effort in its appearance, and keep journalists, students, and others coming back regularly for updates. With that said, here are my top 5 tips for bringing your research lab’s web site into the 21st century:

1. Offer RSS feeds for your own papers or papers within your specific speciality. An RSS feed is a simple and effective way for anyone to keep updated with your work without constantly checking your web site. They are easily set up and maintained, and can be added to any type of web site, including your lab’s home on the web.

2. Make an XML sitemap and submit it to Google. If you don’t want your research (probably publicly funded) to be widely disseminated, why are you doing it in the first place? One of the best ways to help people find your site is to get it in the search engines. The best way to do that? Make an XML sitemap and submit it Google using their handy webmaster tools. They’ll then know where each of your site’s pages are, and will check them regularly for updates. That means your pages will appear more quickly in search results, meaning your research will be easily found, and more likely to be cited in other papers. See XML-Sitemaps.com for more information.

3. Provide PDF reprints of your latest papers. Let’s face it: not everyone has the luxury of an institutional subscription for access to hundreds of journals. Why not offer simple PDF reprints of your latest papers right from your site? This not only makes your work more widely available (and more likely to be cited), it also makes it dead simple for prospective graduate students, for instance, to see what you’re actually working on right now. (Of course, this tip would be negated if all of your work was available in open access journals, but that’s not very likely.)

4. Update the site regularly. This tip may seem simple, but most researchers are “too busy” to follow it. How many lab web sites have you been to with the latest paper shown is 2 or 3 years old, yet they have 10-15 papers published over the last couple years? I’ve seen dozens of sites just like this, and I’m hoping it’s not yours. Just taking the time and effort to keep your site reflective of your lab’s current work is a step in the right direction.

5. Take the web site seriously. A large majority of the lab web sites that I have seen in recent years are absolute jokes in terms of their utility. Students, journalists, fellow researchers — they would all be equally dissatisfied with the experience. We’re talking about the way in which hundreds of thousands of people will be able to judge your life’s work, and you put up a simple page with a generic research outline (probably outdated based on your current work) and a CV and call it good? This is not good enough for today’s researchers. In fact, it wasn’t good enough five years ago either.I have heard grumblings from some professors that go something like, “I’m too busy to constantly update my web site,” or “I don’t know enough about that technical stuff to do it right.” I’m sorry, but these excuses just don’t float when a simple job like this can be contracted for $500 or less — an amount you probably spend on pipette tips in a month. Remember, this is your contact point for telling the world about your life’s work. Isn’t that important enough to make a solid effort?Now maybe if you do your web site well enough, and people can clearly understand the relevance and importance of your work, you will also be nominated for 2007 Time Person of the Year, just like epigenetics and imprinting researcher Dr. Randy Jirtle was. (See Dr. Jirtle’s site, Geneimprint.org, for a site done right.)

McGill University Exploring Link Between Childhood Abuse and Adult Suicide


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Canadian weekly magazine Maclean’s has published a brief article profiling the ongoing work of Dr. Moshe Szyf of McGill University, who for years has been at the forefront of cancer and nutritional epigenetics. Dr. Szyf is currently collaborating with McGill neuroscientist Dr. Gustavo Terecki, director of the McGill Group for Suicide Studies. A brief synopsis and early results from the study:

The brains of eight men who had died were analyzed. Their medical records showed that each of them had experienced childhood abuse — physical, sexual or mental, or a combination of the three. All had committed suicide in their mid-thirties. The chemical marking on their brain DNA was compared to that of people who had non-abusive childhoods and died of natural causes.The results will likely be published later this year, but Maclean’s was given an early synopsis. The gene regulating stress was less active in the eight men. Szyf and Turecki both speculate this left the men hard-wired to have problems coping, which may have contributed to their suicides. 

Dr. Moshe Szyf was also founder of biopharmaceutical company MethylGene, Inc., and was the founding editor of the Landes Bioscience journal Epigenetics. Link