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Moving Forward: Update on Work in the Lab

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The blog has fell silent for a number of months, mainly because my work and other endeavors has consumed all of my time. The work in the lab has taken on new dimensions, with our staff significantly expanded at the beginning of the semester. This has translated into a lot more time spent training and managing, rather than directly generating data. But I also spend a significant amount of time pushing some of my own projects forward.

On the professional development front I have been working on expanding my skill sets in statistics and programming, which mostly involves taking some courses (university, online, and books) and just putting in a lot of time getting my hands dirty with R. My work in the lab has started to shift to this area and I’ve spent many hours getting comfortable with a whole new set of tools.

One nice part with Dr. S is that even though I lack a PhD., I’m not treated any differently than those that have more degrees. So as one of the people in the lab with the most hands-on experience with a number of important protocols and experiments, it is often necessary to make recommendations and help with troubleshooting, as well as offer advice based on past experience. It’s been a nice challenge in shifting to a job that includes a lot of project management instead of primarily generating data.

Also, when I get a chance I keep up on a number of blogs in the science area, which mostly includes a lot of young PI’s, postdocs, and graduate students. It’s always interesting to hear how your experiences in science in compare with people at other universities and companies.

Recent Entries

PLoS ONE: Why I Changed My Mind

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Longtime readers may remember a couple years ago when I did a post subtly criticizing the relatively new journal PLoS ONE, saying that it was not much more than a repository for rejected papers from the more selective PLoS journals, such as PLoS Biology and PLoS Genetics.  Immediately after, I took flack some of the more senior people in the lab, saying I was probably premature to cast judgment on such a young journal.  And furthermore, some people suggested that I should keep my big mouth shut, as I was a lowly undergrad and, furthermore, this is how things work in academia.

I’m not about to take back what I wrote back then, because I think it was spot on at the time and was a reflection of what the journal’s product was at the time.  But that doesn’t mean that it necessarily holds true today.

PLoS ONE has gained remarkable popularity in such a short time because they avoid one of the major issues that costs many researchers a ton of time and, in many cases, grants: reviewer bias.  I’ve seen it many times in the short time that I’ve been a part of the lab here at WSU, and I’ve come to realize how much of an impact that it has on the ability of a researcher to get a reasonably justified and supported article published (and included with a grant submittal).

In addition, I’ve seen other researchers starting to understand the advantages of publishing in PLoS ONE, and as a result I think the article quality overall has gone up.

Last year I recommended to my lab that they take a look at the journal as a possibility for a future article submission, as it has the tremendous advantages of quick turnaround times for publication (which can be of tangible importance during close grant deadlines) and open access for wider dissemination of your work.

This comes up now as PLoS ONE last week launched a new blog, everyONE, where they’ll be highlighting articles from the journal and trying to stimulate more conversations around their core content.

And I hope they continue to grow, as it provides a nice template for future academic journals to follow their lead with a more interactive approach.

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.

Happy New Year!

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I was just reminded that I have been neglecting my duties as a blogger when I read this post from Alex Palazzo at The Daily Transcript.  Ironically, Alex does a great job reflecting why I have been neglecting those duties, concluding, “This is why I’m in science.”

My results had arrived! Before anyone was up, I looked over the list and realized what I had stumbled into. I couldn’t believe my eyes. It’s obviously the answer. Obvious. I should have gone fishing earlier. Now all that is missing is the last piece of the puzzle. That last factor that must link all the bits together.

This is why I haven’t been blogging. This is why it’s 10:01PM and I’m in the lab. This is why I’ve been totally obsessed with my work.

In short, I have also been chasing some loose ends that have had me completely mesmorized. And transitioning from undergraduate/part-time research work to full-time research work has had its share of challenges, but I feel like I am getting my feet under me and making significant contributions to not only the overall arc of the research but also to the productivity of the other lab members. This makes me very happy.

And with that, happy new year to all of the (loyal) readers!

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

Lab Atmosphere: Good, Bad, or Indifferent?

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One of the labs that I visited during my job interviews had the most amazing atmosphere of any lab that I have been in during my work thus far. Undeniably, it didn’t hurt that everything was clean and equipment was mostly boxed up, which meant there was no clutter to make the space less appealing. But the open sky windows and big glass windows didn’t hurt either, as well as the high, raised ceilings and plenty of space in between benchtops. Also, the adjacent lab was separated by an unclosed wall, which had the effect of making the space seem even larger. I was really looking forward to the chance to work there, knowing how much a working environment can affect your mood and, ultimately, productivity.

The lab that I’m in now has no windows, although I have plenty of benchtop and desk areas, and there’s very few people around to make noise or provide distraction, which can be a good or bad thing depending on how you want to to look at it. My question is: what is your lab environment like? Do you feel like it helps you be more productive, or could there definitely be some improvments that would make it much better?

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 exchange, including epigenetics. The segment of the video discussing epigenetics is embedded below.

Epigenetics News Returns

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In February 2008, I made the decision to shut down this blog in order to spend more time focusing on completing my degree and pushing my research project forward. Last month I completed my B.S. in Genetics and Cell Biology at Washington State University after an extremely stressful four years in which I tried to balance responsibilities as a full-time student, undergraduate researcher, husband, father, and blogger, among many other pursuits. This year, something had to give as my class schedule was extremely demanding and lab courses required a much larger share of my time. In addition, I had decided not to attend graduate school right away and was turning my attention to finding a research technician position in the area. That search is still ongoing, and I have applied for and interviewed with a number of research labs at WSU.

It’s amazing how quickly you learn about other research programs under way when you begin to interview for positions. Many of the PIs hiring are working on newly funded grants that have not yet been publicly disclosed, and being able to get a glimpse of the work being done in a wide range of research areas has been a great educational opportunity. I have been working on a particular project for the last 3+ years (still ongoing), and it’s easy to become so immersed in your research that you forget about what others are doing around you. The job search has been a refreshing change of pace and I am looking forward to the next stage in my research career, whatever that may be.

With that said, epigenetics research has continued to capture my attention over the past four months. This area of research has produced dramatic advances in our understanding of stem cells, cloning, cancer, development, nutrition, toxicology, and many other areas. With one educational milestone completed, it has opened up a space to continue to highlight important advances in epigenetics research at Epigenetics News. With some additional time available — and my newly acquired knowledge of important concepts and techniques critical to interpreting current research — I hope to make this project more of what I originally envisioned and present a more coherent view of the epigenetics research landscape.

Thank you to all of you who offered your encouragement and support for this project, and especially to those that stuck around as RSS or newsletter subscribers while the site displayed abstracts. Welcome back!

Histone lysine methyltransferases and demethylases in Plasmodium falciparum.

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Cui L, Fan Q, Cui L, Miao J
Int J Parasitol (Aug 2008)

Dynamic histone lysine methylation, regulated by methyltransferases and demethylases, plays fundamental roles in chromatin structure and gene expression in a wide range of eukaryotic organisms. A large number of SET-domain-containing proteins make up the histone lysine methyltransferase (HKMT) family, which catalyses the methylation of different lysine residues with relatively high substrate specificities. Another large family of Jumonji C (JmjC)-domain-containing histone lysine demethylases (JHDMs) reverses histone lysine methylation with both lysine site and methyl-state specificities. Through bioinformatic analysis, at least nine SET-domain-containing genes were found in the malaria parasite Plasmodium falciparum and its sibling species. Phylogenetic analysis separated these putative HKMTs into five subfamilies with different putative substrate specificities. Consistent with the phylogenetic subdivision, methyl marks were found on K4, K9 and K36 of histone H3 and K20 of histone H4 by site-specific methyl-lysine antibodies. In addition, most SET-domain genes and histone methyl-lysine marks displayed dynamic changes during the parasite asexual erythrocytic cycle, suggesting that they constitute an important epigenetic mechanism of gene regulation in malaria parasites. Furthermore, the malaria parasite and other apicomplexan genomes also encode JmjC-domain-containing proteins that may serve as histone lysine demethylases. Whereas prokaryotic expression of putative active domains of four P. falciparum SET proteins did not yield detectable HKMT activity towards recombinant P. falciparum histones, two protein domains expressed in vitro in a eukaryotic system showed HKMT activities towards H3 and H4, respectively. With the discovery of these Plasmodium SET- and JmjC-domain genes in the malaria parasite genomes, future efforts will be directed towards elucidation of their substrate specificities and functions in various cellular processes of the parasites.

The mechanism of myoblast deformation in response to cyclic strain – A cytomechanical study.

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Zheng L, Song J, Li Z, Fan Y, Zhao Z, Chen Y, Deng F, Hu Y
Cell Biol Int (Jul 2008)

Mechanical strain is one of the important epigenetic factors that cause deformation and differentiation of skeletal muscles. This research was designed to investigate how myoblast deformation occurs after cyclic strain loading. Myoblasts were passaged three times and harvested; various cyclic strains (2.5kPa, 5kPa and 10kPa) were then loaded using a pulsatile mechanical system. The adaptive response of the myoblasts was observed at different time points (0.5h, 1h, 6h and 12h) post-loading. At the early stage of cyclic strain loading (<1h), almost no visible morphological changes were observed in the myoblasts. The actin cytoskeleton showed a disordered arrangement and a weak fluorescence expression; there was little expression of talin. At 6h and 12h post-loading, the myoblasts changed their orientation to parallel (in the 2.5kPa and 5kPa groups) or perpendicular (in the 10kPa group) to the direction of strain. Fluorescence expression of both the actin cytoskeleton and talin was significantly increased. The results suggest that cyclic strain has at least two ways to regulate adaptation of myoblasts: (1) by directly affecting actin cytoskeleton at an early stage post-loading to cause depolymerization; and (2) by later chemical signals transmitted from the extracellular side to intracellular side to initiate repolymerization.