Tangled Bank #52

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The 52nd edition of The Tangled Bank, a collection of links to the science blogosphere’s choice pieces over the past two weeks, is now available at The Inoculated Mind. Among the highlights is a post covering some of the genetic diagnostics tests that are available today, the tendency of people to use genetics as an excuse, and the potential future uses of science blogging. Link

Scientists in Training: The Experience Dilemma

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I happened to be browsing the science blogosphere and came across a couple of interesting commentaries from Sandra Porter at Discovering Biology in a Digital World about the lack of opportunities for high school and college students to gain real world experience in the realm of biotechnology and lab research.

While I am in strong agreement with Dr. Porter’s contention that opportunities for students to experience hands-on lab work are few and far between, I thought it would be appropriate to offer an opposing view to balance this issue – albeit from the eastern side of Washington state – from an undergraduate college student that is doing independent lab research on a daily basis. Link

    So when I started college, I started looking for jobs that would do more than pay the rent. I wanted first-hand impressions of potential careers… My medley of part-time and volunteer jobs were eye-opening forays into the working world.

I couldn’t agree more with this outlook. My return to school and my interest in pursuing a degree in Genetics and Cell Biology were instigated by a summer job with the USDA’s Agricultural Research Service, working with a wheat geneticist on developing and testing new breeds of wheat. The job itself was grueling physical work in hot and dusty conditions, but my interest in science was piqued, and I ended up returning to college as a freshman again after a seven year holdout (including stints as a writer, editor, manager – all past lives).

    The job that I wanted the most though, was the hardest to get. I really wanted to work in a science lab. Every now and then I would go to the student employment center and look at the job postings, but I was never eligible. The lab positions at my University required either work-study funding or work experience and I had neither.

This is also fairly true at Washington State University, although a number of other undergraduate students and myself have benefitted tremendously from a few principal investigators (P.I.s) that have relatively stable and abundant grant funding. These researchers tend not to worry too much about whether they will have enough money to keep the students working for another year, but rather take the annual opportunity to identify 1) students that have remained productive, and 2) students that have not.

    Even though some business leaders might recognize the long-term benefits of contributing to a scientifically literate society, and inspiring future employees, few companies want to accept the risk of having an $80,000/year employee spend the summer babysitting a student intern.

Essentially, our lab treats undergraduate students as low-cost lab technicians. With the right selection of hard working students and a little training from postdoctoral researchers, the “student researchers” become efficient technicians without all of the hassle of a pay commensurate with a bachelor’s or master’s degree or the added cost of benefits. While work-study funding is especially enticing for the P.I., it isn’t absolutely necessary given the obvious benefits of adding productive workers at a lower cost.

    We still have the same catch 22 that I experienced in college. Biotech companies and University research labs want to hire experienced people, but they’re unwilling or unable to provide that experience. Students need experience to get jobs, but they can’t get jobs without experience.

Apparently, the lab that I work in does not fall into this category. The majority of the students that work in our lab have no experience in a research lab prior to being hired, yet are often completing assays independently within a few months of hire.

And with these opportunities to work directly in a university research lab, students become more aware, for better or worse, what doing lab research really entails. The work ends up enticing some students to the research path and sending others running away from it.

The second part of the series by Dr. Porter lists several intriguing options for “scientists in training” to gain hands-on experience in the lab, including hands-on programs from technical colleges and collaborations between community college programs and private biotechnology companies. Link

QIAGEN Offers Kit for Epigenetics Researchers

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QIAGEN has introduced a new kit that offers a complete solution for bisulfite conversion of DNA. The assay is routinely used in epigenetics research because the labelling process discriminates between cytosines that are methylated and those that are unmethylated. The new kit promises “high yields of completely converted, high-molecular-weight DNA…in less than six hours.” Link

Methylation “suburbs” implicated in colorectal cancer

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Nature Genetics has published ahead of print a research article providing new insight into the role that epigenetics plays in the aetiology of colorectal cancer. A research group led by Dr. Susan J. Clark of Garvan Institute of Medical Research in Australia have correlated the global gene suppression of chromosome 2q.14.2, spanning four Mb, in humans with methylation of CpG island “suburbs.”

    DNA hypermethylation within the repressed genomic neighborhood was localized to three separate enriched CpG island ’suburbs’, with the largest hypermethylated suburb spanning 1 Mb. These data change our understanding of epigenetic gene silencing in cancer cells: namely, epigenetic silencing can span large regions of the chromosome, and both DNA-methylated and neighboring unmethylated genes can be coordinately suppressed by global changes in histone modification. We propose that loss of gene expression can occur through long-range epigenetic silencing, with similar implications as loss of heterozygosity in cancer.

The authors have also proposed, in connection with their research findings, that the term “suburbs” be used to describe the chromosome “neighborhood” that is implicated in an epigenetic mechanism; that is, a chromosome neighborhood can be divided into a suburb with methylated DNA and a suburb with unmethylated DNA.

This research is important because it potentially means that increased DNA methylation in much larger areas than previously thought could be important in the mechanism leading to the development of colorectal cancer, and potentially other cancers as well. Link

The History of Epigenetics Explored

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The second issue of the Journal of Epigenetics is now (partially) available online, with free online access to this new journal through the end of 2006. The issue contains an informative historical overview of the field of epigenetics, beginning with the coinage of the term “epigenetics” by Conrad Waddington to help merge the fields of developmental biology and genetics.

Building on the work of Waddington and others, the article delves further into the efforts made by scientists over the last thirty years to explain how some differentiated cell types, such as fibroblasts and lymphocytes, “stably maintain their phenotype through cell division.” The notion that the methylation of DNA could affect gene expression, and that these methylation patterns could be heritable, was proposed independently by two groups in 1975. That same year, other papers were published exploring the possibilities that eukaryotic organisms contained enzymes that restrict unmodified DNA, and that methylation patterns in cancer cells could affect gene expression. Interestingly, none of the papers used the word “epigenetics.”

Author Robin Holliday also uses this publication to review the two definitions for epigenetics that were proposed in 1994, along with the role that his own 1987 paper, “The inheritance of epigenetic defects,” played in increasing the use of the word “epigenetics” throughout the 1990’s.

Other important topics discussed in this paper are the key differences between genetic and epigenetic mechanisms, the potential role and evidence for chromatin configuration affecting epigenetic inheritance, and the importance of clearly defined terminology, such as “epigenotypes,” as The Human Epigenome Project attempts to get underway. Link

Tangled Bank Offers Latest Science Writing

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Tangled Bank is a collection of writing from the past two weeks covering the most interesting and thought-provoking science writing around the Web. The 51st edition of Tangled Bank is now available at Discovering Biology in a Digital World.

The collection includes a number of links that may be of interest to Epigenetics News readers, including David Haussler’s work on the reconstruction of ancient genomes, Google’s threat to genetic privacy, and a summary of some of what is now known about the genetics of cancer. Link

Protein Plays Role in Hemoglobin Gene Silencing

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Researchers at the Virginia Commonwealth University Massey Cancer Center have identiifed the role of a protein, MBD2, that mediates silencing of the fetal gamma-globin gene through DNA methylation, an epigenetic mechanism.

The study employed a transgenic mouse model containing the human hemoglobin gene locus to show that MBD2 interprets the DNA methylation “signal” throughout the genome, which determined how the pattern of methylation affected the expression of specific genes.

Previous clinical studies have shown that patients with sickle-cell anemia or beta-thalassemia see a positive effect when gamma-globin gene expression is increased.

“The gamma-globin genes normally become silent in adult hemoglobin expressing red blood cells. If we can find a specific and safe mechanism to reactivate the gamma-globin gene, we may be able to overcome the underlying molecular defect in sickle-cell anemia and beta-thalassemia,” said lead author Gordon D. Ginder, M.D. Link

Biotech’s Most Important Ethical Concerns

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There is an interesting post from Sandra Porter at Discovering Biology in a Digital World about the disparity between the top “ethical issues” cited by biotechnology companies today, and the topics that are routinely covered in bioethics courses at colleges around the country. Link

Why Epigenetics News?

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From the moment that I let slip to other members of the lab that I had started a blog about epigenetics, the inevitable questions were, “Why? What’s the point? Who’s going to read it?”

Well, I’m going to answer those questions for everyone to read.

While I’ve only really been involved in research for a few years now, it has been my experience that there exists a lack of fundamental knowledge on the part of the “lab staff” on not only the concepts and rationales for their own area of investigation, but also they are not familiar with recent advances made in their field for months, if not years after they are published.

I formerly worked as a news editor and writer, and with me being accustomed to keeping on top of everything new in my field, I found this trend to be baffling. The information was clearly out there, but why weren’t they reading it?

Well, perhaps they just don’t care. After all, it’s essentially their job to do what they’re told to do by the principal investigator. Maybe they’re just there to come in to work, run their assays, and go home with their paycheck. Thank you very much.

But maybe they really are interested in knowing more about what’s going on in their field of research, but it’s just too difficult to keep on top of everything. It takes too much time, and that’s time that could be used to set up another PCR.

So, that was my initial rational for creating Epigenetics News. It has since become clear that many others are also intrigued by the field of epigenetics, and so perhaps this will be a helpful resource for many others to explore the world of methylation.

Science Writing Contest from Seed

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Seed Magazine is hosting a Science Writing Contest, open to U.S. residents, that calls for an essay of no more than 2,000 words on the following topic:

    Amidst emerging competitive threats from abroad (China and India in particular) and heated debates over intelligent design, stem cells and climate change: What is the future of science in America? What should the US do to preserve and build upon its role as a leader in scientific innovation?

The first place entry will have his/her essay published in the magazine and receive $1,000. Second and third place will receive $500 and $250, respectively, with their essays published on the magazine’s Web site. Entries must be submitted by June 30, 2006. Link

Predicting Recurrence of Prostate Cancer

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A new study shows that a test checking for hypermethylation of a single gene can predict recurrence of prostate cancer in patients who have had their glands surgically removed. Epigenomics AG announced today that in a clinical study of 605 prostate cancer patients, those patients who tested positive for hypermethylation of the PITX2 gene were three times more likely to experience cancer recurrence than those who tested negative. The test was also accurate in predicting recurrence for all patient sub-groups, including patients with organ-confined and non-organ-confined disease.

The study was also examining five other genes where hypermethylation was correlated with cancer recurrence, but the researchers found that testing methylation of the PIXT2 gene alone could be used to develop a score that defined a good prognosis group (with 94 percent PSA-free survival 10 years after surgery) and a poor prognosis group (with 70 percent survival).

While the current test used prostatectomy samples, the next goal of the researchers is to see whether the same results can be obtained by testing prostate biopsies. Link

Methylation marker for colorectal cancer detection

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New data shows that colorectal cancer can be detected early by a free-floating blood test looking for a methylated version of the septin 9 gene. Molecular genomics company Epigonomics AG announced that it has completed a set of studies showing that “presence of the methylated form of DNA encoding the so-called Septin 9 gene is found in plasma of up to 57 percent of patients with all stages of colorectal cancer at high levels of specificity (95%).” The key advance of the screening tool is the ability for patients to screen for colorectal cancer with a blood test rather than with the conventional test requiring submittal of a fecal sample. Link

Thanks for checking us out

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I would like to thank Razib and the readers of his great blog Gene Expression for checking out this very new blog offering news and information in the field of epigenetics. Please keep an eye out in the upcoming weeks as additional information and resources on epigenetics is being developed.

Update: Also thank you to Hsien at Genetics and Health for the mention.

Epigenomics Seeking Scientist in Seattle

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Germany-based Epigenomics AG, which is at the forefront of developing assays for studying and diagnosing the link between epigenetic factors and disease, is looking for a qualified scientist for clinical assay development in its screening group in Seattle, WA.