What Comes After Genetics?

Guest post from James Todd, host of Duke's online "Office Hours" program.

Just when you thought you had a grip on genetics and genomics, there's this new thing called "epigenetics” that is becoming increasingly prominent.

One of the pioneers of this new field is Duke's Randy Jirtle. (visit his lab’s website)

Two years ago, the National Institutes of Health announced that it planned to provided $190 million in funding for epigenetics research over five years, as part of its Roadmap Epigenomics Program. Recent stories by NOVA, Time and the Washington Post have highlighted the importance of the field.

So what is epigenetics? Jirtle gives a definition in this video.

Curious to learn more? You can also watch Jirtle’s recent “Office Hours” interview.

Starvation Induced Arrest in Worms- Interview with an IGSP Fellow

Duke sophomore Ilka Felsen did not want to do summer school, but instead really wanted to put what she learned in class to practical use. "I came into the experience wondering how long does it take to answer a question in science. Like, why do we need 10 weeks to answer a question that doesn't even look that complicated?"

Ilka was one among the 15 students selected as IGSP (Institute of Genome Sciences & Policy) summer fellows. An Evolutionary Anthropology major and a Dance minor, her project involved starving 1 mm worms and seeing what happened over a ten week period.

Her research project was "The role of TGF-beta and insulin pathways in C. elegans L1 arrest and recovery." Her mentor was Dr. Ryan Baugh, Assistant Professor, Department of Biology.

"In simple terms, our research involved looking at C.elegans (nematodes/worms).

We wanted to explore the worms' response to starvation, and control the nutritional factors within the worms to see which genes were involved in the process," explains Ilka. "We wanted to identify which pathways are involved in starvation induced arrest, and to what extent."

Nematodes go into two reversible stages like hibernation if they are starved. If you starve them at an L1 larvae stage, they stop growing and can survive just like that, with an increased resistance to stress.

But the amazing thing is that once you give them food again, they will start again from where they stopped, as if a machine was restarted. "Worms can survive by eating a hard cuticle for almost four months."

"We knew that 2 pathways are involved in starvation induced arrest- the Insulin pathway and the TGF-beta (Transforming Growth Factor-beta) pathway. The main purpose was to understand to what extent the TGF-beta pathway was involved."

"I had seven different strains of worms, where one was the wild type while six had mutations. I starved each worm and analyzed how long they could survive over time. Through a variety of experiments and Micro X-ray experiments we found the TGF-beta pathway is involved."

The interesting part is that this kind of arrest creates hope for age-stagnation in humans too.

"I now understand how research in science is conducted at a professional level. It is a lot about taking big risks, as you never know to what extent your research is going to contribute to science."

She notes that research is a lot of thinking, as one needs to correlate a lot of things and scientifically and experimentally prove every single result.

"This was a wonderful experience for me. It was great interacting with my mentor, professors and other scientists who were doing really cool research. However, from this research experience, I also learned that pottery lessons are not science! And flies are really annoying to work with!"

So what are her future plans? "I am pre-health, and I probably want to pursue physical therapy as a career. Apart from many great things I take back from this summer fellowship, I figured out a simple cardinal rule for scientific research-- there is absolutely no room for mistakes!"

Office Hours on the Web

David Goldstein of the Institute for Genome Sciences & Policy did a live one-hour web stream last week to discuss genetics, genomics, racial disparities and his latest work on Hepatitis C treatments.

He's an interesting guy, written up last year in a New York Times article which pointed out that he “does not shy away from unpopular positions or research.” He's also the author of a 2008 book Jacob’s Legacy: A Genetic View of Jewish History which describes the use of genetic tools to examine Jewish history and culture.

This is a new thing we're trying, called Online Office Hours, and it really turned into an interesting discussion.

You can watch it here:

Hardware or Software?

Never mind nature versus nurture, the real question we should be asking about human origins is "hardware or software?" argues Duke biologist Greg Wray.

Wray gave a pizza lunch seminar at Sigma Xi's headquarters in the research triangle on Wednesday to share his view that biology's fixation on the "hardware," the coding sequences of DNA that carry blueprints for specific proteins, has obscured the more interesting story, the regulatory sequences, or "software" that tell those coding sequences when, where and how to take action.

"The diversity of life is magical. It's wonderful. It's why I'm a biologist," Wray said. "But we don't really know how it came about."

Recent science on these regulatory regions of the genome is revealing two things: 1. a bewildering complexity of genetic regulators and on-off switches that we never new existed, and 2. quite a bit of evidence that selection acts more strongly on regulatory sequences than on coding sequences.

"The regulatory regions are the fine-tuning dials of evolution," Wray said.

The most obvious example of this is staring us in the face, Wray said. The DNA of humans and chimpanzees is only about 1 - 2 percent different. Granted, 2 percent of 3 billion letters of code can be a lot of information, but aren't the differences between our species more profound than 2 percent?

Wray's cart-tipping act is making some fun waves in the science community. (see Science Magazine, Aug. 8, 2008). And, fresh off the triumphant publication of the complete sea urchin genome (no, really!), watch for Wray soon in landmark papers about malaria resistance and the size of the human brain.

Genome Boy in NYT

Duke assistant professor Misha Angrist, aka the blogger Genome Boy, does a star turn in the New York Times today. (That's him surrendering a chunk of flesh for science, at left)

It's a story about the personal genome project, in which Angrist has been a willing participant. His genome and lots of other salient details about him will be published today for everyone to read.

What will his genome say about him ... and about us?

Angrist and nine other pioneering participants in the project are surrendering some of their privacy to get the ball rolling on what PGP leaders hope will be the complete analysis of more than 100,000 individuals. (You can sign up too.)

Only then, when we've seen the commonalities and the differences and subjected them to statistical analysis, will we truly begin to approach predictive, personalized medicine. Or maybe not. We won't know until we've tried it. Thanks for stepping up, Misha.

The Stuff After Genes

Have a look at a very nicely done article on epigenetics in a thoughtful new magazine called Miller-McCune.

This is one of the better pieces you'll see on the complex interplay between environmental factors and genes. It turns out that you are what you eat. But you're also what your grandma ate. Scary to think about.

Duke's own Randy Jirtle is mentioned, as no article on the field would be complete without him. Dean Bill Chameides has blogged on Jirtle as well.

Sifting the Shifting Sands

Remember all the hullabaloo when the Human Genome was first completed in 2000? It wasn't the first genome by any stretch, and it certainly won't be the last. Science marches on!

Today, there are more than a thousand completed genomes on record -- from the classic models, nematode C. elegans, fruitfly D. melanogaster and mouse M. musculus -- plus a rogue's gallery of human pathogens, the sea urchin, rice and corn, a bunch of our fellow primates and on and on and on. New ones tumble in every week. It doesn't even make news anymore!

Virtually all of this data is publicly available to any researcher who needs to make a comparison, but we're talking about billions and billions and even a couple of trillions of bits of data.

There's a lot of great science waiting to happen in all this data because time and again researchers find recurring motifs in the genes of wildly divergent species, and in those motifs, clues about what genetic features matter most and what have been changed by evolution. But Where to begin? What tools to use? What does it all mean?!

Duke's Simon Gregory, an assistant professor in medical genetics, is one of the folks who added the mouse genome to the collection, and he also knows a few things about how to sift through this huge sandpile of data to find meaning.

So for the fifth year running, he and a few colleagues are putting on a workshop to help scientists tap into this immeasurably rich source of knowledge. The conference is a three-day geek-out they call the Duke Bioinformatics Workshop, or DBW, and it runs August 18-20.

Participants who think they can hang with it, and might benefit are encouraged to attend. Details here.

A Close Encounter With Epigenetics

It was a bit like watching 15-Minute Hamlet, a time-warped version of Shakespeare’s work that includes all of the well-known scenes without the detailed action.

Facing a standing-room-only crowd of students and faculty at a Jan. 15 meeting at the Duke Institute for Genome Sciences & Policy, genetics researcher Randy Jirtle (photo) covered in short order the background, current events and possible directions of epigenetics -- billed for this occasion as “The New Genetics of Biology.”

Shorn of most details, epigenetics is the study of heritable changes in gene function that occur without a change in the DNA sequence within cells. The field has emerged only in recent years, and Jirtle has proved a marquee player. (For his efforts, he was nominated by a top federal health official to be Time magazine’s 2007 Person of the Year, but lost the part to Vladimir Putin of Russia.)

In particular, Jirtle studies genetic “imprinting,” a form of gene regulation that doesn’t follow the usual genetic rules. Imprinting is proving to be important in determining whether infants exposed to certain environmental or nutritional agents in the womb or during the early postnatal period go on to become susceptible to a number of adult-onset diseases, including cancer, diabetes and asthma. His group’s website offers more.

Among their latest achievements, Jirtle and his colleagues identified 156 imprinted genes in humans -- the largest such list to date. Now the challenge is to determine what roles, if any, the genes play in disease.

Heady stuff -- and often above my head. But I got cut some slack: “This field is not for the faint of heart,” Jirtle told his audience. “It’s not easy to work in, but it’s incredibly exciting and important.”