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The ABCs of Good Research

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With more than 20 years of experience as both a physician and a researcher, Eric Green has been in the trenches of genomics research virtually since the beginning. Given his wide range of expertise and breadth of experience, it should come as no surprise that Green holds more positions than your average PI. In addition to serving as the scientific director of the National Human Genome Research Institute, Green is also chief and senior investigator of the Genome Technology Branch, head of the Physical Mapping Section, and director of NIH's Intramural Sequencing Center.

While he's juggling all of those responsibilities, he manages to pursue a range of research projects that fall under the rubric of genome sequencing, including sequence analysis, comparative genomics, population genomics, evolution studies, medical sequencing, and microbiome studies. Green is helping to lead NISC's ClinSeq project, an interdisciplinary study that aims to evaluate the use of large-scale medical sequencing in the clinic. In another clinically oriented project, Green and NISC are looking at microbial communities living in and on the human body through large-scale meta-genomic sequence analysis.

Green, a graduate of the Medical Scientist Training Program at Washington University in St. Louis, is that rare kind of researcher who also trained as a physician. While this was no easy path to embark upon, Green believes that the combined training is great and exposed him to the full spectrum of basic research and clinical medicine. "While I do not practice medicine any longer, there is no question that my medical training has served me well throughout my professional career — in particular, as I have assumed leadership positions at NIH," he says. "Being trained as a physician-scientist is certainly valuable for pursuing some of the most exciting projects in genomics today."

Communicate and connect

Despite the scope of his activities as a leading investigator, Green is more than willing to put everything he has into mentoring up-and-coming researchers to help them reach their full potential. Usually this is not so much a matter of guiding the direction of their research projects, but rather, making sure brilliant scientific minds are as adept at communicating with the larger research community as they are at analyzing sequencing data. "One of the big things I push very heavily is getting them to work very hard on their written communication and their oral communication," Green says. "So I am overwhelmingly compulsive when I co-write a paper with a trainee and I am also compulsive when they prepare talks to give. … You can be the most brilliant scientist, but if you don't write well and speak well you will not be as successful."

His approach is to have trainees draft papers to the best of their ability, but warns them to expect whatever they do to be taken apart and rebuilt anew. "We write together in a very interactive process, or if they put a talk together, they try to give it — but then I rip it to shreds in a very kind way but just to show them how much more logical it is if you do it another way," he says. "Inevitably, they come back and say, 'Oh my gosh, I see how much clearer you can state it' — and that's the teachable moment."

Another key skill Green wants to imprint on his postdocs is that the best thing they can do for their research is to get out of the lab and connect with other researchers. Interaction and collaboration are key for any career, and in an environment like NIH, there is plenty of gray matter to take advantage of. "The key thing that is so effectively done here in the NIH intramural program is the idea that the boundaries of your training experience do not stop at the walls of the mentor's laboratory," Green says. "At a place like NIH where we have such depth and breadth of scientific expertise, I strongly encourage my trainees to get out of my lab and talk to other scientists here when they have good ideas and develop collaborations and interact because there's so much expertise to tap into that I don't even dare to pretend to have."

This collaborative environment extends to publishing papers as well, and Green says it's the job of the trainees, not the mentors, to bring it all together. "Every one of the papers that we publish with the trainees involves multiple investigators, my lab just being one of them," he says. "It's the trainees that are the glue that bring these collaborations together … because they're energetic and they have time."

Green says that this was the exact same approach he experienced during his own postdoc years in Maynard Olson's lab at the University of Washington. "When I was in Maynard's lab I was highly collaborative," he says. "We had some cool new technologies and he said, 'Get out and take these technologies for a test-drive with some of these collaborators' and it wasn't Maynard setting up the meetings, it was the postdocs."

Olson's belief that outstanding trainees will do outstanding things without having to be hovered over is the same approach Green takes with his postdocs today. "It's very much a hands-off approach where you're not in their face every day pummeling them for progress, but rather you're there anytime that you're needed in person or by e-mail or whatever," he says. "It's absolutely an open door policy of just come find me — if you want to set up regular meetings, that's great, and if you want to just do it sporadically, that's great, too," he adds.

When it comes to sending his students out into world, Green says it's not only with an appreciation for collaboration, but the fruits of their research labors that are essential. "For training postdocs, a key part of what you're doing as a mentor is carving out a key area of research that that postdoc should then take with them to launch their own career," he says. "What I've attempted to do with my trainees is have them take their projects with them and use the activities in my lab as a launching pad to develop their own program."


Naming Names

Here are just a few scientists who passed through Green's lab on their way to promising careers.

Anthony Antonellis
Since completing his postdoc in 2008, Antonellis has become an assistant professor of human genetics and neurology at the University of Michigan.

He is currently focused on characterizing genetic loci responsible for inherited peripheral neuropathies in order to better understand the function of neurons and glial cells.

Gerard Bouffard
Bouffard now directs the bioinformatics group at NHGRI, where he manages data analysis for a significant DNA sequencing facility.

Rachel Ellsworth
During her postdoc with Green, Ellsworth helped identify a gene for Charcot-Marie-Tooth disease as well as regulatory elements for the cystic fibrosis transmembrane conductance regulator gene. She currently heads up the genetic studies group at the Windber Research Institute, where she focuses on identifying chromosomal regions critical to the development, progression, and metastasis of primary breast tumors.

Elliot Margulies
After completing his postdoc with Green, Margulies decided not to stray far. He is currently an investigator in the Genomics Informatics Section at NHGRI, where he develops bio-informatics approaches for characterizing genomes with next-gen DNA sequencing data.

James Thomas
As an assistant professor in the human genetics department at Emory University, Thomas has taken the skills he learned in Green's lab to investigate a range of projects including the evaluation of a potential new mouse model of Lesch-Nyhan disease, and comparative mapping and sequencing in nonhuman primates.

Jeffrey Touchman
This former Green postdoc now holds positions as assistant professor at Arizona State University's School of Life Sciences, where he focuses on comparative genomics, and also serves as an investigator and director of DNA sequencing at the Translational Genomics Research Institute.

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