(mentions CMT Inherited Neuropathies) The ABCs of Good Research

[Guest guest]

The ABCs of Good Research

http://www.genomeweb.com/sequencing/abcs-good-research

July/August 2009

By Dublin

With more than 20 years of experience as both a physician and a researcher,

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 called Dr. 56, 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.

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 one of the largest DNA sequencing facilities in the US.

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.

As an assistant professor in the human genetics department at Emory University,

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.

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.