Larry Marnett. Ph.D. Dean Dixon
Marnett gives progress report on first year of institute
One month past the first-year mark of directing the Vanderbilt Institute of Chemical Biology, Larry Marnett, Ph.D., wears a smile when he talks about its progress.
He has reason to feel satisfied. Faculty recruitments have exceeded expectations, core facilities are expanding to accommodate supporting technologies, a new group of fellowship-supported students has begun classes, and a weekly interdisciplinary seminar series is building community.
“It’s been a good year,” he said. “We’ve put a lot of resources and tools in place, and it’s becoming a really big program. I want to thank everybody who has given us such terrific support and cooperation in our first year, beginning with Chancellor Gee and the opportunities that the Academic Venture Capital Fund has afforded us.”
The Vanderbilt Institute of Chemical Biology (VICB) is one of six initiatives funded by the AVCF, an internal grant program designed to boost areas of trans-institutional research judged by campus leaders to have the potential to evolve into programs of national stature.
“We adhered pretty closely to the plans we laid out a year ago, and I think we’ve used the resources the university gave us as wisely as we could,” said Marnett, Mary Geddes Stahlman Professor of Cancer Research, professor of Biochemistry and Chemistry, and director of the A.B. Hancock Jr. Memorial Laboratory for Cancer Research.
A joint enterprise between the School of Medicine and the College of Arts and Science, the VICB’s mission is to promote research and education in the application of chemistry to biological problems. Now that the human genome has been sequenced, Marnett says, this approach becomes essential as the focus of attention shifts from what the players in the cell are to how they work.
“You’re talking about structure, function, analysis — these are the tools of chemistry,” he said. “We are heading into an era where chemistry will be a dominant player in the way that people ask biological questions. We feel that the VICB is perfectly positioned to build the strengths that Vanderbilt needs to be a major player in the post-genomic world.”
Recruiting strength
To bolster those strengths, five new faculty members were recruited by the VICB over the past year. Two of them — Darryl Bornhop, Ph.D., and Brian O. Bachmann, Ph.D. — joined the department of Chemistry on the Arts and Science campus.
Already a collaborator with a number of Vanderbilt researchers before his arrival, Bornhop, professor of Chemistry, is focused on the synthesis of imaging agents for use in both molecular and functional imaging. Clinical trials are in the works to evaluate the use of his synthetic molecules in imaging tumors. Bachmann, assistant professor of Chemistry, uses molecular biology techniques to re-engineer genes that make naturally occurring antibiotics.
“It’s a way to expand antibiotic diversity biosynthetically rather than chemically,” said Marnett.
New faculty members on the Medical Center campus have all been joint recruitments with other centers and departments.
H. Alex Brown, Ph.D., Ingram Associate Professor of Cancer Research and associate professor of Pharmacology, is well known for developing a powerful method for high-throughput determination of the changes in phospholipids that occur at the cell membrane following initiation of cell signaling.
Daniel C. Liebler, Ph.D., professor of Biochemistry and Director of Proteomics, is an expert in high-throughput identification of proteins and how they are biologically modified, for example, as a result of toxicity or through signaling pathways.
The third Medical Center faculty member is P. Jeffrey Conn, Ph.D., professor of Pharmacology and Director of the Program in Translational Neuropharmacology.
Conn, who earned his doctoral degree in Vanderbilt’s Pharmacology department, was recruited from the pharmaceutical company Merck & Co., Inc., where he headed the neuroscience research program.
Expanded technologies
Conn has been instrumental in helping Vanderbilt develop the capability for high-throughput screening of small molecules that have potential for use as therapeutic agents, according to Marnett.
“We’ve merged this high-throughput screening activity with the screening that goes on in what was the Molecular Recognition core facility, run by Ray Mernaugh, Ph.D., and administered through the Cancer Center,” he said. “Ray is now the director of the combined core, which we call Molecular Recognition and Screening.”
The VICB has invested in a large, modular robotic screening unit for the core capable of assessing 300,000 compounds in a single biological assay. The Institute plans to purchase a 100,000 compound library for use by investigators in assessing their particular biological questions.
The idea is to not only find lead molecules that drug companies might develop, but also to provide small molecule probes for use in cell-based or in vivo studies to test the involvement of a protein in a given biological response.
“The big advantage of a small molecule over a genetic knockout is that you still have the rest of the protein there,” said Marnett.
“If you knock out a gene, all the protein-protein interactions associated with that knockout are gone. But if you have a chemical agent that binds to just one site and knocks out a specific effect, other binding interactions to that protein remain intact. You also have precise control over the timing of a chemical knockout. In some ways it’s a cleaner experiment.”
Support from leadership on the two campuses and cooperation between the Center for Structural Biology and the Chemistry department have made possible development of a second resource for researchers: an analytical NMR facility.
“We haven’t had the kind of small molecule analytical NMR facility that a place like Vanderbilt should have,” said Marnett. “We’ve now got the wherewithal to assemble such a facility, and we’ve hired a new director, Donald Stec, Ph.D., to run it. The facility will be a major strength.”
A collegial atmosphere
As a trans-institutional entity, the VICB relies on cooperation among all partners for its success, and nowhere is a close working relationship more essential than between the School of Medicine and the department of Chemistry.
With the recent announcement that associate director of the VICB, Ned A. Porter, Ph.D., Stevenson Professor of Chemistry, has been named chairman of the Chemistry department, the relationship stands to grow even stronger.
“It’s very important that the Chemistry department and the Institute cooperate,” said Marnett. “Over the last five years — beginning with David Hercules’ leadership and now with Ned Porter’s leadership — there has been a growing appreciation for the opportunities that partnering with the Medical Center presents.”
The VICB contributed to the recruitment of six pre-doctoral students this year, three in the Chemistry department, two in the Chemical and Physical Biology (CPB) program, and one in the Interdisciplinary Graduate Program (IGP). Several of the students are supported by fellowships provided by the VICB.
A seminar series in chemical biology is held weekly, co-sponsored with the departments of Chemistry, Biochemistry, and Pharmacology. “We have a really outstanding program planned for this fall,” said Marnett. “We meet on Wednesdays at noon in MRBIII, which is an excellent intersection point. The talks have been very successful at bringing both sides of the campus together.”
Marnett and Porter intend to build on current momentum as the VICB moves into its second year. “The next year is a very important one for us,” he said. “We’ve made a good start. Now is the time to consolidate those gains and focus on making an impact here at Vanderbilt and around the country.
“Again, I’d like to thank all those who have supported us in our first year, especially Dr. Harry Jacobson, vice chancellor for Health Affairs, Nick Zeppos, J.D., provost and vice chancellor for Academic Affairs Lee Limbird, Ph.D., associate vice chancellor for Research; Dennis Hall, Ph.D., associate provost for Research; Dr. Steve Gabbe, dean of the School of Medicine; Richard McCarty, Ph.D., dean of the College of Arts and Science, Heidi Hamm, Ph.D., chair of Pharmacology; Mike Waterman, Ph.D., chair of Biochemistry; and David Hercules, Ph.D., chair of Chemistry.
“Special credit and thanks are also due to our terrific administrative staff. Anne Lara is the manager of the VICB, Celeste Riley is the administrative officer, and Mary Veazey is the administrative assistant. They’ve worked really hard to make all of this happen, and they’ve done a great job.”