NIH Funds Dartmouth Study of Cellular Disease Processes

Dartmouth has received a five-year, $12.45 million National Institutes of Health (NIH) grant to establish an interdisciplinary project to explore how research into diseases such as cancer can help uncover new cellular processes, and to accelerate the translation of basic biological research into treatments.

Known as iTarget, the project will fund and provide mentoring for junior faculty who are engaged in early-stage research exploring the most basic cellular processes and how disease affects the interaction of cells and molecules.

The Center of Biomedical Research Excellence (COBRE) grant, administered by the National Institute of General Medical Sciences, supports the development of Dartmouth's iTarget project as an interdisciplinary biomedical research center with a emphasis on mentoring junior faculty research.

The iTarget institute will knit together lines of inquiry and laboratory resources from 10 departments across the faculty of Arts and Sciences, Geisel School of Medicine, and Thayer School of Engineering. In addition, the COBRE funding is available for renewal over two additional five-year periods.

The focus on an interdisciplinary approach to biomedical research and on faculty mentoring plays to Dartmouth's strengths, says Dean Madden, a Geisel professor of biochemistry and cell biology, director of the iTarget project, and principal investigator of the COBRE award.

"This community is very collaborative, very collegial, and already has low barriers to cooperation. We will be leveraging that underlying strength when pursuing this interdisciplinary approach," Madden says. "In addition, Dartmouth has an extremely strong culture of mentoring, which is a really critical aspect of COBRE success."

The iTarget Molecular Tools Core will help investigators with difficult-to-produce protein targets. (Pictured: an engineered system for microbial production of human lysozyme.)

The project establishes scientific core facilities to provide technical and laboratory tools for the research. A "molecular tools core," co-directed by engineering professor Karl Griswold and chemistry professor Jon Kull '88, will facilitate the engineering of proteins for specific research projects. There is also a "molecular interactions and imaging core," co-directed by chemistry professor Dale Mierke and Geisel biochemistry and cell biology professor Henry Higgs, which helps researchers visualize the processes at work in cells using a range of imaging technologies.

A third, administrative core will coordinate a shared seminar series, retreats, "and, most important of all, the mentoring of the junior faculty," Madden says.

The project will initially fund four junior projects, but as the work progresses, some of these researchers will "graduate" as their projects receive independent NIH funding. Then new junior faculty will be selected to take those spots. In addition, if iTarget is funded for the two additional five-year periods, the hope is that it will become a fully self-supporting institute, Madden says.

The mission of the iTarget project is also to accelerate the exchange of information between early discovery and early-stage target drug development, Madden says, "but with the idea that in studying diseases, researchers gain a better understanding of basic biological processes."

"The pitch that we made, and I think this is central to our philosophy, is the idea that it isn't a one-way street, that there's really a reciprocal relationship between thinking about basic biology and thinking about disease," he says.

While Dartmouth has undertaken COBRE projects before, iTarget relies particularly strongly on interactions between the faculties of Arts and Sciences, Geisel, and Thayer, Madden says.

"We have the expertise of the chemistry department in creating molecules; we have the expertise of the computer science department in using predictions to understand how molecules interact; we have Thayer engineering proteins; we've got the cancer center working on diseases at the cellular level; and we've got biology looking at the most fundamental ways that cells work," Madden says.

"This is a reflection of Dartmouth’s commitment to interdisciplinary research and teaching and to the fact that faculty expertise in this area is distributed all over campus."