With a new five-year, $11.5 million grant from the National Institutes of Health, Brown University will expand its research in computational biology and launch a new Center of Biomedical Research Excellence (COBRE), which will support five early career faculty members as they tackle the genomics underlying diseases such cancer, preeclampsia and severe lung infections.
"There's data and then there's information," said David Rand, director of the new center and chair of the Department of Ecology and Evolutionary Biology (EEB). "Turning data into information you can use for something is what computational biology is all about."
The new center will bring together diverse teams of researchers to generate new insights to advance medicine and health, said David Savitz, Brown's vice president for research.
"Brown scientists and students from a number of departments around the University -- from computer science and applied mathematics to biology, medicine and public health -- have been working collaboratively to understand and realize the benefits of advanced genomics," said Savitz, who is also a professor in the School of Public Health. "This new COBRE will expand those programs to help move Brown to the forefront of this exciting, promising field of research."
Young field, rich history
In the early 1990s, the advent of genome sequencing turned molecular biology into a "big data" science where computation became a crucial tool for life sciences research, Rand said. Recognizing this emergence, Franco Preparata, computer science professor emeritus, guided Brown in launching one of the first undergraduate computational biology majors in the country.
"It was a very Brown thing to start at the undergraduate level," said Rand, who helped to establish the program.
Their vision was to build on that foundation. About a decade later under the University's Plan for Academic Enrichment, the program grew into the Center for Computational Molecular Biology. CCMB recruited five faculty members and facilitated research and collaboration among faculty in applied mathematics (Professor Charles Lawrence), computer science (Professors Sorin Istrail and Ben Raphael), the Division of Biology and Medicine (Professors Dan Weinreich and Sohini Ramachandran). In the years since its founding, existing faculty members from departments in BioMed and Public Health have helped increase the breadth of CCMB.
CCMB researchers have developed innovative methods to analyze complex genomics data sets. For example, Sohini Ramachandran, Manning Assistant Professor of Ecology and Evolutionary Biology, has developed analyses to discover how humans have diversified throughout history as they migrated out of Africa to the rest of the world. As part of the COBRE project, she will direct new efforts to uncover population-specific genomic signatures of cancer risk.
New projects, capabilities
The new COBRE will expand such collaborations and capabilities even further, Rand said, in part by substantially bolstering the University's infrastructure. To date, computational biology researchers have had to develop their own in-house technical capabilities, but the COBRE will build a research core where expert staff will be able to develop and code technical implementations for the center's researchers, freeing valuable time and resources in their own labs. This COBRE data analysis core will be co-directed by Associate Professors Casey Dunn from EEB and Zhijin (Jean) Wu from the Department of Biostatistics in the School of Public Health.
The center will directly fund research of five teams of scientists in which younger faculty members will pursue studies related to human disease under the mentorship of two more senior professors: one with expertise in computing and mathematics and another with expertise in biology and medicine. The COBRE will further support researchers with an administrative core that will support new seed projects to increase the breadth of users across the University. In addition to staffing in individual labs, the grant will allow the University to hire four new technical staff members to expand the COBRE Computational Core. These resources will contribute to the integration of related programs across the University including the Data Science Initiative, the Data Science Practice group and the Brown Center for Biomedical Informatics.
Five projects will get underway beginning June 1:
Amanda Jamieson, assistant professor of molecular microbiology and immunology, will study bioinformatics data to identify the genomic and cellular mechanisms underlying tolerance of viral and bacterial coinfection in the lung. Her mentors will be Dr. Jack A. Elias , dean of medicine and biologic sciences, and Wu.
Nicola Neretti, assistant professor of biology, will use bioinformatics screening of a fruit fly model to identify new drug targets for extending healthy lifespan. He'll work with mentors Rand and Charles Lawrence, professor of applied mathematics.
Ramachandran will develop new computational and analytical methodologies to identify risk genes for leukemia that differ in incidence across ethnic groups and genders. Her mentors will be Lawrence and Valerie Knopik, associate professor of psychiatry and human behavior at Brown and Rhode Island Hospital.
Alper Uzun, assistant professor of pediatrics (research) will test the hypothesis that variants in a refined set of gene candidates underlie the complex basis of preeclampsia. He'll work with Dr. Jim Padbury, William and Mary Oh - William and Elsa Zopfi Professor of Pediatrics at Brown and Women & Infants Hospital, and William Fairbrother, associate professor of biology.
Shipra Vaishnava, assistant professor of molecular microbiology and immunology, will study the spatial variation in the gut microbiome in response to antimicrobials and immunity pathways that can inform aspects of human irritable bowel disease (IBD). Her mentors will be Professor Richard Bennett from her department and Professor Mitch Sogin from the Marine Biological Laboratories.
Over the last 20 years, Brown and its affiliated hospitals have earned several other COBRE grants for research in areas ranging from human behavior to stem cells to skeletal health. Following the initial 5-year award period, COBRE grants can be renewed for and additional two five year periods, but the final 5-year award must focus more on continued sustainability of the research cores established in the COBRE.