Two MGH investigators are among the first recipients of the new Transformative R01 (T-R01) Awards, established by the National Institutes of Health (NIH) to support innovative research projects that have the potential to overturn scientific dogma. Frederick Ausubel, PhD, of the Department of Molecular Biology, and Sylvie Breton, PhD, of the Program in Membrane Biology in the Center for Systems Biology, are among the 42 T-R01 recipients announced Sept. 24 by the NIH Director's Office. Reflecting the risky nature of the work supported, the five-year T-R01s do not have a fixed budget cap. In addition, five MGHers were among 55 recipients of five-year, $1.5 million New Innovator Awards.
Ausubel and his team will use a novel live-animal-model system to search for new types of antibiotics. Instead of seeking compounds that kill infectious agents in a laboratory dish, the new approach assesses a drug’s impact in worms and fruit flies with particular emphasis on ways to block the factors that cause illness or enable a pathogen to escape the immune response. The team expects that halting the disease process itself, rather than stopping microbial growth, might avoid the serious problem of antibiotic resistance.
Breton's project will follow up work that earned her team the 2008 Basic Research Joseph Martin Award. That investigation found that cells at the deepest layer of tissues lining bodily cavities, presumed to be primarily structural, actually extend to the surface where they sense hormones and pathogens and transmit signals to adjacent cells. Using a novel mouse model that permits simultaneous imaging of different types of cells in living animals, Breton’s team
will further investigate the role of these cells in tissues
of the male reproductive tract and respiratory system.
New Innovator Awardees
Mark Albers, MD, PhD, of MassGeneral Institute for Neurodegenerative Diseases
Employing novel mouse models that reveal how gene mutations associated with degenerative disorders, such as Alzheimer’s and Parkinson’s diseases, affect the connectivity and function of neural cir-cuits, the Albers lab will work to improve the understanding of these disease processes and to identify new therapeutic targets.
J. Rodrigo Mora, MD, PhD, of MGH Gastroenterology
Mora’s group will investigate the role of gut-homing T cells and retinoic acid in the regulation of the immune system, particularly gut immune tolerance of antigens in food and normal intestinal bacteria. Their work could lead to new ways of treating autoimmune disorders and boosting the immune re-sponses produced by vaccines against pathogens such as salmonella and HIV.
Sunitha Nagrath, PhD, of MGH BioMEMS Resource Center
Nagrath’s team will use MGH-developed microfluidic devices to investigate metastasis in colorectal cancer, with particular focus on bone-marrow-derived cells that make specific tissues susceptible to certain tumor types. Understanding the relationship between these circulating endothelial progenitor cells and tumor cells may help guide treatment and identify new therapeutic targets.
John Pezaris, PhD, of MGH Neurosurgery
Pezaris and his colleagues will work to create a high-fidelity machine-brain interface that communicates with neurological and sensory systems in a responsive and highly specific fashion, of-fering the potential of restoring sight to the blind, restoring touch to amputees and spinal cord injury patients, and improving healing after stroke or other brain injuries.
Patrick Purdon, PhD, of MGH Anesthesia
With advanced imaging technologies to measure the brain’s activity under general anesthesia, Purdon’s team will develop new anesthesia monitors tracking the activity of specific neural systems under-lying anesthesia and novel drug delivery techniques targeting those systems with the goal of reducing serious and potentially life-threatening side effects, including postoperative cognitive dysfunction or delirium, awareness during surgery and cardiorespiratory depression.