Principal Investigator Ram Sasisekharan
Project Website http://web.mit.edu/tox/sasisekharan/research/technology.html
One thrust of our work is geared towards the development and extension of a variety of technological platforms that could advance our understanding of human health and disease. We participate in this field, by coupling engineering and computational approaches to elucidate complex biomedical phenomena.
A core direction of our efforts is towards the development of innovative technological platforms to study the life sciences. The complex nature of glycans renders the study of their functions a formidable undertaking. Recent technical advances shed considerable light on glycan function through the elucidation of their fine chemical structure.
Enzyme Platforms: Within the fields of molecular biology and enzymology lie important avenues leading towards the analysis of glycan properties and function. Much like restriction enzymes selectively cleave DNA at specific sites, a variety of enzymes in nature degrade complex carbohydrates for the purposes of providing organisms nutrition and entry into host cells. Using molecular biology and enzymology techniques, we seek to harness these activities and systematically probe the importance of glycan components. Many of these enzymes independently could hold therapeutic value, either in their natural form or through their manipulation using protein engineering strategies.
Analytical Chemistry Platforms: Analytical chemistry platforms provide complementary information on various aspects of glycan structure. The relative paucity of available glycan material, the inability of investigators to amplify glycans, the high-negative charge of glycans, and their chemical heterogeneity however all serve to stymie glycan analysis. Our efforts have somewhat ameliorated this situation as we have described the development of a variety of platforms that make available intricate information regarding the nature of glycans.
Structure-Function Platforms: Through various experimental inquiries we have probed the 3-D nature of biomolecules that dynamically interact with glycans. These efforts included studies of the conformational geometry of glycans; X-ray crystallographic investigations; and computational models of glycan-protein interactions.
We have developed several model systems to study the modulation of protein activity by glycans. The most developed of these systems focuses on the fibroblast growth factor (FGF) family of proteins. These molecules comprise a transient component of the ECM responsible for the regulation of a wide range of physiological processes.
Biomedical Platforms: Several programs of study within our group probe novel pharmacological strategies. Our nanotechnology platform combines cutting edge drug delivery technology with therapeutic strategies to attack cancer in two ways- by both cutting the tumor’s blood supply and killing the cancer cells directly.