Board Member: 2005 - 2009
My group studies the mechanisms by which anchorage-dependent cells interact with their substrates in the context of several processes; cell attachment, cell migration, cell-cell signaling, differentiation and development. Because the natural substrates comprise complex proteins and polysaccharides, we use self-assembled monolayers (SAMs) of alkanethiolates on gold as model surfaces. SAMs that present a limited number of relevant groups in controlled environments permit the elucidation of cell-substrate interactions at the molecular scale. Our work combines expertise in organic synthesis, molecular recognition, preparative and analytical surface chemistry, and cell biology. A description of one project follows.
Cell Migration. The migration of neural cells along an immobilized gradient of the carbohydrate N-acetylglucosamine is important for establishing the organization of the nervous system. Migrating cells use a membrane-localized galactosyltransferase as a receptor to bind the carbohydrate; yet it is not known whether this receptor functions solely as a cell-adhesion molecule, or also as an enzyme that glycosylates the substrate. By studying cell migration on SAMs that present gradients of GlcNAc and related carbohydrates, we are defining the role of the receptor. This well-defined model system is also useful for studying several related aspects of cell migration.
Sequence-Specific Recognition of RNA. The second main interest of my group is the design and synthesis of ligands that bind RNA. Neomycin B is a naturally occurring aminoglycoside antibiotic that binds the HIV-1 Rev-binding element, an RNA molecule 30 nucleotides in length. By synthesizing analogs of the natural product we are establishing the critical structural features that confer specificity in binding RNA. Our goal is to use this information to guide the design of non-natural ligands for recognition of other RNA sites. We also explore strategies for recognition using protein and nucleic acid structures.