Cells are bounded by a lipid bilayer membrane, and a whopping 20-25% of our genes encode proteins embedded in these membranes, illustrating the importance of the membrane in cellular physiology. Our lab is broadly interested in the mechanisms of signaling and transport across cellular membranes that are enabled by these membrane proteins. Our research encompasses several protein families. For example, we study Nramp transporters that use a proton gradient to facilitate the entry of transition metal ions (iron and manganese) into cells. Beside conditions like anemia, hemochromatosis and susceptibility to pathogens, Nramp transporters are also associated with Parkinson-like neurological disorders. A second transporter family we investigate are ABC transporters that use ATP to fuel substrate transport, allowing us to make interesting comparisons on the mechanisms and evolution of different types of transmembrane transport proteins. Our current favorite signaling proteins are cadherins and TRP channels. The cadherin superfamily is important in cellular adhesion and signaling, particularly in the development of neuronal connections in our brain, and their malfunction is associated with developmental disorders like autism and schizophrenia, and neurodegenerative diseases. Several TRP channels are very important receptors in sensory perception, and we have focused on those involved in sensing temperature and painful stimuli. We use a variety of cell-based and in vitro biochemical assays, x-ray crystallography, and computational techniques (molecular dynamics simulations and bioinformatics analyses) to discover how these important proteins function in cells.
Rachelle Gaudet, PhD
Professor of Molecular and Cellular Biology, Harvard University
Structural Biology of Signaling and Transport Through Biological Membranes