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Rachelle Gaudet, Ph.D.

Harvard University
Dept. of Molecular & Cellular Biology
7 Divinity Avenue, SF 229B
Cambridge, MA 02138
Telephone: 617 495-5616
Fax: 617-496-9684
Email: gaudet@mcb.harvard.edu
Predocs: 1 Postdocs: 3 Completed PhD's: 0

  

We use a combination of x-ray crystallography and other biophysical and biochemical techniques to study the proteins involved in signaling and transport through biological membranes. The main project in the lab is to study the structure and function of “Transient receptor potential” (TRP) channels. The goal is to elucidate the gating mechanism of TRP ion channels involved in temperature sensing and understand modulatory interactions of proteins and small molecules with TRP channels. We focus on the temperature-sensing TRP channels such as TRPV1, TRPV2, and TRPM8. Several temperature-sensing TRP channels like TRPV1 and TRPV2 are expressed in nociceptor neurons, and therefore responsible for pain sensations in response to noxious stimuli. Therefore, with structures of these TRP channels we will be better equipped to design chemical inhibitors, which could potentially be used therapeutically.

Our long-term objective is to see how these TRP channels are gated by temperature and other chemical and physical stimuli at atomic resolution; therefore we prepare crystalline samples of isolated domains and complete channels for x-ray crystallography and structure determination and analysis. We also develop biochemical and biological assays, including electrophysiology, to address questions about TRP channel function.

We have additional projects on TAP, the transporter associated with antigen processing, and on divalent metal transporters of the NRAMP family. By applying similar techniques to different molecular targets, there is a lot of synergy between these projects on seemingly distantly related macromolecules.

 

References:

  • S. Misaghi, Z.-Y. J. Sun, P. Stern, R. Gaudet, G. Wagner and H. L. Ploegh (2004) A structural and functional analysis of the human cytomegalovirus US3 protein. J. Virol. 78, 413-423.
  • S. Misaghi, P. J. Galardy, W. J. N. Meester, H. Ovaa, H. L. Ploegh, and R. Gaudet (2005) Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate. J. Biol. Chem. 280, 1512-1520.
  • E. Procko, G. Raghuraman, D. C. Wiley, M. Raghavan, and R. Gaudet (2005) Domain boundaries are identified within the N-termini of TAP1 and TAP2 important for tapasin binding and tapasin-mediated increase in peptide loading of MHC class I. Immunol. Cell Biol. 83, 475-82.
  • X. Jin, J. Touhey, and R. Gaudet (2006). Structure of the N-terminal ankyrin repeat domain of the TRPV2 ion channel. J. Biol. Chem. 281, 25006-25010.
  • E. Procko, I. Ferrin-O’Connell, S.-L. Ng, and R. Gaudet (2006) Distinct structural and functional properties of the ATPase sites in an asymmetric ABC transporter. Mol. Cell in press.