Molecular Biophysics Graduate Student
Major Professor: Dr. Tim Cross
Lab: 4301 CSL (Chemical Sciences Laboratory)
Dynamics of M2 proton channel from Influenza A by solid state nuclear magnetic resonance. Influenza A virus infects respiratory tract epithelial cells. Seasonal flu was responsible for more than 6,000 deaths/year in the US alone between 1976 and 2007. M2 proton channel, a single pass αhelical transmembrane protein, is essential for the viral life cycle; defective M2 viruses are degraded in the lysosome and never make into the cell. The drug resistant M2 (containing the S31N mutation) has become dominant in recent seasonal flu and in the recent swine flu pandemic; to-date no new drug that targets M2 proton channel has been approved by the FDA. In spite of the consensus regarding the backbone structure of the transmembrane domain of M2 proton channel in its closed (inactive) state there is not much agreement on the conductance mechanism and on the structure of the channel in its conducting state. Several studies have shown that the M2 transmembrane domain has high conformational plasticity. Solid state Nuclear Magnetic Resonance (ssNMR) techniques enable the study of a whole frequency range of internal motions without any interference of the overall molecular tumbling that dominates relaxation phenomena observed in solution NMR. With ssNMR motional models can be dissected to a great extent with fewer assumptions; we intend to develop a motional model the backbone of M2 and for side chains of residues Val27 and Trp41, involved on the gating mechanism of proton conductance. The motional model will be combined with relaxation data which will be an important step in the comprehension of the dynamics of M2 wild type and the S31N mutant.
B.S. in Chemistry from the University of Sao Paulo, Sao Paulo, SP, Brazil
Master in Sciences from the University of Sao Paulo, Sao Paulo, SP, Brazil
- “M2 proton transporter in lipid bilayers: insight into the proton conductance mechanism, and early dynamics studies ” Gordon Research Conference: Protons & Membrane Reactions, February, 2012, Ventura CA
- “Dynamics in the transmembrane segment of the influenza A M2 proton channel” Experimental NMR Conference, April 2013, Asilomar CA.