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Structure-function
relationships of ion channels; Gene Discovery Project
Influenza Virus Ion Channel
Influenza continues to kill more people in the developed world than AIDS.
There are only two inhibitors of the virus that work for people who are
already infected, and one of them, amantadine, works by inhibiting the
ion channel contained in the virus particle. We study this ion channel
because of its importance in the virus and because it serves as a simple
model of ion channels in general.
Gene Discovery Project
By mutagenizing mice and screening them for specific functional defects,
scientists have been able to discover genes that are involved in the
various important biological processes and to create models for important
human diseases. An example of one important process is the circadian
clock, and the essential Clock gene of the mouse was discovered in our
department using this approach. My lab is using this process to identify
mutations affecting blindness and asthma.
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Selected References:
• Tian
C, Gao PF, Pinto LH, Lamb RA, Cross TA. (2003). Initial structural and dynamic
characterization of the M2 protein transmembrane and amphipathic
helices in lipid bilayers. Protein Sci. Nov;12(9):2597-2605.
• Paterson, RG, M Takeda, Y Ohigashi, LH Pinto,
and RA Lamb. (2003). Influenza B virus BM2 protein is an oligomeric integral
membrane protein expressed at the cell surface. Virology 306;7-17.
• Mould, J.A., R.G. Paterson, M. Takeda, Y. Ohigashi, P. Venkataraman,
R.A. Lamb and LH Pinto. (2003). Influenze B Virus BM2 Protein Has Ion Channel
Activity that Conducts Protons across Membranes. Developmental Cell 5: 175-184.
• Tian, C., K. Tobler, R. A. Lamb, LH Pinto
and T. A. Cross. (2002). Expression and initial structural insights from solid-state
NMR of the M2 proton channel from influenza A virus. Biochemistry 41: 11294-11300.
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