Francesco TombolaAssistant Professor, Physiology & Biophysics |
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Research Interests |
Mechanisms of chemical and electrical sensing in excitable cells, ion channels and receptor enzymes | |
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Research Abstract |
We are interested in the molecular mechanisms by which excitable cells detect chemical and physical cues at their plasma membrane and then convert these cues into intracellular signals. Our approach is to combine fluorescence microscopy, electrophysiology, synthetic chemistry, biochemistry and molecular biology to make dynamic measurements in live cells of the following events: 1) the protein motions of ion channels that underlie signal detection, 2) the molecular events that couple the sensing process to the movement of the “gates” of ion-conducting effectors, 3) the ligand-binding events that drive or modulate the transduction process. As a paradigm, we study the super-family of proteins containing voltage-sensing domains (VSDs). This family comprises the channels that respond to voltage and are responsible for the generation and propagation of the action potential in nerves and muscles, as well as channels that sense chemical stimuli and are involved in vision, touch, olfaction, taste, and thermal perception. Currently our research focuses on the link between voltage sensing and ion permeation across the VSDs of Kv potassium channels and the Hv1 proton channel. In thermo-sensitive TRP channels we are investigating the role of the VSD in the integration of electrical, thermal and chemical stimuli. We are interested in finding new pharmacological tools to address the excessive cellular excitability that characterizes several neurological disorders. To this end, we are developing strategies for screening small molecules that can bind to the VSDs of voltage-gated channels and modulate their voltage sensitivity. | |
| Publications |
M. Pathak, L. Kurtz, F. Tombola and E. Isacoff (2005) The Cooperative Voltage Sensor Motion that Gates a Potassium Channel. J. Gen. Physiol. 125: 57-69. F. Tombola, M.M. Pathak and E.Y. Isacoff (2005) Voltage-sensing arginines in a voltage-gated channel permeate and occlude cation selective pores. Neuron 45: 379-88. F. Tombola, M.M. Pathak and E.Y. Isacoff (2005) How far will you go to sense voltage? Neuron 48: 719-25. F. Tombola, M.M. Pathak and E.Y. Isacoff (2006) How does voltage open an ion channel? Annu. Rev. Cell Dev. Biol. 22: 23-52. F. Tombola, M.M. Pathak, P. Gorostiza and E.Y. Isacoff (2007) The twisted ion-permeation pathway of a resting voltage-sensing domain. Nature 445: 546-9. M.M. Pathak, V. Yarov-Yarovoy, G. Agarwal, B. Roux, P. Barth, S. Kohout, F. Tombola and E.Y. Isacoff (2007) “Closing in” on the resting state of the Shaker K+ channel. Neuron 56: 124-40. F. Tombola, M.H. Ulbrich and E.Y. Isacoff (2008) The voltage-gated proton channel Hv1 has two pores, each controlled by one voltage sensor. Neuron 58: 546-56. |
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Professional Society |
AAAS, ACS, AHA, Biophysical Society, ISSNAF |
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| Graduate Programs |
Cellular and Molecular Biosciences |
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| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=5609 | |
| Last updated | 06/11/2009 | |