The Faculty

Focus

Structure-function relation in voltage dependent membrane proteins

Biography

Catholic University, Santiago, Chile, B.S.  , 1964, Biology 

Catholic University, Santiago, Chile, M.S., 1967, Biophysics

Catholic University, Santiago, Chile, Ph.D., 1968, Biophysics

Laboratory of Biophysics, NINCDS, NIH, Postdoc., 1969, Biophysics

Dept. of Physiol., Univ. of Rochester, NY, Postdoc., 1969-71, Physiology

 

1964-1968, Instructor in Physics, School of Medicine, Catholic University, Chile. 

1965-1969, Instructor, Laboratory of Neurophysiology, Catholic University, Chile. 

1969, Postdoctoral Fellow (Biophysics), Laboratory of Biophysics, NINCDS, NIH, Bethesda, MD

1969-1971, Postdoctoral Fellow, Department of Physiology, University of Rochester, N.Y. 

1972-1974, Assistant Professor, Department of Biology, Faculty of Sciences, University of Chile 

1974, Research Associate, Department of Physiology, University of Rochester School of Medicine 

1974-1977, Professor, Department of Biology, Faculty of Sciences, University of Chile 

1975-1976, Visiting Assistant Professor, Dept. of Physiol., Univ. of Pennsylvania School of Medicine  

1977-2005, Professor of Neuroscience, Department of Physiology, UCLA

2006-, Professor, Institute for Molecular Pediatric Sciences and Dept. of Biochemistry and Molecular Biology, University of Chicago.

Honors

1968-1969, Chilean Council for Scientific Research  

1969, Visiting Fellow, NIH 

1969-1971, Fellow Rockefeller Foundation

1977, Professor Rosenblueth Lecturer (I.P.N., Mexico) 

1984-1986, Executive Committee, Biophysical Society

1985-1987, Council Member, Society of General Physiologists 

1986-1987, Secretary of SOBLA 

1990, Keneth S. Cole Award 

1990, Society of General Physiologists Plenary Lecturer 

1992, The Third Magoun Lecture, Brain Research Institute, UCLA  

1998, Appointed as Leslie Scholar in Neuroscience 

1994, American Physiological Society Annual  Lecturer  

1995, Appointed as Susumu Hagiwara Professor of Neuroscience 

1999, Fellow of the Biophysical Society

2000, Annual Review Prize Lecture, The Physiological Society, U.K.

2002, Elected to the Latin American Academy of Sciences

2006, Elected to United States Academy of Sciences

2007, Doctor Honoris Causa University of Antwerp, Belgium &A.R. Martin Lecture

2008, Lillian Eichelber Cannon Professor

Research Interests

In voltage dependent channels, the electrical expression of their function is the ionic current which can be studied at the macroscopic level (the ionic current) and at the microscopic level (the single channel recording).  But in addition to the ionic current, in these molecules the rearrangement of internal dipoles and charged groups under the influence of the external electric field produce gating currents.  These currents are a direct expression of molecular rearrangements relevant to the operation (or gating) of the channel molecule. 

With the advent of molecular cloning techniques, we have been able to carry out these studies with a detail not possible before by recording gating currents of cloned Shaker K+ and Sodium channels and describing their electrical properties with high resolution.  Thus, we can modify the molecule to probe the role of specific amino acids in the voltage dependence and charge movement of the channel.

The main interest in the lab is the search for the dynamics of the molecular correlates of the function in membrane transport proteins.  This is being approached with physical techniques such as temperature effects and complex capacitance measurements in the frequency domain combined with mutations of the molecule and assessed by gating currents, macroscopic currents and single molecule recordings.  The correlation with structural changes are being monitored with optical techniques using real time fluorescence spectroscopy including lifetimes, changes in intensity and fluorescence resonance energy transfer from probes attached to strategic sites in the molecule of interest while being functional in the membrane.

Select Papers

  1. Lee, Elizabeth E.L., Francisco Bezanilla. (2017). Biophysical Characterization of Genetically Encoded Voltage Sensor ASAP1: Dynamic Range Improvement. Vol 113, p2178–2181. 

    Brugarolas, Pedro,  Jorge E. Sánchez-Rodríguez, Hsiu-Ming Tsai, Falguni Basuli, Shih-Hsun Cheng, Xiang Zhang, Andrew V. Caprariello, Jerome J. Lacroix, Richard Freifelder,  Dhanabalan Murali, Onofre DeJesus, Robert H. Miller, Rolf E. Swenson, Chin-Tu Chen, Peter Herscovitch, Daniel S. Reich , Francisco Bezanilla & Brian Popko. (2018). o image CNS demyelination. Scientific Reports 8:607 | DOI:10.1038/s41598-017-18747-3.

    Mathur, Chhavi, Kory R. Johnson, Brian A. Tong, Pablo Miranda, Deepa Srikumar, Daniel Basilio, Ramon Latorre, Francisco Bezanilla & Miguel Holmgren. (2018). Demonstration of ion channel synthesis by isolated squid giant axon provides functional evidence for localized axonal membrane protein translation. Scientific Reports 8:2207 | DOI:10.1038/s41598-018-20684-8.

    Carvalho-de-Souza, Joa˜o L. Bernardo I. Pinto, David R. Pepperberg, and Francisco Bezanilla. (2018) Optocapacitive Generation of Action Potentials by Microsecond Laser Pulses of Nanojoule Energy Biophysical Journal 114, 283–288.

    Nanazashvili, Mikheil , Jorge E. Sánchez-Rodríguez, Ben Fosque, Francisco Bezanilla, Henry Sackin. (2018). LRET Determination of Molecular Distances during pH Gating of the Mammalian Inward Rectifier Kir1.1b. Biophysical Journal, Vol. 114, p88–97

    Carvalho-de-Souza JL, Bezanilla F. (2018). Nonsensing residues in S3-S4 linker's C terminus affect the voltage sensor set point in K+ channels. J Gen Physiol. 150(2):307-321. doi: 10.1085/jgp.201711882.

    Parameswaran, R, J. Carvalho-de-Souza, Y. W. Jiang, M. J. Burke, J. F. Zimmerman, K. Koehler, A. W. Phillips, J. Yi, E. J. Adams, F. Bezanilla, B. Z. Tian. (2018). Photoelectrochemical modulation of neuronal activity with free-standing coaxial silicon nanowires. Nature Nanotechnology, doi.org/10.1038/s41565-017-0041-7.

    Bezanilla F. Gating currents. J Gen Physiol. 2018 Jul 2;150(7):911-932. doi: 10.1085/jgp.201812090. Epub 2018 Jun 25. Review. PubMed PMID: 29941430; PubMed Central PMCID: PMC6028497.

    Horng TL, Eisenberg RS, Liu C, Bezanilla F. Continuum Gating Current Models Computed with Consistent Interactions. Biophys J. 2019 Jan 22;116(2):270-282. doi: 10.1016/j.bpj.2018.11.3140. Epub 2018 Dec 14. PubMed PMID: 30612713; PubMed Central PMCID: PMC6350011.

    Carvalho-de-Souza JL, Nag OK, Oh E, Huston AL, Vurgaftman I, Pepperberg DR, Bezanilla F, Delehanty JB. Cholesterol Functionalization of Gold Nanoparticles Enhances Photoactivation of Neural Activity. ACS Chem Neurosci. 2019 Mar 20;10(3):1478-1487. doi: 10.1021/acschemneuro.

    Lee EEL, Bezanilla F. Methodological improvements for fluorescence recordings in Xenopus laevis oocytes. J Gen Physiol. 2019 Feb 4;151(2):264-272. doi: 10.1085/jgp.201812189. Epub 2019 Jan 3. PubMed PMID: 30606741; PubMed Central PMCID: PMC6363413.

    Jiang Y, Parameswaran R, Li X, Carvalho-de-Souza JL, Gao X, Meng L, Bezanilla F, Shepherd GMG, Tian B. Nongenetic optical neuromodulation with silicon-based materials. Nat Protoc. 2019 May;14(5):1339-1376. doi: 10.1038/s41596-019-0135-9. Epub 2019 Apr 12. PubMed PMID: 30980031; PubMed Central PMCID: PMC6557640.

    Acarón Ledesma H, Li X, Carvalho-de-Souza JL, Wei W, Bezanilla F, Tian B. An atlas of nano-enabled neural interfaces. Nat Nanotechnol. 2019 Jul;14(7):645-657. doi: 10.1038/s41565-019-0487-x. Epub 2019 Jul 3. Review. PubMed PMID: 31270446; PubMed Central PMCID: PMC6800006.

    Carvalho-de-Souza JL, Bezanilla F. Noncanonical mechanism of voltage sensor coupling to pore revealed by tandem dimers of Shaker. Nat Commun. 2019 Aug 8;10(1):3584. doi: 10.1038/s41467-019-11545-7. PubMed PMID: 31395867; PubMed Central PMCID: PMC6687735.

    Bassetto CAZ Jr, Carvalho-de-Souza JL, Bezanilla F. Metal Bridge in S4 Segment Supports Helix Transition in Shaker Channel. Biophys J. 2019 Sep 5;. doi: 10.1016/j.bpj.2019.08.035. [Epub ahead of print] PubMed PMID: 31635788.