Next Guestlecture: December 1st, 11:30, UZA 2, HS 4

07.11.2022

We are looking forward to host Prof. Bonnie Ann Wallace, University of London, for her lecture on voltage gated sodium-channels!

The MolTag Program  & the Lecture Series Pharma and Food invite you to the following lecture:

 

Voltage-Gated Sodium Channels as Targets for Treatment
of Neurological and Cardiovascular Diseases

by Prof. Bonnie Ann WALLACE, Institute of Structural and Molecular Biology,
Birkbeck College, University of London, London, UK

on: Thursday, December 1st, 2022, 11:30 a.m.

at:  UZA2, Josef Holaubek-Platz 2, 1090 Vienna;
Host: Assoc.Prof.Dr. Anna Weinzinger

Lecture Hall 4.

Abstract: Voltage-gated sodium channels (Navs) play essential roles in excitable tissues, and are important targets for analgesic, antiepileptic and cardiovascular drugs. The activation and opening of these channels result in the initial phase of the action potential. I will discuss our studies on the NavMs channel (1-4), including its high resolution (2.0 A) crystal structures, plus molecular dynamics (5), spectroscopic (6), mutational, cryoEM, bioinformatics (6), and electrophysiology studies of the channel that have enabled visualisation of the locations of the sodium ions in the channel cavity (3), binding sites of channel-blocking and channel-modulating drugs (4,6) and the transmembrane fenestrations that enable drug ingress into the channel (7), as well as the changes in the voltage sensor and the channel gate associated with ion transport and channel opening and closing. These studies have enhanced our understanding of the structural basis of function and disease-related mutations in Navs.

  1. Sula, Booker, Ng, Naylor, DeCaen, Wallace (2017) The complete crystal structure of an activated open sodium channel. Nature Communications 8:14205.
  2. Sula, Wallace, (2017). Interpreting the functional role of a novel interaction motif in prokaryotic sodium channels. J Gen Physiology149:613-622.
  3. Naylor, Bagnéris, DeCaen, Sula, Scaglione, Clapham, Wallace. (2016) Molecular basis of ion permeability in a voltage-gated sodium channel. Embo J 35:820-83
  4. Bagnéris, DeCaen, Naylor, Pryde, Nobeli, Clapham, Wallace, (2014) The prokaryotic NavMs channel as a structural and functional model for eukaryotic sodium channel antagonism.  Proc. Natl. Acad. Sci. USA 111:8428-8433.
  5. Ke, S., Ulmschneider, M.B., Wallace, B.A.*, and Ulmschneider, J.P.* (2018) Role of the interaction motif in maintaining the open gate of an open sodium channel.  Biophys J. 115:1-11.
  6. Zanatta, G., Sula, A., Miles, AJ., Ng, L., Torella, R., Pryde, D.C., DeCaen, P.G., Wallace, B.A. (2019) Valproic Acid Interactions with the NavMs Voltage-Gated Sodium Channel, Proc. Natl. Acad. Sci. (USA), 116: 26549-26554.
  7. Montini, Booker, Sula, Wallace, Comparisons of Voltage-Gated Sodium Channel Structures with Open and Closed Gates and Implications for State-Dependent Drug Design. 46:1567-1575.
  8. Sula, Hollingworth, Ng, Larmore,, DeCaen, Wallace (2021) A tamoxifen receptor within a voltage-gated sodium channel. Molecular Cell 81:1160-1169. Sait, Sula, Ghovanloo, Hollingworth, Ruben,Wallace, BA. (2020)   
  9. Cannabidiol interactions with voltage-gated sodium channels. eLife 9: e58593.

Biography: Bonnie Ann Wallace obtained her PhD in Molecular Biophysics and Biochemistry from Yale and did postdoctoral work (as a Jane Coffin Childs fellow) at Harvard and at the MRC Lab of Molecular Biology in Cambridge. She was an Associate Professor of Biochemistry at Columbia University, then Professor of Chemistry and Director of the Center for Biophysics at Rensselaer Polytechnic Institute, before moving her lab to the UK 30 years ago. Amongst other honours, she has been the recipient of the 2021 Khorana Prize, the Interdisciplinary Prize (Royal Society of Chemistry), the AstraZeneca Award (The Biochemical Society), Dayhoff Award (The US Biophysical Society), and is an Honorary Member of the British Biophysical Society and a Fellow of the (US) Biophysical Society, IUPAB, AAAS, and the Royal Society of Chemistry. Her research interests include the structure and function of voltage-gated sodium channels (molecular biology, physiology, crystallography, cryoEM, and drug interactions), and the development of new methods (especially for circular dichroism spectroscopy and bioinformatics tools for characterising proteins).

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