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Binding and interactions of Brazilian toxins to voltage-gated sodium channels: the rational search for new drugs

Grant number: 19/19799-5
Support type:Regular Research Grants
Duration: January 01, 2020 - December 31, 2021
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Cooperation agreement: BBSRC, UKRI
Principal Investigator:Ana Paula Ulian de Araujo
Grantee:Ana Paula Ulian de Araujo
Principal investigator abroad: Bonnie Ann Wallace
Institution abroad: University of London, England
Home Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Assoc. researchers:Denise Vilarinho Tambourgi ; Jose Luiz de Souza Lopes ; Manoel de Arcisio Miranda Filho
Associated research grant:14/15546-1 - Septins: comparative studies and the correlation between structure and function, AP.TEM

Abstract

Toxins present in the venom of poisonous animals specifically target ion channels present in the cell membranes of human and other organisms. For example, sodium channels, responsible for the initiation of the action potential in excitable cells can be hampered by formation of stable complexes with toxins, resulting in inactivation or modulation of the channel functions. The present proposal intends to form the underpinnings for a full study on ion channel-toxin interactions using native Brazilian toxins with a range of structural, biophysical and functional studies of sodium channels. Specifically, the proposal aims to investigate the action of new/novel natural toxins produced by Brazilian indigenous species, and their functional and binding effects on voltage-gated sodium channels. The proposal blends the expertise and experience of the UK partners in the production and crystallization of sodium channels, allowing it to be purified in Brazil, with the necessary skills for physiological, functional and complexation studies of these channels with native Brazilian toxins. Binding and electrophysiology assays, merged with structural studies of toxins-channels will provide evidence for specific ways of modulating ion channels, which could have value for biochemical industry. (AU)