Multiuser Equipment approved in grant 2020/02897-1: liquid chromatography system AKTA Go

• Grant number: 21/07927-9
• Support Opportunities: Multi-user Equipment Program
• Start date: October 01, 2021
• End date: September 30, 2028
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Richard Charles Garratt
• Grantee: Richard Charles Garratt
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 20/02897-1 - Septin filaments: structure, polymerization and role in pathologies, AP.TEM
• EMU web page: Página do Equipamento Multiusuário não informada
• Type of equipment: Caracterização de Materiais - Análises Químicas - Cromatrografia líquida; Caracterização de Materiais - Análises Químicas - Análise de macromoléculas (GPC, LS)
• Manufacturer: Fabricante não informado
• Model: Modelo não informado

Abstract

Septins are cytoskeletal GTP-binding proteins involved in key cellular events including cytokinesis, vesicle trafficking and exocytosis. In humans, different septins self associate in a specific manner to form hexameric or octameric heterocomplexes. These interact via their extremities to form filaments which are capable of assembling into higher order structures. It is known that ectopic expression, deletion and/or mutation of septin-coding genes is associated with a wide range of pathologies including infertility, neuropathies and several types of tumour. In the nervous system, for example, where septins are abundant and involved in almost all stages of neuronal development, abnormalities in the expression and function of septins has been associated with aging and neurodegenerative disorders. A complete understanding of the physiological roles of septins and the dysfunctions which lead to different pathologies with which they are associated, demands a wider knowledge of all aspects of the biochemical context where septins are important components. Amongst others, critical aspects include a better understanding of: their three-dimensional structure and its relationship with GTP binding and hydrolysis; the phenomenon of polymerization and membrane association; the organization of higher-order structures (bundles, networks etc.) and their protein binding partners. With a view to clarifying several of these physiological aspects of septin function, the applicants (who are responsible for the greater part of our current knowledge concerning the structures of septins and their filaments) propose the use of e series of complementary approaches including the determination of further three-dimensional structures using X-ray diffraction and cryo-electron microscopy, complementary computational studies using simulation techniques and the identification of septin binding partners. Specific examples of the contributions we expect to make include understanding the mechanism associated with septin 2 cleavage by the NS3/2b protein from Zika virus which is believed to be associated with neuropathy and the study of the association between septins and botulinum toxin light chains. (AU)