Combining biophysics and nanotechnology for protein structural and functional studies

• Grant number: 13/50752-9
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2013
• End date: November 30, 2015
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Agreement: North Carolina State University
• Principal Investigator: Antonio José da Costa Filho
• Grantee: Antonio José da Costa Filho
• Principal researcher abroad: Alex Illirikovich Smirnov
• Institution abroad: North Carolina State University (NC State), United States
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 12/20367-3 - Structural and functional studies of the Golgi Re-Assembly and Stacking Protein (GRASP) from Cryptococcus neoformans, AP.R

Abstract

The main objective of this scientific collaboration achieved through exchange of students and PhO researchers will be in expanding the ongoing biophysical studies of Golgi reassembly and stacking protein (GRASP) that have been already carried out by the USP team by further developing and applying nanotechnology approaches developed by the NCSU team. GRASP is known to play the key role in the molecular mechanism of establishing cryptococcosis - a fungal disease caused by the yeast pathogen Cryptococcus neoformans. Cryptococcosis has high mortality rates in immunosuppressed individuais and is on the rise in recent years in Brazil primarily for the reasons of an increased incidence of AIOS and a widespread use of immunosuppressive drugs. Specific aims of the proposed scientific collaboration include: (1) Oeveloping and applying quartz crystal microbalance (QCM) nanostructured sensors to investigate binding of GRASP to lipid bilayers of defined curvature and (2) Employing nanostructured lipid bilayer membranes to promote protein crystal nucleation and allow for growing GRASP crystals for subsequent structural studies. Overall, this project aims at producing experimental data for structure-function correlation of C. neoformans GRASP that would pave the way for developing novel therapeutic approaches to cryptococcosis. The project also addresses fundamental questions of the role of GRASP in functioning Golgi apparatus as well as developing new nanotechnologies for biosensing and preparation of protein crystals from "hard-to-crystallize" peripheral and membrane proteins. (AU)