Mitochondrial dynamics during oogenesis

• Grant number: 17/50377-4
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2018
• End date: August 31, 2020
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Marcos Roberto Chiaratti
• Grantee: Marcos Roberto Chiaratti
• Principal researcher abroad: Hugh James Clarke
• Institution abroad: McGill University, Montreal, Canada
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 17/05899-2 - Effect of the knockout of mitofusins on mouse oocyte: implications to fertility and mitochondrial inheritance, AP.R

Abstract

This proposal is based on previous findings of M. Chiaratti's group, which with the expertise provided by the H. Clarke's group seeks to characterize mitochondrial dynamics in oocytes in greater depth, with potential implications to human welfare and health. The proposed scientific activities will investigate three hypotheses in mice: 1) Mfn1 conditional knockout (cKO) inhibits the P13K1Akt pathway and enhances mitochondria-endoplasmic reticulum (ER) contacts in oocytes, which is reversed in Mfn1 +Mfn2 cKO oocytes; 2) Mfn2 overexpression (OE), but not Mfn1 +Mfn2 OE, prevents oocyte growth and maturation; and, 3) mitophagy underpins the purifying filter against mutant mitochondrial DNA (mtDNA) in growing oocytes. Also, two one-day workshops on oogenesis will be organized in São Carlos (in 2018 and 2019) and M. Chiaratti will chair a session on folliculogenesis during the Annual Meeting of the Brazilian Society for Embryo Technology (SBTE) in which H. Clarke will contribute with a speech. The resources sought will cover the travelling and subsistence cost for Principal lnvestigators (Pls) between Montreal and São Carlos. At Federal University of São Carlos (UFSCar), M. Chiaratti studies mitochondria in the female germline and their effect on fertility and mtDNA inheritance. H. Clarke studies growth and meiotic maturation of the mammalian oocyte at McGill University. He is currently the Co-Editor-in-chief of Biology of Reproduction and has authored/co-authored over 50 publications and book chapters. (AU)