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Does signalling during DNA replication stress drive genome diversity in Leishmania?

Grant number: 20/01883-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2020
Effective date (End): August 31, 2022
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Cooperation agreement: MRC, UKRI ; Newton Fund, with FAPESP as a partner institution in Brazil
Principal Investigator:Luiz Ricardo Orsini Tosi
Grantee:Jennifer Ann Black
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:18/14398-0 - UK:Brazil Joint Centre Partnership in Leishmaniasis (JCPiL), AP.TEM

Abstract

The genome of Leishmania is characterized by a remarkable plasticity that has been associated with the acquisition of drug resistance and with host adaptation. Here, we will explore if the parasite's signaling of replication 'stress' may underlie genome plasticity and diversity. The analysis of the ATR pathway, which is central to the detection and signaling DNA replication stress and damage, is key to understand the above questions. To date, there has been greater characterization of the Leishmania 9-1-1 complex, which is a key element at the early steps of the pathway. The main goal of this proposal is to extend the characterization of the ATR pathway and explore the structure and function of other key components of this orchestrated response. (AU)