Towards identification of molecular mechanisms of resistance to drugs and DNA reparation in Trypanosomatidae

• Grant number: 19/23605-1
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2022
• End date: September 30, 2023
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Agreement: Universidad de Antioquia (UdeA)
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Maria Carolina Quartim Barbosa Elias Sabbaga
• Grantee: Maria Carolina Quartim Barbosa Elias Sabbaga
• Principal researcher abroad: Omar Triana Chavez
• Institution abroad: Universidad de Antioquia (UdeA), Colombia
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Ana Maria Mejía-Jaramillo ; Julia Pinheiro Chagas da Cunha
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID

Abstract

Chagas disease (CD) and Leishmaniasis are major health problems in the Americas, being Brazil and Colombia, countries where these diseases are epidemiologically significant. Despite the important health burden of these diseases, there is little investment by pharmaceutical companies, and the governments from endemic countries assign limited resources to health care. In addition, there are a number of complications with the current drugs used for the treatment of both diseases, being the resistance one of the most important. Thus, the clear understanding of origin, establishment and consequences of resistance to drugs has the potential to provide solutions to the increasing risk of these neglected diseases, and the development of new alternatives to the treatment. Genetic changes, which can be a consequence of replication and repair processes, and epigenetic changes can alter gene expression levels in response to certain stimuli, including interaction with drugs. These changes can confer resistance to drugs by altering the expression of target genes or genes encoding drug efflux pumps or other genes. To reach new levels of knowledge, the goal of this proposal is to develop a highly collaborative multidisciplinary network with researchers expert in molecular biology, DNA replication, repair and epigenetics (Brazilian group) and researchers with expertise in CRISPR-Cas9 and chemotherapy of these diseases (Colombia group) in order to develop new tools to identify the mechanisms of action and resistance to drugs. (AU)