Modifying to adapt: the impact of lysine deacetylases in Leishmania parasite stage differentiation

• Grant number: 23/07783-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 15, 2024
• End date: August 14, 2025
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Nilmar Silvio Moretti
• Grantee: Suellen Rodrigues Maran
• Supervisor: Igor dos Santos Cestari
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: McGill University, MacDonald, Canada
• Associated to the scholarship: 21/13477-6 - DeaceLeish: investigating the role of lysine deacetylases in the regulation of mechanisms involved in the stage differentiation of Leishmania mexicana, BP.DR

Abstract

Leishmania is the etiologic agent of Leishmaniasis, a serious infectious disease, that can manifest itself in three main forms: cutaneous, mucocutaneous and visceral. During its life cycle, the parasite faces different environments and adapting to these conditions changes gene expression, translation and metabolism. Protein acetylation is regulated by two families of enzymes, lysine acetyltransferases (KATs), which add acetyl groups to the lysine residue, and lysine deacetylases (KDACs), which remove these groups. KDACs are divided into two classes: NAD+-dependent (sirtuins) and zinc-dependent (DACs). Proteomic analysis from our group revealed differential protein acetylation among the three main Leishmania mexicana stages (procyclic, metacyclic and amastigote), suggesting a central role of this modification during parasite differentiation. In order to better understand the function of protein acetylation in this process, we decided to characterize the DACs (DAC1, 3, 4 and 5) of L. mexicana. The preliminary data from our group presented here, demonstrate that DACs affect several aspects of parasite stage differentiation and investigating the possible mechanisms regulated by these enzymes will significantly contribute to our understating of Leishmania biology. Thus, in this BEPE proposal, in collaboration with Dr. Igor Cestari from McGill University, we will employ two cutting-edge approaches, Yeast Surface Display and CHIP-seq, to investigate the DACs partners and how the nuclear DAC3 and 4 affect chromatin structure and gene expression in Leishmania. (AU)