The interplay between epigenetics, metabolism, and cell cycle in Trypanosoma cruzi

• Grant number: 22/08691-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 01, 2022
• End date: November 30, 2022
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ariel Mariano Silber
• Grantee: Ana Paula de Jesus Menezes
• Supervisor: Richard Burchmore
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Glasgow, Scotland
• Associated to the scholarship: 19/21354-1 - Chasing for chromatine-associated proteins and histone PTMs patterns associated to cell stages and metabolic states in trypanosomes, BP.PD

Abstract

In this proposal, we aim to improve the biological knowledge of Trypanosoma cruzi focusing on correlating the interfaces among three research areas: metabolism, epigenetics, and cell cycle. The parasites' metabolic flexibility allows them to survive in different environments, like those found in distinct hosts. The parasites can reprogram cellular functions, including metabolism, retaining the memory of this reprogramming during several replications and infection cycles. Besides, it could modulate the progression of the cell cycle as a function of the environmental and nutritional conditions. Moreover, using proteomics public data from nuclei and chromatin, we verify the presence of metabolic enzymes that provide local pools of critical metabolites for histone post-translational modification (PTMs). In turn, it could change the chromatin structure and function and modulate the DNA replication. Our primary goal in this proposal is to evaluate the effect of different cell cycle phases on the nuclear proteins, and the global pattern of histone PTMs. We expected to generate a global map of proteomic changes through the cell cycle and shed light on the underestimated link between cell cycle, metabolism, and epigenetics. (AU)