Study of the association of chaperones on the formation of coacervates used as membraneless organelles models

• Grant number: 22/10151-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2023
• End date: May 28, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Carlos Henrique Inacio Ramos
• Grantee: Marcos Vinícius Aquino Queirós
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 23/12135-0 - The influence of molecular chaperones on alpha-synuclein aggregation in model biomolecular condensates, BE.EP.PD

Abstract

Complex coacervation from mixtures of oppositely charged macromolecules has attracted great attention in recent years due to the observation of liquid condensates present in the cells and formed by the complexation of biomolecules. These intracellular subcompartments are known as membraneless organelles (OSMs). They do not display a lipid membrane at the interface with the cytosol, as it is normally found in other organelles, and are present in the nucleus and cytoplasm of the cells. In addition, there is also evidence that morphological transitions from liquid to solid in these structures may be associated with pathological conditions. Studies indicate that the morphology of OSMs is strongly related to the folding of the proteins that constitute them. As a result, cells have developed mechanisms by which it is possible to maintain the native conformation of proteins in these organelles. Among them, there are the chaperones, a family of proteins involved in the folding of other proteins. It is reported that they are very abundant in OSMs, therefore, fundamental for their maintenance and possibly, in the prevention of diseases related to aging. Despite the knowledge gained over the last few years on the identification of many chaperones in OSMs, little is known about the mechanisms in which these biomolecules act in the folding of proteins within OSMs. Thus, this project aims to study the complexation of some chaperones with RNA and amyloidogenic proteins in order to understand, mainly, how the morphology of the prepared complexes can be modified with the presence of the chaperones as well as if they present protective effects. With this, it is expected to have a better understanding of phenomena that have been observed within the cells and that are fundamental for the understanding of certain diseases. (AU)