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The chaperome: study of the relationship of the structure of its components and the maintenance of proteostasis

Grant number: 17/26131-5
Support type:Research Projects - Thematic Grants
Duration: March 01, 2019 - February 29, 2024
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Carlos Henrique Inacio Ramos
Grantee:Carlos Henrique Inacio Ramos
Home Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas, SP, Brazil
Co-Principal Investigators:Julio Cesar Borges
Assoc. researchers:Leandro Ramos Souza Barbosa ; Lisandra Marques Gava Borges

Abstract

One of the most interesting challenges in science is the understanding of the structure/function relationship of proteins because these macromolecules are involved in virtually all cellular physiological functions. Accordingly, this knowledge can have several applications, including the production of proteins with specific functions and defined biotechnological applications. As the loss of the structure also leads to loss of function and to a high degree of cellular damage, there is also medicinal interest in this knowledge since it can generate strategies for therapeutic interventions with broad applications such as aging, stress, neurodegenerative diseases and tumor. The research groups gathered around this proposal have a high interest in the understanding of protein folding and the structure/function relationship of proteins. This research proposal focuses on the study of the chaperome, a cellular network aimed at the maintenance of homeostasis, which includes aiding the folding of several proteins, preventing unfolding in stress situations and promoting the recovery and degradation of protein aggregates. Additionally, the components of the chaperome are involved in several other complementary functions, among which the most important are maintenance of proteostasis in stress situations, signaling, phenotype stabilization, mitochondria biogenesis, immunity, preventing amyloidogenesis, etc. Our proposal aims at the production and characterization of the components of the chaperome and the investigation of the interaction between them and with client proteins. The proposal is divided between challenging but high-attainable goals and high-risk/high-gain objectives that will enable us to advance the frontier of knowledge in the area. Previous results have shown that different organisms have certain particularities in the structure/function relationship of the chaperome (for instance, the number and diversity of co-chaperones increases with organism complexity), showing that it is crucial to study the system of several species to obtain information on the functioning of this system. The same reasoning can be extrapolated to organelles since each one has its own set of chaperones/Hsps. Therefore, we chose highly relevant targets for global science and potential applications in Brazil: human being, sugarcane, Aedes aegypti, Leishmania sp, Plasmodium falciparum and yeast; cytoplasmic and mitochondrial. Therefore, this proposal has great potential to generate relevant knowledge both in the medical field, by generating strategies aimed at therapeutic intervention, and in biotechnology, by generating innovative processes in plants and microorganisms aiming to produce potential biotechnological tools. (AU)