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)
Scientific publications
(12)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ARAUJO, SARA A.;
MARTINS, GUSTAVO H.;
QUEL, NATALIA G.;
ARAGAO, ANNELIZE Z. B.;
MOREA, EDNA G. O.;
BORGES, JULIO C.;
HOURY, WALID A.;
CANO, MARIA I. N.;
RAMOS, I, CARLOS H.
Purification and characterization of a novel and conserved TPR-domain protein that binds both Hsp90 and Hsp70 and is expressed in all developmental stages of Leishmania major.
Biochimie,
v. 182,
p. 51-60,
MAR 2021.
Web of Science Citations: 0.
ROCHA, MARINA CAMPOS;
MINARI, KARINE;
FABRI, JOAO HENRIQUE TADINI MARILHANO;
KERKAERT, JOSHUA D.;
GAVA, LISANDRA MARQUES;
DA CUNHA, ANDERSON FERREIRA;
CRAMER, ROBERT A.;
BORGES, JULIO CESAR;
MALAVAZI, IRAN.
Aspergillus fumigatusHsp90 interacts with the main components of the cell wall integrity pathway and cooperates in heat shock and cell wall stress adaptation.
Cellular Microbiology,
v. 23,
n. 2
FEB 2021.
Web of Science Citations: 1.
QUEL, NATALIA G.;
PINHEIRO, GLAUCIA M. S.;
RODRIGUES, LUIZ FERNANDO DE C.;
BARBOSA, LEANDRO R. S.;
HOURY, WALID A.;
RAMOS, I, CARLOS H.
Heat shock protein 90 kDa (Hsp90) from Aedes aegypti has an open conformation and is expressed under heat stress.
International Journal of Biological Macromolecules,
v. 156,
p. 522-530,
AUG 1 2020.
Web of Science Citations: 0.
BATISTA, FERNANDA A. H.;
RAMOS, JR., SERGIO L.;
TASSONE, GIUSY;
LEITAO, ANDREI;
MONTANARI, CARLOS A.;
BOTTA, MAURIZIO;
MORI, MATTIA;
BORGES, JULIO C.
Discovery of small molecule inhibitors of Leishmania braziliensis Hsp90 chaperone.
Journal of Enzyme Inhibition and Medicinal Chemistry,
v. 35,
n. 1,
p. 639-649,
JAN 1 2020.
Web of Science Citations: 0.