Investigation of the action of toxins in osteoclastogenesis and in lymphocytes activation: search of possible therapeutic targets

• Grant number: 18/01370-0
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): May 01, 2018
• Effective date (End): January 31, 2022
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Acordo de Cooperação: GlaxoSmithKline
• Principal Investigator: Irina Kerkis
• Grantee: Hugo Vigerelli de Barros
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival, AP.PCPE

Abstract

Osteoclasts acts in bones maintenance, repair and remodeling. Bone diseases such as Osteoporosis and Rheumatoid Arthritis have increased osteoclastogenesis, a devastating effect for bone loss. Therefore, there is a critical importance in the study of specific proteins or signaling pathways in the process of osteoclast differentiation. This process will be studied in a model of Peripheral Blood Mononuclear Cells (PBMCs), which will be stimulated by molecules isolated from venom of poisonous animals, which are preserved in the Center of Excellence for Research in Target Discovery (CENTD) biobank. PBMCs will also be cultured in the presence or absence of osteoclast differentiation process inducing factors, which will be suitable as controls for comparative analysis with the molecules screening. After the initial analysis, three or more molecules will be chosen to better elucidate the pathways involved in osteoclastogenesis. The pathways study, as well as the osteoclasts maturation, will involve different strategies, such as the bone reabsorption assay and the investigation of specific factors that are favorably or not involved with the differentiation process of these cells, aiming the identification of new targets for a better understanding of the pathways and molecules related to bone diseases.In parallel, we established a study model in PBMC and T lymphocytes (Jurkat-E6) stimulated or not by activation factors, in order to investigate the crotamine action, a polypeptide isolated from Crotalus durissus terrificus venom. Preliminary data show that crotamine has immunomodulatory activity in activated lymphocytes. Such activity will be investigated in vivo models: nude+/nude+, nude+/nude-, nude-/nude-. These models will elucidate targets involved in inflammatory and autoimmune diseases. (AU)