A dynamic subcellular map of the proteome of human chondrocytes undergoing cellular senescence

• Grant number: 23/04104-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: August 01, 2023
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Ana Marisa Chudzinski-Tavassi
• Grantee: Hellen Paula Valerio
• Supervisor: Kathryn S. Lilley
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: University of Cambridge, England
• Associated to the scholarship: 22/01892-1 - New molecular targets identification and validation of anti-inflammatory peptides applying distinct mass spectrometry-based proteomics approaches, BP.PD

Abstract

Senescent cells accumulate in many vertebrate tissues with age and contribute to many age-related diseases. Age is a risk factor for osteoarthritis, a chronic condition characterized by articular cartilage degeneration that causes pain and physical disability. Senescent chondrocytes are a possible therapeutic target for treating degenerative diseases and are susceptible to senomorphic drugs. Having in mind that the Center of Excellence in New Target Discovery (CENTD) is interested in identifying and validating new molecular targets and signaling pathways involved in osteoarthritis, we are proposing to explore new biological mechanisms and signaling events underlying chondrocyte senescence. We are also interested in understanding how an anti-inflammatory venom-derived peptide (pMb2) screened by CENTD over the last years modulate senescence in chondrocytes. To reach those aims, we are proposing to use an innovative method termed spatial proteomics, which enables a high resolution, global interrogation of the spatial dynamic of the proteome in cells under stress. The project will be conducted in collaboration with the laboratory of Professor Kathryn Lilley at University of Cambridge, who pioneered method development in the spatial proteomics field, providing robust, flexible and state-of-the-art tools to capture the dynamic cellular patterns we seek to study. We believe this collaboration can bring benefits both in terms of identifying new molecular targets involved in osteoarthritis and in terms of bringing an innovative methodology to CENTD and Instituto Butantan. (AU)