Unveiling new therapeutic targets involved in proteostasis and aging through CRISPRa in C. elegans

• Grant number: 24/18123-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Physiology - Compared Physiology
• Principal Investigator: Evandro Araújo de Souza
• Grantee: Carlos Alberto Vergani Junior
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/05851-8 - Mechanisms of regulation of proteostasis in peripheral tissues by the nervous system, AP.GR

Abstract

Population aging is a major economic and healthcare challenge in the 21st century, with a projected 1.6 billion people over the age of 65 by 2050. In Brazil, 40% of the population is expected to be elderly in the coming decades. In this context, it is crucial to develop public policies and promote research focused on the health and quality of life of the elderly. Aging results from the accumulation of molecular and cellular damage, leading to chronic and neurodegenerative diseases. "Proteostasis," the balance in protein regulation, becomes less efficient with aging, contributing to diseases associated with the accumulation of misfolded proteins. Biological models, such as the nematode Caenorhabditis elegans (C. elegans), have been fundamental in aging research due to shared biological processes with humans. Studies show that genetic manipulation of proteostasis in C. elegans can slow aging and increase longevity. Advanced genetic techniques like RNAi and CRISPR-Cas9 are essential for exploring aging-related genes, with therapeutic potential for humans. This project aims to optimize the CRISPRa system, a gene activation tool in C. elegans, with the goal of identifying new genes related to proteostasis and longevity, aiming to discover potential therapeutic targets that can improve the quality of life for the elderly.