The role of CEPsh glia in the regulation of proteostasis and aging in C. elegans

• Grant number: 23/17778-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2024
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Principal Investigator: Evandro Araújo de Souza
• Grantee: Maria Fernanda Kobayashi Rossi
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 22/05851-8 - Mechanisms of regulation of proteostasis in peripheral tissues by the nervous system, AP.GR
• Associated scholarship(s): 25/04375-6 - Uncovering the Role of C. elegans CEPsh Glia in Immune Function and Pathogen Resistance, BE.EP.MS

Abstract

The cell non-autonomous regulation of the proteostasis in peripheral tissue by neurons in animals has been known for at least a decade. However, only recently it was observed that glial cells can also promote this type of regulation. In Caenorhabditis elegans, the activation of stress pathways (UPRER/XBP-1, UPRMT/JMJD-1.2 and HSR/HSF-1) in CEPsh astrocyte-like glial cells can extend lifespan. Additionally, animals lacking this cell type can be more sensitive to agents destabilizing proteostasis, such as tunicamycin. However, the mechanisms by which this cell type can regulate the organism's proteostasis have yet to be elucidated. In this project, we will first investigate whether glial activity is important for the increased longevity observed in some long-lived mutants (eat-2, daf-2 and raga-1) in which it has previously been described that the nervous system plays a central role in regulating longevity. The nematode C. elegans is one of the few models in which it is possible to remove the glia without neuronal death. This allows an in vivo investigation of the physiological consequences of the absence of this cell type. Thus, we will perform RNA-seq on the AGD2173 strain, which has the expression of a caspase protein under the regulation of the CEPsh-glia-specific promoter, thus leading to the elimination of these cells. The targets of interest with altered expression will be validated by qRT-PCR. In particular, we want to understand how glia participates in the regulation of systemic proteostasis. The analysis of the transcriptome of these animals may also reveal physiological changes in the animal's nervous system, which will be explored in depth. This project could be a pioneer in revealing the role of glia in aging, opening up the prospect of future studies in mammals.