Uncovering new regulators of DAF-16/FOXO expression

• Grant number: 18/07703-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2018
• End date: February 29, 2020
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Sweta Sarmah
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics, AP.TEM

Abstract

Insulin/IGF-1-like signaling (IIS) is central to growth and metabolism and has a conserved role in aging. In C. elegans, key components of this pathway are the insulin/IGF-1 receptor ortholog DAF-2 and the FoxO transcription factor ortholog DAF-16. Mutations in the daf-2 gene make worms live twice as long, and this phenomenon is entirely dependent on DAF-16 activation. Similarly, other conditions that extend lifespan in C. elegans, such as germline ablation and dietary restriction, require DAF-16. Preliminary data from our lab identified new potential regulators of DAF-16. In a RNAi screen, we found adr-1, nrde-1, wago-1, hda-1, and set-25 as positive regulators of a DAF-16 reporter transgene expression in germline-less worms. These genes are involved in histone modification and/or small RNA-mediated silencing pathways, and some participate in transgenerational inheritance. This suggests that DAF-16 and aging may be subject to epigenetic regulation through such previously unidentified mechanisms. In this project we aim to confirm by several methods whether DAF-16 is indeed controlled by these proteins and how. We also plan to test whether they participate in DAF-16-mediated lifespan regulation. With that, we hope to describe new mechanisms of aging, some of which could be epigenetically inherited and evolutionarily conserved.