Screening and characterization of Dicer regulators in C. elegans

• Grant number: 19/14391-8
• Support type: Scholarships abroad - Research Internship - Master's degree
• Effective date (Start): October 15, 2019
• Effective date (End): March 15, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal researcher: Marcelo Alves da Silva Mori
• Grantee: Willian Goulart Salgueiro
• Supervisor abroad: Adam Antebi
• Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: Max Planck Society, Dresden, Germany
• Associated to the scholarship: 17/22057-5 - Physiological effects and transgenerational inheritance induced by cholesterol-rich diet in Caenorhabditis elegans, BP.MS

Abstract

We are aging faster than ever before, so much that by 2050 it is expected that 22% of the world's population will represent people who are over their sixties. This is why understanding how lifespan and aging are controlled is now more important than ever. In this context, the miRNA processing pathway is of importance, since one of the enzymes that participates in this pathway - Dicer - was described by several studies as a key component in the control of the aging process. Dicer and global miRNA levels decrease with aging in mouse adipose tissue and in C. elegans, while fat-specific Dicer knockout mice and C. elegans where Dicer was knocked down age faster. Conversely, Dicer overexpression protects from oxidative stress and mildly extends C. elegans lifespan. Furthermore, Dicer is related to the onset of metabolic diseases such as diabetes, obesity and lipodystrophy, as well as different types of cancer. To gain new insights into how Dicer is regulated, we propose a whole-genome forwards genetics screen for Dicer regulators. For that we intend to screen a transgenic C. elegans worm that is free of commonly observed limitations, such as transgene inhibition by standard RNAi vectors and lack of endogenous regulatory elements (e.g., 5'- and 3'-UTRs). Finally, to obtain large scale and comprehensive data, we intend to employ a COPAS biosorter, which is not available in any Latin American country, to sort worms with differential Dicer expression in a fast, efficient, and unbiased manner. Characterization and validation of the identified targets will follow. This is expected to generate valuable data that will help us understanding how Dicer is regulated and how it can be modulated in order to delay aging. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BRAGA, DEISI L.; MOUSOVICH-NETO, FELIPPE; TONON-DA-SILVA, GUILHERME; SALGUEIRO, WILLIAN G.; MORI, MARCELO A. Epigenetic changes during ageing and their underlying mechanisms. BIOGERONTOLOGY, v. 21, n. 4, SI APR 2020. Web of Science Citations: 1.