Study of the interaction between the microRNA pathway and the electron transport chain in C. elegans

Author(s)

Thiago Leite Knittel

• Document type: Master's Dissertation
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2019-06-19

Examining board members

Fernanda Marques da Cunha; Pedro Manoel Mendes de Moraes Vieira

• Advisor: Marcelo Alves da Silva Mori

Abstract

There is a worldwide trend towards an increase of the age of the population, a fact that brings socioeconomic and public health problems. Mitochondrial stresses and the microRNA (miRNA) pathway interact to delay phenotypes associated with aging, but the mechanism by which this occurs remains elusive. The study of the causal relationship between changes in these pathways and the aging process is challenging in mammals due to their long lifespan. A model that allows this type of study is the "Caenorhabditis elegans" (C. elegans), given the ease of genetic manipulation of the organism, its short life span and the aging pattern similar to that of humans. Thus, we performed a quantitative proteomic analysis with samples of "C. elegans" presenting mutations that lead to mild mitochondrial stress or with increased expression of components of the miRNA pathway. These worm strains exhibit increased longevity or stress resistance. We observed changes in pathways limited to a strain or common to more than one strain, some of these were promising to explain the interaction between miRNAs and mitochondrial stresses, such as "embryonic development and reproduction", or to explain the longevity of mitochondrial mutants, such as "amino acid biosynthesis". These pathways could be studied to identify new mechanisms of aging control that have the potential to become drug targets. It has already been shown that cells of a tissue can act in a determinant way to coordinate the aging process of the whole organism. Thus, we sought to isolate tissues of "C. elegans" to study how the mutants analyzed in this project affect different cell types. To do this, we validated in muscle cells a method of tissue isolation of "C. elegans" and constructed a next generation sequencing library with the sample obtained. This will allow the study of the pathways observed in this project in a tissue-specific manner. (AU)

• FAPESP's process: 17/03423-0 - Characterization of the tissue-specific alterations in protein expression with aging and caloric restriction in C. elegans
• Grantee: Thiago Leite Knittel
• Support Opportunities: Scholarships in Brazil - Master