Phenotypic assays of intact organisms allow us to uncover the molecular mechanisms underlying complex biological processes that, like the crosstalk between nutrients, fat stores, and other tissues, cannot be reduced to biochemical or cell-based assays: Caenorhabditis elegans, a roundworm sharing 50% of its genes with humans, is particularly well suited for large-scale whole animal studies of complex biological processes because it is small, easy to grow, and its transparent skin allows us to follow molecular responses in the context of a living organism throughout its entire life cycle. This project will take advantage of functional genomics, next-generation sequencing, biochemical and cell biological approaches to find genes that link nutrient availability to fat storage and mobilization. Additionally, we will search for RNA-based mechanisms of metabolic regulation. Uncovering molecules and biological pathways executing and coordinating mechanisms of energy homeostasis could help us in the prevention and treatment of obesity and its associated metabolic syndrome.
Obesity has become a leading cause of death worldwide. Genetic components, as well as the environment contribute to the severity of the syndrome. Caenorhabditis elegans is a simple model organism, a roundworm, sharing 50% of their genes with humans. C. elegans has been successfully used to uncover genes and drugs relevant to human disease in the past. I am going to work on developing an enabling technology that will accelerate the discovery of genes that could predispose and compounds that could relief human disease. I will particularly focus on finding genes that control fat accumulation and compounds that promote lipolysis (the process of breaking down fats). Learning more about the molecular mechanisms that lead to the activation of lipolysis could allow us to manipulate the balance between fat storage and consumption. Drugs that activate the breakdown of lipids could be used as therapeutic agents for the treatment of obesity.
|Wählby, Carolina; Conery, Annie Lee; Bray, Mark-Anthony et al. (2014) High- and low-throughput scoring of fat mass and body fat distribution in C. elegans. Methods 68:492-9|