Characterization of a gain-of-function mutation that suppresses defects in MAP Kinase signaling in C. elegans (2024)

Undergraduate: Yasmine Ackall

Faculty Advisor: Rob Dowen
Department: Biology, Cell Biology and Physiology

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Proper distribution of lipids between tissues is essential to fuel biological processes that require large energy investments, like growth and reproduction. Misregulation of lipid allocation underlies several metabolic diseases such as diabetes, obesity, cardiovascular disease, and cancer. Lipid allocation is regulated by environmental and nutritional inputs; however, the specific pathways involved in making these complex metabolic decisions are poorly understood. Using Caenorhabditis (C. elegans), we seek to investigate the molecular signaling pathways that coordinate lipid homeostasis. In C. elegans, FLR-4, a conserved component of the Mitogen Activated Protein Kinase (MAPK) pathway, is an essential regulator of lipid homeostasis. Thus, flr-4 mutants are slow growing, small in body size, and display impaired lipid homeostasis. To explore other genes that may function in concert with flr-4, we performed a forward genetic screen for mutations that suppress the flr-4 mutant phenotype and identified a gain-of-function mutation in the sca-1 gene as a candidate suppressor of flr-4. sca-1 encodes a Sarco-Endoplasmic Reticulum ATPase (SERCA) that is essential for calcium ion transport and regulates the C. elegans defecation cycle, providing novel insight into the mechanisms that support lipid homeostasis and development. In this study, we aim to characterize the sca-1 gain-of-function allele and understand how it promotes growth in the absence of the FLR-4 MAPK pathway.