Dissertations, Theses, and Capstone Projects

Date of Degree

9-2025

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy

Program

Biology

Advisor

Cathy Savage-Dunn

Committee Members

Alicia Meléndez

John Dennehy

Christopher Rongo

Monica Driscoll

Subject Categories

Cell Biology | Genetics | Immunity

Keywords

C. elegans, innate immunity, lipid metabolism, cell signaling

Abstract

The Bone Morphogenetic Proteins (BMPs) are secreted peptide ligands of the Transforming Growth Factor beta (TGF-β) family, initially identified for their roles in development and differentiation across animal species. They are now increasingly recognized for their roles in physiology and infectious disease. In the nematode Caenorhabditis elegans, the BMP ligand DBL-1 controls fat metabolism and immune response, in addition to its roles in body size regulation and development. DBL-1 regulates classical aspects of innate immunity, including the induction of anti-microbial peptides. We theorized that BMP-dependent regulation of fat metabolism could also promote resilience against microbial pathogens. We found that exposure to a bacterial pathogen alters total fat stores, lipid droplet dynamics, and lipid metabolism gene expression in a BMP-dependent manner. We further showed that fatty acid desaturation plays a major role in survival on a bacterial pathogen, while fatty acid β-oxidation plays a more minor role. We conclude that C. elegans mobilizes fatty acid metabolism in response to pathogen exposure to promote survival. We also investigated molecular and cellular mechanisms underlying BMP regulation of lipid metabolism through two unbiased methods: a DBL-1 suppressor screen and multi-omics. Our investigation provides a framework to study potential metabolic interventions that could support therapeutics that are complementary to antibiotic strategies.

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