Genomic Regulators of Lipid Metabolism and Longevity in C. elegans

Summer 2023 Research Project at Scripps Research

Abstract

During my Summer 2023 internship at the Srinivasan Lab, The Scripps Research Institute, I focused on the HLH-11 feedback loop in C. elegans, which plays a crucial role in bridging fat oxidation with mitochondrial stress responses and lifespan regulation. The transcription factor HLH-11 is highly conserved and is known to regulate lipid metabolism, mitochondrial stress responses, and longevity. Understanding this feedback loop is significant as it can provide insights into the complex relationship between these physiological processes and their impact on overall health and aging.

My project involved several key components:

1. Cloning tissue-specific hlh-11 rescue constructs: This step aimed to dissect the tissue-specific roles of HLH-11, utilizing Gibson Assembly.
2. Creating a global hlh-11 knockout using CRISPR: This allowed us to observe the effects of completely removing hlh-11(3,387 bp) from C. elegans.
3. Crossing hlh-11 mutants with Phlh-11::hlh-11 GFP strains: This enabled visualization of HLH-11 expression and function in specific tissues.
4. NeuroPAL x hlh-11 GFP imaging: This innovative technique provided detailed images of the nervous system in the context of HLH-11 activity.
5. Lifespan experiments: Conducted in collaboration with another researcher, these experiments assessed how the manipulation of HLH-11 affected the organism’s longevity.

The significance of this research lies in its potential applications. By understanding the HLH-11 feedback loop, we can gain deeper insights into how lipid metabolism and mitochondrial stress responses are coordinated to influence lifespan. This knowledge could inform the development of interventions to modulate these processes in humans, potentially leading to new therapies for metabolic and age-related diseases. Additionally, given that HLH-11 and its pathways are conserved across species, findings from this research could have broad implications for understanding similar mechanisms in other organisms, including humans.

Overall, this project not only advanced our understanding of HLH-11’s role in C. elegans but also highlighted the intricate connections between metabolism, stress responses, and aging, offering potential pathways for future research and therapeutic development.

(May 2023 - August 2023)