PoLS: Direct Calorimetric Measurements of Metabolism and Thermogenesis of C. Elegans and Other Model Organisms

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In this project, the PIs will directly measure the metabolism and thermogenesis of nematode soil worm Caenorhabditis elegans (C. elegans) and other model organisms by recording the heat production of the organisms by a microfluidic calorimeter. The calorimeter is based on the microfluidic calorimeter platform developed at Caltech and will have superior performance, including a power resolution at 2% of single worm power generation, a response time of 0.5s and on-chip worm incubation enabling continuous monitoring of a worms activity for over 48 hours. C. elegans will serve as the major target because it is an important model organism that has been extensively used in biological research. In this program thermogenesis in these manipulated worms will be employed to differentiate metabolic pathways and study longevity. First, a number of small molecule inhibitors specific to different biochemical pathways, such as Cyclohexamine (targets Ribosomes) and Actinomycin D (targets RN Polymerases I, II & III), will be used to investigate the contribution of these pathways to metabolism, which will provide a clearer picture of the relative contribution of several important biochemical pathways to overall metabolism in C. elegans. Next, the effect of diet and starvation on the metabolism of adult worms will be studied during their development. Finally, the relation between metabolism and longevity for worms with life-extending genetic mutations will be investigated. The PI and co-PI are committed to dissemination of the technology, outreach and education. The Kavli Nanoscience Institute at Caltech is capable of moderate-scale production of devices. The PI and Co-PI have actively participated in Caltech's Summer Undergraduate Research Program (SURF) and Minority Undergraduate Research Program (MURF) for the past two decades. The co-PI has also has a track record of mentoring high school students, a number of whom have been included as co-authors on papers in top journals based on their summer and after-school research.