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

在本计画中，PI将直接量测线虫土壤蠕虫秀丽隐杆线虫（C. habditis elegans）的代谢与产热。elegans）和其它模式生物，通过微流体量热计记录生物的热产生。该热量计基于加州理工学院开发的微流体热量计平台，具有上级性能，包括2%的单蠕虫发电功率分辨率，0.5秒的响应时间和芯片蠕虫孵育，能够连续监测蠕虫活动超过48小时。C.由于线虫是生物学研究中广泛使用的重要模式生物，在这个项目中，这些被操纵的蠕虫的产热作用将被用来区分代谢途径和研究寿命。首先，将使用一些对不同生化途径具有特异性的小分子抑制剂，如环六胺（靶向核糖体）和放线菌素D（靶向RN聚合酶I、II和III），研究这些途径对代谢的贡献，这将更清楚地了解几种重要生化途径对C.优雅接下来，将研究在成虫发育过程中饮食和饥饿对蠕虫代谢的影响。最后，将研究具有延长寿命的基因突变的蠕虫的代谢和寿命之间的关系。主要研究者和共同主要研究者致力于传播技术、外联和教育。加州理工学院的Kavli纳米科学研究所能够进行适度规模的设备生产。PI和Co-PI在过去的二十年里积极参与加州理工学院的夏季本科生研究计划（SURF）和少数民族本科生研究计划（MURF）。共同PI也有指导高中生的记录，其中一些人已被列为基于他们的夏季和课后研究的顶级期刊论文的共同作者。

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.