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

在本项目中，PI将通过微流态量热仪记录线虫和其他模式生物的产热情况，直接测量线虫土壤蠕虫和其他模式生物的代谢和产热作用。该量热仪基于加州理工学院开发的微流体量热仪平台，将具有卓越的性能，包括单条蠕虫发电量的2%的功率分辨率、0.5s的响应时间和芯片上的蠕虫孵化，使其能够连续监测蠕虫的活动超过48小时。线虫是一种重要的模式生物，在生物学研究中得到了广泛的应用，因此将成为研究的主要对象。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，一些针对不同生化途径的小分子抑制剂，如环磷酰胺(靶标核糖体)和放线菌素D(靶标RN聚合酶I、II和Amp；III)，将被用来研究这些途径对代谢的贡献，这将提供更清晰的图像，几个重要的生化途径对线虫整体代谢的相对贡献。接下来，我们将研究饮食和饥饿对成虫发育过程中新陈代谢的影响。最后，将研究具有延长寿命基因突变的蠕虫的新陈代谢和寿命之间的关系。国际和平协会和联合国际组织致力于传播技术、宣传和教育。加州理工学院的卡夫利纳米科学研究所有能力进行中等规模的设备生产。在过去的二十年里，PI和Co-PI积极参与了加州理工学院的暑期本科生研究计划(SURF)和少数民族本科生研究计划(MURF)。联合PI也有指导高中生的记录，其中一些人根据他们的暑期和课外研究被列为顶级期刊论文的联合作者。

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.