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

PoLS：线虫和其他模型生物代谢和产热的直接量热测量

• 批准号: 1206106
• 负责人: Michael Roukes
• 金额: $ 47.45万
• 依托单位: California Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1206106&HistoricalAwards=false
• 关键词: PoLS; Direct; Calorimetric; Measurements; Metabolism

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.

在本项目中，pi将直接测量土壤线虫秀丽隐杆线虫（C. elegans）和其他模式生物的代谢和产热，通过微流控量热仪记录生物的产热。该量热计基于加州理工学院开发的微流控量热计平台，具有卓越的性能，包括单个蠕虫发电量的2%的功率分辨率，0.5s的响应时间和片上蠕虫孵化，可以连续监测蠕虫活动超过48小时。秀丽隐杆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，因此将其作为主要研究对象。在这个节目中，这些被操纵的蠕虫的生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Cyclohexamine（靶向核糖体）和放线菌素D（靶向RN聚合酶I， II和III），将被用于研究这些途径对代谢的贡献，这将为秀丽隐杆线虫几种重要生化途径对整体代谢的相对贡献提供更清晰的图像。接下来，将研究成虫发育过程中饮食和饥饿对其代谢的影响。最后，研究具有延寿基因突变的线虫的代谢与寿命之间的关系。PI和联合PI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）。这位共同负责人还曾指导过高中生，其中一些人在暑假和课后的研究中被列为顶级期刊论文的共同作者。