C. elegans Model for the Genetics of Adipogenesis

描述(由申请人提供)：我们的总体目标是阐明控制脂肪细胞发育和功能的机制。储存能量的能力，主要是以脂肪的形式，是许多高等生物体生命周期所必需的一种迷人的特性。不幸的是，脂肪积累的异常会产生包括肥胖在内的病理状态，肥胖正迅速成为全世界发病率和死亡率的主要原因之一。然而，调控脂肪细胞发育和生理的基因还没有完全被了解。无脊椎动物已被证明是基因发现和基因功能表征的强大工具。因此，有一个无脊椎动物模型来研究脂肪发育将是一件很棒的事情。我们有令人鼓舞的初步数据，表明线虫脂肪可能是这样一个模型，我们建议测试和利用这些初步观察。 具体的实验目的是：1.研究我们确定的线虫脂肪形成所必需的基因。我们将描述活着的蠕虫和哺乳动物系统中的基因。用微阵列技术研究线虫脂肪的转录图谱。我们将比较野生型蠕虫和缺乏脂肪储存的蠕虫的表达谱。然后，我们将分析蠕虫和哺乳动物系统中的显著基因。生病了。通过正向和反向遗传筛选鉴定线虫脂肪形成所需的基因。我们将通过RNAi和EMS突变改变基因功能来产生缺乏脂肪的蠕虫。然后，我们将描述负责基因的特征。我们的长期目标是了解哺乳动物的脂肪生成，希望了解基因和机制可以导致合理和有效的治疗，以减轻与肥胖和糖尿病相关的痛苦。

DESCRIPTION (provided by applicant): Our overall objective is to elucidate the mechanisms that control adipocyte development and function. The ability to store energy, primarily as fat, is a fascinating property that seems to be required for the life cycle of many higher organisms. Unfortunately, abnormalities in fat accumulation produce pathological states including obesity, which is rapidly becoming one of the major causes of morbidity and mortality throughout the world. Yet, the genes that regulate adipocyte development and physiology are not fully understood. Invertebrates have proven to be powerful tools for gene discovery and for characterizing gene function. So, it would be great to have an invertebrate model for fat development. We have encouraging preliminary data that suggests that C. elegans fat might be such a model and we propose to test and exploit these initial observations. The specific experimental aims are: I. To study genes we identified as necessary for C. elegans fat formation. We will characterize the genes in both living worms and mammalian systems. II. To characterize the transcriptional profile of C. elegans fat with microarrays. We will compare the expression profiles of wild-type worms and worms that lack fat stores. Then, we will analyze the salient genes in worms and in mammalian systems. Ill. To identify genes required for formation of C. elegans fat via reverse and forward genetic screens. We will generate worms that lack fat by altering gene function with RNAi and with EMS mutagenesis. Then, we will characterize the responsible genes. Our long-term goal is to understand mammalian adipogenesis with the hope that understanding genes and mechanisms can lead to rational and effective treatments to relieve the suffering associated with obesity and diabetes.