Collaborative Research: Real-time Profiling of Regulatory Molecule Network in Adipocytes

这个项目的基本假设是脂肪形成和肥厚扩大是通过一个调节分子网络的协同作用来控制的。在这方面，在特定的目标1中，将产生基于荧光的报告质粒，用于实时基因表达和激活测量一组调节分子，如转录因子和信号激酶，这些分子在脂肪形成中起着很好的作用。在具体目标2中，将采用PI和co-PI实验室开发的多元统计方法来确定区分脂肪生成分化和肥大模式的调节分子。最后，在第三个具体目标中，将利用解偶联蛋白-1的表达来减少脂肪细胞肥大过程中的脂肪积累，并确定其对目标1和目标2中鉴定的区别调节分子的影响。肥胖是一个严重的健康问题。作为一种慢性疾病，肥胖会增加患许多疾病和失调的风险，包括心血管疾病、糖尿病甚至癌症。从长远来看，这一建议的结果将是通过阐明脂肪形成和肥大的调控基础来确定调节肥胖的其他分子靶点。在教育方面，该项目将成为一个新的综合研究和教育计划的基石。这项研究的主题将成为由PI讲授的系统生物学课程和副PI讲授的代谢和细胞工程课程的核心主题。

0651864 JayaramanThe basic hypothesis in this project is that adipogenesis and hypertrophic enlargement are governed through the concerted actions of a network of regulatory molecules. In that respect, in specific aim 1, fluorescence-based reported plasmids will be generated for real-time gene expression and activation measurement of a panel of regulatory molecules- such as transcription factors and signaling kinases- that have well established roles in adipogenesis. In specific aim 2 a multivariate statistical method developed in the laboratory of the PI and co-PI will be employed in order to determine regulatory molecules that discriminate the adipogenic differentiation and hypertrophy modalities. Finally in the third specific aim, the expression of uncoupling protein-1 will be utilized in order to decrease fat accumulation during adipocyte hypertrophy and determine its effect on the descriminant regulatory molecules identified from aims 1 and 2.Obesity is a big health problem. As a chronic condition, obesity increases the risk from many diseases and disorders, including cardiovascular disease, diabetes and even cancer. The result of this proposal- in the long term- will be to identify alternative molecular targets for regulating adiposity through the elucidation of the regulatory basis underlying adipogenesis and hypertrophy. Educationally, the project will form a cornerstone of a new integrated research and education program. The subject of this research will become a core topic of a course taught by the PI on Systems Biology and by the co-PI on metabolic and cell engineering.