Metabolite Sensing and Regulation of Protein Function

蛋白质功能的代谢传感和调节

基本信息

批准号：
10395458
负责人：
Hening Lin
金额：
$ 38.76万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2024-04-30
项目状态：
已结题

项目摘要

Metabolite Sensing and Regulation of Protein Function After the human genome is sequenced, one of the most important challenges in biomedical research is to understand how gene expression changes in response to various signals and stresses. In other words, understanding cell signaling mechanisms is of critical importance to understand life processes. This proposal focuses on how mammalian cells sense certain metabolites and use that information to regulate protein function. Common cellular metabolites, such as co-enzyme A, glutathione, and nicotinamide adenine dinucleotides, play important roles in various metabolic pathways. Many protein post-translational modifications also use these metabolites. Maintaining the concentrations of these metabolites is thus critically important. Cells and organisms must be able to sense these metabolites and use the information to regulate biological processes. However, very little is known about the sensing mechanisms for these metabolites. In this MIRA application, I will focus on using chemical biology techniques to identify how mammalian cells sense common metabolites to regulate protein function. Preliminary results indicate that this is a highly interesting and exciting area that warrant much more investigation. This a completely new research direction for my laboratory and is distinct from my previous and HHMI-supported research. The proposed research will identify many novel regulatory mechanisms of protein function by small molecule metabolites. This will in turn provide a better understanding of cell signaling and address one of the most important challenges in biomedical sciences in the postgenomic era. These regulatory mechanisms can also directly impact the development of therapeutics as they will help to develop allosteric inhibitors or activators of proteins.

蛋白质功能的代谢物传感和调节测序人类基因组后，生物医学研究中最重要的挑战之一是了解基因表达如何响应各种信号和应力。换句话说，了解细胞信号传导机制对于了解生活过程至关重要。这个建议侧重于哺乳动物细胞如何感知某些代谢产物并使用该信息来调节蛋白质功能。常见的细胞代谢产物，例如共酶A，谷胱甘肽和烟酰胺腺苷二核苷酸在各种代谢途径中的重要作用。许多蛋白质后翻译修饰也使用这些代谢物。因此，保持这些代谢产物的浓度至关重要。细胞和生物必须能够感知这些代谢产物并使用信息来调节生物过程。然而，对于这些代谢产物的感测机制知之甚少。在此Mira应用中，我将集中精力关于使用化学生物学技术来确定哺乳动物细胞如何感知常见代谢产物来调节蛋白质功能。初步结果表明，这是一个非常有趣且令人兴奋的领域，值得很多更多调查。这是我实验室的全新研究方向，与我以前的和HHMI支持的研究。拟议的研究将确定蛋白质的许多新型调节机制小分子代谢物的功能。反过来，这将更好地理解细胞信号和解决生物医学科学中最重要的挑战之一。这些监管机制还可以直接影响治疗剂的发展，因为它们将有助于发展变构蛋白质的抑制剂或活化剂。