Transcriptional and epigenetic control of skeletal muscle mass

自噬是一种蛋白质分解途径，线粒体等细胞器可以被运送到溶酶体进行循环利用。最近的研究，包括我们的研究，已经证明了自噬对于维持骨骼肌质量和功能的重要性。在过去的五年里，在NSERC的资助下，我在麦吉尔大学建立了一个前沿研究项目，致力于研究自噬在调节骨骼肌质量和功能中的重要性。这一计划的结果是在高评价的期刊上发表了七篇文章，并成功地培训了几名研究生和本科生。该程序还揭示了骨骼肌中的自噬持续数天，这需要通过转录和表观遗传网络长期上调自噬相关基因的表达。人们对这些网络的性质知之甚少。为了填补这一基础细胞生物学知识的空白，我想建立一个研究计划，重点确定转录因子EB(TFEB)、信号转导和转录激活因子1(STAT1)以及微RNAs(MiRNAs)在调节骨骼肌自噬中的作用。这一计划将是

Autophagy is a proteolytic pathway whereby organelles such as mitochondria can be delivered to the lysosome for recycling. Recent studies including ours have demonstrated the importance of autophagy to the maintenance of skeletal muscle mass and function. Over the past five years, with funding from NSERC, I established a leading-edge research program at McGill University dedicated to study the importance of autophagy in the regulation of skeletal muscle mass and function. This program resulted in the publication of seven articles in highly-rated journals and in the successful training of several graduate and undergraduate students. This program also revealed that autophagy in skeletal muscles persists for days and that this requires prolonged upregulation of autophagy-related gene expression by transcriptional and epigenetic networks. Little is known about the nature of these networks. To fill this gap in basic cell biology knowledge, I would like to establish a research program that focuses on identifying the roles of transcription factor EB (TFEB) and signal transducer and activator of transcription 1 (STAT1) as well as micro RNAs (miRNAs) in the regulation of skeletal muscle autophagy. This program would be an essential element in