The genetic basis of the long-term maintenance of muscle function in animals.

我研究的总体目标是了解组织是如何形成的，以及一旦它们形成，它们如何在生物体的整个生命过程中保持其组织。特别是我的实验室利用遗传方法来剖析各种机制，确保组织能够保持其结构，从而保持其在整个生命周期中发挥作用的能力。肌肉细胞在这方面特别有趣，因为它们在结构上高度组织化，并且寿命相对较长，这意味着它们长时间保持其结构完整性。这是值得注意的，因为肌肉承受巨大的机械负荷，因为经历放松和收缩的周期。我提议的NSERC资助的研究项目将调查肌肉细胞如何能够在持续的机械应力下在生物体的整个生命过程中保持其组织和功能。 我们的实验室使用苍蝇肌肉进行我们的实验，因为它们提供了一个优秀的，遗传上易于处理的体内模型系统，以研究整个生物体中的肌肉维护。果蝇的成年肌肉组织在果蝇寿命期间保持，通常为4-6周，在此期间不产生额外的肌肉细胞。我们研究的一个关键目标是利用遗传学来识别参与肌肉组织维护的基因。以前，实现这一目标的主要障碍是，完全废除参与肌肉维持的基因通常会干扰胚胎中肌肉的形成。我们最近开发了一种方法，通过使用新的遗传工具来规避这个问题。我们已经使用这种方法结合测量成人肌肉功能的测定来筛选肌肉组织维持所需的基因。我们确定了30多个基因，这些基因对维持成人肌肉的肌肉功能至关重要。 我的NSERC申请详细介绍了一组实验，旨在从机理上全面了解我们筛选出的基因如何促进肌肉组织的维持。

The overall goal of my research is to understand how tissues form and once they form how they maintain their organization throughout the life of the organism. In particular my lab utilizes genetic approaches to dissect various mechanism ensure tissues are able to maintain their structure and thus their ability to function throughout life. Muscle cells are particularly interesting in this regard because they are both highly organized structurally and relatively long lived, meaning that they sustain their structural integrity for a long time. This is remarkable because muscle withstand enormous mechanical loads as the undergo cycles of relaxation and contraction. The NSERC funded research program I propose will investigate the how muscle cells are able to maintain their organization and function throughout the life of the organism while under sustained mechanical strain. Our lab uses fly muscles for our experiments since they provide an excellent, genetically tractable, in vivo model system to study muscle maintenance in the context of the whole organism. The adult musculuature of the fly is maintained for the duration of fly life, typically 4-6 weeks during during which no additional muscle cells are made. A key aim of our research is to use genetics to identify genes that are involved in muscle tissue maintenance. Previously, the main obstacle in achieving this goal has been that the complete abolition of genes that are involved in muscle maintenance often interferes with the formation of muscles in the embryo. We have recently developed a way to circumvent this problem by using novel genetic tools. We have used this approach coupled with assays that measure muscle function in the adult to screen for genes that are required for muscle tissue maintenance. We identified over 3 dozen genes that are essential to maintain muscle function in the adult muscles. My NSERC application details a set of experiments designed to obtain a thorough mechanistic understanding of how the genes identified in our screen contribute to muscle tissue maintenance.