Integrative Biology of Insect Muscle: Molecular Through Ecological Investigations of Locomotor Performance

9600840马登这项研究通过细胞、生物和生态水平在分子水平上调查模式生物的运动生理学，并将演示一个水平上的影响如何与其他水平上的影响相互作用。通过这样做，这项研究将导致对支配肌肉表现生理学的机制和进化过程的新理解。在成虫成熟的过程中，蜻蜓(Libelula Pulchella)的飞行性能和肌肉功能的温度敏感度发生了巨大的变化。初步数据表明，这种发育转变背后的机制是肌肉激活对钙的敏感性增加了10倍，这似乎是由于钙调节蛋白肌钙蛋白-t的异构体表达的变化引起的。研究人员将使用重组肌钙蛋白-t进行异构体提取/替换实验，实验将展示特定年龄的肌钙蛋白-t异构体在确定肌肉激活的钙敏感性方面所起的作用。这些实验将提供一些解决肌钙蛋白-t异构体变异的特定细胞作用的第一批数据。肌钙蛋白-t亚型的变化发生在许多类型的动物(包括人类)的肌肉发育过程中，以及在心脏骤停和心脏骤停后恢复的人类心肌中。肌钙蛋白-t的突变导致人类遗传性心脏病(肥厚型心肌病)，其机制目前尚不清楚。因此，这一结果将具有普遍和潜在的临床价值。初步数据还表明，肌肉激活的钙敏感性的变化影响肌肉抽搐收缩的时间和力量产生，进而可能导致运动能量效率的变化。研究人员将通过确定飞行能量效率如何随年龄和肌肉成熟而变化来验证这一预测。他们将对表现出相似和不同肌肉成熟模式的远亲蜻蜓进行平行实验，以确定结果是否可以进行准确的预测，并将其推广到其他物种。

9600840 Marden This research investigates the locomotor physiology of a model organism at molecular through cellular, organismal, and ecological levels, and will demonstrate how effects at one level interact with effects at other levels. In so doing, the research would lead to a novel understanding of mechanistic and evolutionary processes that govern performance physiology of muscle. Dragonflies (Libellula pulchella) undergo a dramatic change in flight performance and thermal sensitivity of muscle function during adult maturation. Preliminary data suggest that the mechanism underlying this developmental transition is a tenfold increase in calcium sensitivity of muscle activation, which appears to be caused by a change in isoform expression of the calcium regulatory protein troponin-t. The investigators will use recombinant troponin-t to perform isoform extraction/replacement experiments that will experimentally demonstrate the role that age-specific troponin-t isoforms play in determining calcium sensitivity of muscle activation. These experiments will provide some of the first data that address the specific cellular role of troponin-t isoform variation. Troponin-t isoform shifts occur during muscle development in many types of animals (including humans), as well as human heart muscle during cardiac arrest and recovery from cardiac arrest. Mutations in troponin-t cause, by mechanisms presently unknown, an inherited heart disease in humans (hypertrophic cardiac myopathy). Thus, the results will have general andpotentially even clinical value. Preliminary data also indicate that changes in calcium sensitivity of muscle activation affect the timing and force generation of muscle twitch contractions, which in turn may cause changes in the energy efficiency of locomotion. The researchers will test this prediction by determ ining how energy efficiency of flight varies with age and muscle maturation. They will perform parallel experiments with distantly related dragonflies that show similar and dissimilar patterns of muscle maturation in order to determine if the results allow accurate predictions that can be extended to other species.