Physiological and genetic mechanisms underlying variation in growth within species

在所有物种中，许多性状表现为个体之间的连续变异(例如，身体质量)，而不是离散的一种或另一种状态(例如，血型)。这些连续的性状是由环境和潜在的大量基因决定的。我研究计划的目标是了解物种内生长差异背后的生理和遗传因素。我将通过研究特定的生理途径，并将生理变化与身体大小的变化(例如，质量、骨骼长度、体重)联系起来，来实现这一点。等)。我的计划的重点将是健康个体之间自然发生的变异，而不是人工遗传修饰的影响。到目前为止，这一领域的大量工作已经研究了近交系小鼠。尽管近交系动物从遗传角度提供了优势，但尚不清楚它们在现实世界中的代表性有多大。因此，我将在实验室研究近交系和近交系小鼠种群，然后利用这项工作产生假说，我将在自然啮齿动物种群中进行测试。这将把遗传和生理结果置于生态环境中(例如，遗传和生理变化对动物的生存和繁殖能力有什么影响？)。此外，我的研究将深入了解遗传变异与整个动物特征(如体型)的变异相关的途径。这些信息对于理解为什么有些人比其他人更容易患某种疾病至关重要。例如，我打算研究的生理途径之一会影响骨密度，因此这条途径的变异可能会影响对骨质疏松症的易感性。了解物种内变异的机制对于预测自然种群将如何应对不断变化的环境也很重要，因为基因变异是实现适应的原材料。

Within all species, many traits show continuous variation between individuals (e.g., body mass) rather than discrete one-or-the-other states (e.g., blood type).  Continuous traits are determined by both the environment and a potentially large number of genes.  The goal of my research programme is to understand the physiological and genetic factors underlying within-species variation in growth.  I will achieve this by studying specific physiological pathways and relating physiological variation to variation in body size (e.g., mass, bone length, etc) in mice.  The focus of my programme will be on naturally-occurring variation among healthy individuals, and not on the effects of artificial genetic modifications.      A great deal of work in this field has examined inbred mice.  Although inbred animals offer advantages from a genetic perspective, it is not clear how representative they are of the 'real world'.  I will therefore study both inbred and outbred populations of mice in the laboratory, and then use this work to generate hypotheses which I will test in natural populations of rodents.  This will put the genetic and physiological results in an ecological context (e.g., what are the consequences of genetic and physiological variation for an animal's ability to survive and reproduce?).      My research will yield insight into the pathways through which genetic variation is related to variation in whole-animal traits such as body size.  Such information is crucial to understanding why some people are more susceptible to a particular disease than others.  For example, one of the physiological pathways I intend to study influences bone mineral density, and so variation in this pathway may affect susceptibility to osteoporosis.  Understanding the mechanisms responsible for within-species variation is also important to predicting how natural populations will respond to a changing environment, since genetic variation is the raw material by which adaptation may be achieved.