Genetic and environmental variation in the effect of dietary restriction on life-history trade-offs and ageing in Drosophila

了解寿命和衰老变化的原因和后果不仅在生命史进化的背景下很重要，而且在我们试图理解和缓解人类的这些过程中也是重要的。生活史理论预测，寿命和衰老的变化与生存和繁殖之间的权衡有关。饮食限制(DR)是一种适度减少营养摄入量的方法，已被证明可以延长寿命，减缓各种物种的衰老速度。对DR这种延长寿命效应的进化解释是，它改变了生存和繁殖之间的权衡，有利于增加对生存的投资。虽然DR的作用被认为是进化上保守的，但最近的研究表明，DR的反应存在遗传差异。此外，最近的理论质疑，当生物体暴露在与生态相关的应激因素(如病原体、身体损伤和温度变化)时，DR的延长和抗衰老作用是否会持续下去。了解长寿和衰老对饮食的反应的这种差异的程度，对于提高我们对衰老过程的理解，饮食如何调节衰老，以及个人和环境之间的差异，显然是重要的。该项目将以黑腹果蝇作为模式生物，详细研究果蝇对DR反应的遗传变异以及暴露在环境压力下的影响。果蝇将被饲养在不同酵母含量的饲料中，并将评估这些饲料对各种性状的寿命、繁殖和衰老的影响。利用果蝇遗传参考小组(DGRP)(约200个果蝇近交系)，将进行定量遗传实验，以估计对DR的反应中的数量遗传变异，以及DR如何影响生活史性状之间的遗传(Co)变异，这是衡量生活史权衡的关键指标。这些品系的全基因组序列数据的存在将使研究这种变异的候选基因成为可能。此外，不同饮食的果蝇将暴露在包括病原体、身体损伤和温度变化在内的环境应激源中，以评估环境变化对Dr.的反应的影响。这个博士学位将提供跨多代复杂实验的设计、实施和分析方面的培训，以及分析和分析特征(如生长、存活、身体表现等)的学习技术。

Understanding the causes and consequences of variation in longevity and ageing is important not only in the context of life history evolution, but also in our attempts to understand and mitigate these processes in humans. Life history theory predicts that variation in longevity and ageing is related to the trade-off between survival and reproduction. Dietary restriction (DR), a modest reduction in nutrient intake, has been shown to increase longevity and slow rates of ageing across a diverse range of species. The evolutionary explanation for this prolongevity effect of DR is that it alters the trade-off between survival and reproduction in the favour of increased investment in survival. Although the effect of DR is thought to be evolutionarily conserved, recent studies suggest genetic variation in the response to DR. In addition, recent theory has questioned whether the prolongevity and anti-ageing effect of DR will persist when organisms are exposed to ecologically relevant stressors such as pathogens, physical injury and temperature variation. Understanding the extent of this variation in the response of longevity and ageing to diet is clearly important in improving our understanding of the ageing process, how it might be mediated by diet and how this may vary between individuals and environments. This project will use Drosophila melanogaster as a model organism in which to provide detailed studies of genetic variation in the response to DR and the effect of exposure to environmental stress.Drosophila will be reared on diets that differ in yeast content and the effect of these diets on longevity, reproduction and ageing in various traits will be assessed. Using the Drosophila Genetic Reference Panel (DGRP) (~ 200 inbred lines of Drosophila), quantitative genetic experiments will be performed to allow estimation of the quantitative genetic variation in the response to DR and how DR influences the genetic (co)variation between life history traits; a key measure of life history trade-offs. The existence of genome wide sequence data for these lines will allow investigation of candidate genes underlying this variation. In addition, Drosophila on different diets will be exposed to environmental stressors including pathogens, physical injury and temperature variation to assess the effect of environmental variation on the response to DR. This PhD will provide training in the design, implementation and analysis of complex experiments across multiple generations as well as learning techniques for assaying and analysing traits such as growth, survival, physical performance etc. In addition, Drosophila melanogaster represent an incredibly well studied and flexible system that will allow a student scope to develop their own ideas.