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，而且对我们试图理解和减轻人类这些过程也很重要。生命史理论预测，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），即适度减少营养摄入，已被证明可以延长多种物种的寿命，减缓衰老速度。DR的这种延年益寿效应的进化解释是，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保守的，但最近的研究表明，DR的反应存在遗传变异。此外，最近的理论质疑DR的延年益寿和抗衰老作用是否会在生物体暴露于与生态相关的应激源（如病原体、物理损伤和温度变化）时持续存在。了解长寿和衰老对饮食反应的这种变化程度，对于提高我们对衰老过程的理解，饮食如何调节衰老过程，以及个体和环境之间的差异，显然是很重要的。本项目将以果蝇（Drosophila melanogaster）为模型生物，详细研究其对DR反应的遗传变异和暴露于环境胁迫下的影响。果蝇将在酵母含量不同的饮食中饲养，并评估这些饮食对不同性状的寿命、繁殖和衰老的影响。利用果蝇遗传参考小组（DGRP）（约200个果蝇自交系）进行定量遗传实验，以估计DR响应的定量遗传变异以及DR如何影响生活史性状之间的遗传（co）变异；这是衡量生命史权衡的关键指标。这些系的全基因组序列数据的存在将允许调查潜在这种变异的候选基因。此外，不同饮食的果蝇将暴露在包括病原体，物理伤害和温度变化在内的环境压力源中，以评估环境变化对dr反应的影响。该博士课程将提供设计，实施和分析多代复杂实验的培训，以及学习分析和分析生长，生存，身体性能等特征的技术。此外，黑腹果蝇代表了一个非常好的研究和灵活的系统，这将允许学生发展自己的想法。

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.