Sources transmission and effects of transcriptional noise in C. elegans ageing

衰老是一个受环境、基因和随机因素影响的可变过程。影响寿命和衰老的几个基因的活性受到环境的影响。该项目的目标是确定(1)是什么导致这些基因活性水平的波动，以及(2)基因活性波动与寿命和衰老的可变性之间的关系。在许多物种中，相似的基因和环境因素以相似的方式导致衰老。此外，由于物理规律，基因活动的可变性是一种普遍现象。因此，对蛔虫等简单动物的研究可以提供与包括人类在内的许多物种相关的这些过程的一般见解。我们将在蛔虫中使用强大的实验工具来剖析影响寿命和衰老的基因活动波动的原因，并弄清这些波动如何与寿命和衰老的变化有关。在老鼠或人类等其他动物身上进行这些实验将是非常困难和昂贵的。作为一种实验系统，蛔虫在对包括人类衰老在内的许多生物过程提供洞察方面有着既定的记录。我们将首先测量基因活性的波动，对这些波动的来源进行分类，并确定这些波动是如何受到食物和温度的影响的。由于这些基因在神经系统中相互交流，我们接下来将测试交流过程如何影响波动。最后，我们将确定基因活动的波动是否会导致衰老的变异性。为了获得这项工作所需的大量数据，我们将设计新的计算机化显微镜系统，能够以比人工工作快约50倍的速度收集数据，以及其他测量肌肉随年龄下降的工具。总之，这项研究将揭示基因活动的波动是如何产生并影响衰老和寿命的。

Ageing is a variable process affected by the environment, genes and random chance. The activity of several genes that affect lifespan and ageing are affected by the environment. The goal of this project is determine (1) what leads to fluctuations in the activity level of these genes and (2) the relationship between fluctuations in gene activity and variability in lifespan and ageing. In many species, similar genes and environmental factors contribute to ageing in similar ways. Moreover, variability in gene activity is a universal phenomenon, due to physical laws. Thus research in simple animals such as roundworms can provide general insights on these processes relevant to many species, including humans. We will use powerful experimental tools in the roundworm to dissect the causes of fluctuations in the activity of genes that affect lifespan and ageing, and discern how these fluctuations are linked to variation in lifespan and ageing. These experiments would be very difficult and expensive in other animals such as mice or humans. As an experimental system, roundworms have an established track record of providing insights to many biological processes, including human ageing. We will first measure the fluctuations in gene activity, classify the sources of these fluctuations and determine how these fluctuations are affected by food and temperature. Because these genes communicate with each other in the nervous system, we will next test how the communication process affects the fluctuations. Finally, we will determine whether fluctuations in gene activity lead to variability in ageing. To obtain the large amount of data needed for this work, we will engineer new computerised microscopy systems capable of collecting data ~50x faster than manual work by humans, and other tools to measure muscle decline with age. Together, this research will reveal how fluctuations in gene activity originate and affect ageing and lifespan.