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

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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.