Regulation of stress-responses and ageing
Dr A J Whitmarsh
Dr G Poulin
Applications accepted all year round
Self-Funded PhD Students Only
Ageing occurs by the accumulation of damage to cells leading to progressive deterioration of physiological functions. It is influenced by both genetic and environmental factors. Importantly, genetic manipulations that slow ageing can also delay the onset of many diseases such as cancer and those associated with neuronal and muscle degeneration. Therefore, targeting the molecular basis of ageing may also protect from ageing-related disease. The signalling pathways that regulate lifespan are often associated with the cellular response to stress or nutrients. Mitochondrial function is sensitive to both and mutations in a number of genes encoding mitochondrial proteins affect lifespan. Mitochondria are a major source of reactive oxygen species (ROS) that are by-products of the electron transport chain. ROS can cause damage to cells so it is important for mitochondria to communicate effectively with the nucleus to promote protective responses and maintain homeostasis. Our research has uncovered a novel route of communication between mitochondria and nuclei that is sensitive to ROS and regulates the transcription of stress-response genes in both the model organism C. elegans and in human cells. Furthermore, perturbation of this pathway modulates lifespan in both C. elegans and mice. Projects are available to investigate how this novel pathway regulates transcriptional responses and contributes to ageing and ageing-related diseases. Approaches used will include cell culture, C. elegans transgenics, recombinant protein expression, mutagenesis, qPCR, immunoblotting and immunoprecipitation, fluorescence microscopy, RNAi, CRISPR gene editing and genomics.
This project has a Band 2 fee. Details of our different fee bands can be found on our website. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website. Informal enquiries may be made directly to the primary supervisor.
1. Kenyon, CJ (2010) Nature 464: 504-12.
2. Kourtis, N. and Tavernarkis, N. (2011) EMBO J. 30:2520-31.
3. Kotiadis, VN. et al., (2014) Biochim Biophys Acta 1840: 1254-65.