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Personal profile

Biography

I obtained a B.Sc. in Biochemistry (1986) and a Ph.D. in Biochemistry (1990) from the University of Kent (UK). I first studied the control and fidelity of protein synthesis in yeast as a graduate student under the supervision of Professor Mick Tuite (Kent, 1986-1990) and then as a Postdoc with Dr Alan Hinnebusch at NIH (Bethesda, USA, 1990-1994). My research into the responses of eukaryotic cells to oxidative stress conditions started whilst I was a Research Fellow in the laboratory of Professor Ian Dawes at the University of New South Wales (Sydney, 1994-1999). Since starting my own group at Manchester (1999), my research has been aimed at understanding the responses of eukaryotic cells to stress conditions, with a particular focus on oxidative stress.


 

Research interests

Our research efforts are aimed at understanding the responses of eukaryotic cells to oxidative stress using the yeast Saccharomyces cerevisiae as a model organism. All aerobic organisms are exposed to reactive oxygen species (ROS) during the course of normal aerobic metabolism or following exposure to radical-generating compounds. Such ROS can cause wide-ranging damage to cells and an oxidative stress is said to occur when the cellular survival mechanisms are unable to cope with the ROS or the damage caused by them. Oxidative damage is associated with various disease processes including cancer, ageing and neurodegenerative disorders, and is of particular concern to industry. Thus, understanding the causes of oxidative stress, and in turn, the molecular responses to such stress, is of fundamental importance.

We have characterized the activity and expression of yeast antioxidants and stress response molecules in order to obtain a global overview of the molecular events occurring in cells exposed to oxidative stress conditions. A major focus has been to characterize the role of sulphydryl regulation and we have defined the functional overlap between the thioredoxin and glutaredoxin systems, which are the major redox regulatory systems. This is important given the established links between defective thiol regulation and disease. More recently, we have demonstrated that the thioredoxin system can prevent protein aggregation and functions to protect against the oxidative stress associated with protein aggregates. This led to our recent finding that the Tsa1 peroxiredoxin suppresses the de novo formation of the [PSI+] prion in yeast. This is an important finding since the molecular basis by which mammalian and fungal prions arise spontaneously is poorly understood. We have analysed the changes in gene expression following oxidative stress, focussing on post-transcriptional control mechanisms. Our studies have shown that the response to oxidative stress is mediated by oxidant-specific regulation of translation initiation, emphasizing our current view that post-transcriptional controls are crucial mechanisms underlying the ability of all cells to adapt to stress conditions.

 

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Research Beacons, Institutes and Platforms

  • Manchester Institute for Collaborative Research on Ageing

Keywords

  • Yeast
  • protein synthesis
  • prion
  • Protein aggregation
  • redox biology
  • stress responses

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