Personal profile

Biography

I am a Senior Lecturer and research group leader in the Faculty of Life Sciences.  I obtained a B.Sc (Hons) in Biochemistry and a Ph.D in Molecular Biology from the University of Sheffield. I performed my post-doctoral research in the USA in the laboratory of Professor Roger Davis at UMASS Medical Center. I was appointed as a Research Assistant Professor at UMASS Medical Center in 1997 and moved to the University of Manchester as a lecturer in 2000. I was awarded a Lister Institute Jenner Research Fellowship in 2001 and became a Senior Lecturer in 2010. I am currently Postgraduate Research Director for the School of Biological Sciences. 

 

Research interests

Regulation of stress-responses and ageing by mitochondria-to-nuclear signalling (in collaboration with Gino Poulin’s group)

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. Our research has uncovered a novel evolutionarily conserved route of communication between mitochondria and nuclei that is sensitive to reactive oxygen species and regulates the expression of stress-response genes. Furthermore, perturbation of this pathway modulates lifespan in both C. elegans and mice. We are investigating how changes in the transcriptional network in response to mitochondrial signalling controls ageing and also determining the molecular mechanisms underlying ROS-mediated regulation of this pathway. This research will enhance our understanding of how perturbation of mitochondrial communication with nuclei contributes to ageing and ageing-related diseases.

Determination of cell fate by regulators of the TOR signalling pathway

To survive and grow, cells and organisms must coordinate their metabolism with changes in their environment. The TOR signalling pathway is a master regulator of metabolism and growth that responds to growth factors, stress and nutrients. It is implicated in diseases including cancer, diabetes, and obesity, making it an attractive target for therapeutic intervention. The TOR protein kinase is at the centre of a network and forms two discrete complexes (TORC1 and TORC2) that are differentially regulated and target distinct sets of substrates. We have identified novel regulators of TOR signaling and we are currently characterising how these proteins modulate specific TOR functions, including cell size and the cell cycle. This work will contribute to our understanding of how a key signalling pathway integrates multiple signals to direct cellular responses that maintain homeostasis, the breakdown of which can lead to disease.

Regulation of neuronal fate by the JIP1 scaffold protein

Neuronal development and survival are controlled by a network of interacting signalling pathways. The JNK MAP kinase pathway has been strongly implicated in both processes. JNK pathway activity and localisation can be regulated by the JNK-interacting protein (JIP) family of scaffold proteins. JIP proteins also associate with other protein kinases, kinesin motor proteins, amyloid precursor protein, cell surface receptors and transcriptional regulatory proteins. These multiple interactions suggest that JIPs can integrate many signalling pathways. We have uncovered an important role for JIP1 in neuronal development. However, JIP1 also promotes JNK-mediated apoptosis and has been implicated in Alzheimer’s disease and stroke.  We are investigating these dual roles of JIP1 with particular focus on how it integrates diverse signals and directs changes in neurone morphology and gene expression. We are also interested in the role of JIP1/JNK in nerve regeneration following injury. Our research provides novel insights into how signalling mechanisms direct neurone behaviour and will contribute to the design of appropriate therapies to combat brain injury and disease.

Overview

The research in my laboratory addresses how cells respond to their environment. In particular, we focus on signalling pathways that are regulated by stresses that include physical injury, changes in oxygen levels or temperature, radiation and infection or disease. These stress-induced pathways mitigate the effects of stress in order to maintain cell function. They predominantly do this by regulating the expression of genes in the cell nucleus that promote a protective response. However, high levels of stress can result in cell death and checkpoints exist to determine whether a cell can be repaired or whether it dies. Impairment of these checkpoints or disruption of stress signaling pathways can lead to developmental abnormities and diseases such as cancer, diabetes and neurodegeneration. Furthermore, there is increasing evidence that stress-response pathways play a major role in controlling ageing and lifespan. Current projects include (1) understanding how mitochondria communicate with the nucleus in response to reactive oxygen species and how this impacts on ageing, (2) elucidating mechanisms governing the regulation of TOR, a central mediator of cell fate, and (3) determining the cellular function of an integrator of stress signaling in neurones that is implicated in stroke and neurodegenerative disease.

Teaching

I coordinate and lecture on the final year undergraduate Cell Signalling unit. I also contribute to undergraduate tutorials and Problem Based Learning (PBL) tutorials for medical students.

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

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