A brief history: I graduated with a PhD in molecular cell biology at the University of Melbourne (Australia) in 1994, and pursed subsequent postdoctoral positions at St Andrews University and University College London (UCL) in the UK, followed by an independent Wellcome Trust Career Development fellowship at UCL. I moved to Royal Holloway University of London in 2006, where I am now Professor of Molecular Cell Biology and have been the Head of the Centre for Biomedical Sciences for 12 years, and I continue my research into areas of molecular cell biology, neuroscience, pharmacology, drug development, and pharmacogenetics through studies often using the social amoeba Dictyostelium, and then translating discoveries to relevant mammalian models.
Our research interests: I have a long-standing drive to improve the quality of life for people in our society, through better understanding the cellular basis of disease and by developing new therapeutic treatments. I often undertake an innovative approach for my research, by primarily employing a simple non-animal model for early stage research, called the social amoeba Dictyostelium (see here and imaged below), which allows a range of experiments not available using traditional (mammalian) models. Using this model provides both specific advantages in research, and contributes to developing animal replacement, reduction and refinement (3Rs) research approaches (see here).
Some central areas of my research are listed here:
Can we develop better treatments for Epilepsy: We have employed Dictyostelium as an advantageous model system to examine how treatments for epilepsy work at a cellular level (here, here, and here, and below image). We have then been able to identify new chemicals that may provide better or safer treatments for epilepsy using mammalian models. This long term project has been in close collaboration with Prof Matthew Walker (here), and with the US government agency (ETSP) (here). Highlights of this work include identifying how Valproic acid (valproate, Depakote, depakene) works in Dictyostelium (here, here, and here) and in the brain (here), leading to the identification of potential novel treatments for epilepsy (here, here, and here). Through this work, we have also identified a likely mechanism of a diet used in the treatment of drug resistant epilepsy in children, called the MCT ketogenic diet (here, here, here, here andhere). This advance is likely to have far-reaching effects on the field of drug resistant epilepsy research and ultimately patient treatment.
Key collaborators: Prof Matthew Walker (here)
Key industry partners: Vitaflo Ltd (here)
Evolutionary origins of the proteins involved in disease: Many proteins are highly conserved throughout evolution across distant species, suggesting key roles in cells that have been retained. Our group has investigated the conservation of function of several proteins, from our amoeba model to humans. The importance of this is two-fold: firstly, through establishing a conserved function of proteins across a million years of evolution, we provide evidence for essential function of that protein. Secondly, a conserved function enables us to investigate the role of the protein in cell function, or as a target for therapeutic drugs or natural products. Our research in this area has included several studies on a key group of proteins involved in Alzheimer’s disease (called the gamma secretase complex), where we have established a conserved cell function between Dictyostelium and human proteins (here, here, here), and identified roles of these proteins that may be involved in the damage caused in Alzheimer’s disease. Other conserved proteins include targets for bitter tasting chemicals (here).
Key collaborators: Dr Richard Killick, Prof Alan Kimmel
What cellular mechanisms underlie the basis of Bipolar disorder and its treatment: Bipolar disorder is a severe neuropsychiatric disorder that is treated with several drug that are also effective in the epilepsy (including lithium, valproic acid, carbamazepine). Our research has examined how these treatments function in cells, both in Dictyostelium and in mammalian neurons. We have provided key evidence to support a theory of bipolar disorder treatment (here, here, here), and new mechanism (here) and recently suggested a molecular target for this mechanism (here).
Natural products, medicines, and pharmacogenetics: Chemicals derived from plants provide an enormous potential for use as medical treatments. These chemicals include products commonly found in fruits (e.g. flavonoids) and thought to work as anti-oxidants, and products found in flowers or buds (e.g. cannabis)(below). We have used Dictyostelium to analyse many natural products to improve our understanding of how they may function in health and disease (here). Products include the flavonoids such as naringenin (here), food additives such as curcumin found in turmeric (here), cannabinoids used in medicine and others. By using Dictyostelium, we can identifying genes that control the function of these compounds, and from this help to describe how the compounds may function in maintaining good health or treating disease such as polycystic kidney disease (here), or cancer (here).