Public engagement and science policy
In addition to my research activities, I believe passionately in the importance of communicating the wonder and relevance of scientific advances as broadly as possible. I am privileged to have been awarded two Vice Chancellor's Awards for Public Engagement in recognition of my work in this area, and to have been invited to give a TEDx talk as part of TEDx Whitehall 2018. I have previously spoken at Cheltenham Science Festival and Hay Festival, and have run multiple public engagement events including as part of the Science Museum Lates and Royal Society Summer Exhibition Twilight programmes.
Currently, I am working with Eleanor Minney, a talented Oxford-based artist, inspired by my research. As part of our collaboration, we have developed Switching Perceptions, an award-winning project that uses art as a means to facilitate dialogue about the experience of and causes of psychiatric illnesses. We have exhibited Switching Perceptions at the Bethlem Gallery and the Barbican. We are grateful to the Royal Society and the University of Oxford for funding our collaboration and to the Bethlem Gallery and National Psychosis Unit for supporting Switching Perceptions.
I am active in the area of science policy. As well as giving talks to policy makers about my area of research (including at HM Treasury and TEDx Whitehall), I am also a Fellow of the Westminster Abbey Institute and serve on the Royal Society's Science Policy Expert Advisory Committee
B.Sc. M.Sc. D.Phil.
- Associate Professor
- Supernumerary Fellow, University College
Understanding links between genes and brain dysfunction to find new drug targets for psychiatric disorders
Our current research
My group's research investigates how individual genes affect the complex brain functions that are altered in psychiatric disorders in order to identify new drug targets.
We use a wide range of experimental techniques to study the function of these genes at all levels - from individual cells to the whole person. To achieve this, we collaborate with many other researchers within Oxford, elsewhere in the UK, and internationally.
Our current research focuses on two main areas: the voltage-gated calcium channels (VGCCs) and the KALRN gene.
In recent years, large-scale studies have identified regions of the genome that are associated with risk for psychiatric disorders. The VGCC and KALRN genes have emerged from these (and other) studies, as promising new drug targets for treating psychiatric illnesses. As well as understanding how KALRN and the VGCCs influence brain function and risk for psychiatric illness, we are investigating which VGCC and KALRN subtypes are expressed in the brain compared with peripheral tissues, since brain subtypes are likely to represent the most selective drug targets.
From gene to drug target: the COMT story
My early research provides an example of the type of multidisciplinary and collaborative research needed to translate genetic understanding into novel therapeutic targets.
Patients with schizophrenia experience problems with cognitive function (memory and attention) that are not helped by current treatments. Working with my collaborators over many years, my research suggests that inhibiting the COMT enzyme may be a new way of treating this cognitive dysfunction. As a result of this research, new COMT inhibitors are now being trialled in patients with schizophrenia.
COMT (catechol-O-methyltransferase) is an enzyme that breaks down dopamine. The COMT gene contains a common variant that encodes high or low activity forms of the enzyme. We and many others have used neuroimaging approaches to show that COMT plays a particularly important role in the human frontal cortex, a brain region which is crucial to cognitive function and in which dopamine plays an important role. We showed that inhibiting COMT increases dopamine levels in the frontal cortex and improves memory and attention. We demonstrated in both humans and mice that this beneficial effect of COMT inhibition is maximal in individuals with genetically-encoded high COMT activity, i.e. low dopamine. Together, these data suggest that COMT inhibition enhances cognitive function by increasing dopamine signalling in the frontal cortex, and therefore that this pharmacological approach may be useful for treating cognitive dysfunction in individuals with reduced frontal dopamine, including those with schizophrenia.
Clark MB. et al, (2019), Mol Psychiatry
Induced pluripotent stem cells in psychiatry: an overview and critical perspective
De Los Angeles A. et al, (2021), Biological Psychiatry
Tunbridge EM. et al, (2019), Biol Psychiatry, 86, 608 - 620
Farrell SM. et al, (2012), Biol Psychiatry, 71, 538 - 544
Tunbridge EM. et al, (2006), Biol Psychiatry, 60, 141 - 151