Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
- Professor of Neurogenetics
- Neurodegenerative Diseases
- Institute of Neurology
- Faculty of Brain Sciences
I have an undergraduate degree (BA(Hons,), MA) from St Anne’s College, University of Oxford, in Physiological Sciences which I took between 1978 – 1981. In 1983 I started a PhD in mouse molecular genetics, the microdissection of the mouse X chromosome at St Mary’s Hospital Medical School (Imperial College). My primary supervisor was Professor Steve Brown and I undertook a considerable part of the PhD under the supervision of Dr Mary Lyon at MRC Harwell. This was a technically demanding project involving the dissection of individual chromosomes and cloning DNA fragments into plasmids, in nanolitre volumes. I completed the PhD in 1986 and in 1987 started my postdoctoral work with Professor David Page at the Whitehead Institute, MIT. I started working on a project to find the human male sex determining factor and then moved onto a project to identify genes involved in Turner syndrome. This turned into one of the early human positional cloning projects and resulted in several publications. In 1990 I returned to UK on a Royal Society Research Fellowship to start my independent lab at Imperial College, studying the effects of aneuploidy. In 1991 Victor Tybulewicz (at MRC NIMR) and I gained funding from the Wellcome Trust to start a long-term project to create a new ‘humanised’ mouse model of Down syndrome, which led to the research project we now pursue jointly to use mouse molecular genetics to find the individual dosage sensitive genes giving rise to aspects of Down syndrome. In parallel my lab has also created and analysed a series of mouse models with motor neuron degeneration, trying to shed light on why motor neurons die in the disease amyotrophic lateral sclerosis. These two research themes come together in an interest in mouse models in neurodegeneration.
In 2007 I was elected to become a Fellow of the Academy of Medical Sciences, in 2009 I became a Member of EMBO, and in 2010 I became a Fellow of the Society of Biology.
We are interested in learning more of the genetic basis of two disorders that involve neurodegeneration in humans: motor neuron diseases and Down syndrome. We work with the mouse as a genetic model of humans.
Motor neuron diseases (MNDs) are common and incurable, and arise when the motor neurons that extend from the brain into the spinal cord and out to the muscles, degenerate and die. Spinal muscular atrophy, one form of MND is the biggest single genetic killer of children, and amyotrophic lateral sclerosis (ALS) is an adult form of MND that arises in mid-life. Although single genes are known that cause MNDs, it is not clear how the mutant genes exert their effects or what other genes can modify the pathways involved. Many different cellular systems are affected, including the transport of vesicles, organelles, molecules, in the axon and cell body. We are particularly interested in one transport complex, dynein, which transports many different cargoes from the synapse to the cell body and which moves vesicles around in the cell body. We are looking at the effects of mutant dynein and how this relates to motor neuron cell death.
We are also working with mouse models of Down syndrome. Down syndrome is the most common known genetic form of mental retardation. Down syndrome commonly results in the histopathology of Alzheimerâ??s disease in the brain, in the mid-30s (although not necessarily behavioural changes). Some form of neurodegeneration may be taking place, and, interestingly, there are also changes in axonal transport in Down syndrome. We are characterizing our mouse models in order to look specifically at axonal transport, and then to try to work out which genes are responsible for any changes we find, as such genes are likely to be important for neurodegeneration in the general population.
I am graduate tutor for my Department which entails keeping an eye on the progress of, currently, >30 PhD and MD and MRes students. I send a questionnaire to all graduate students and their primary and secondary supervisors every six months to monitor progress and I see all new graduate students in January of the year they start. In addition I regularly meet with graduate students – and occasionally supervisors - at their request to discuss academic or other aspects of their PhDs. The questionnaire system also allows me to monitor supervisors and their approach to students.
Within my own research group, in addition to my own PhD students, I am secondary supervisor for a student from CRUK and two students from elsewhere within UCL and I am very active in meeting these students on a regular basis and being engaged in their PhDs. In addition I take rotation students from the UCL ION 4-year PhD course and Masters and undergradulate students from a variety of UCL courses, and, occasionally, outside courses.
I regularly undertake PhD vivas for UCL and external universities.
I have taught at Imperial (where I am a Visiting Professor) on a Masters course and at Kings, and have taught on the UCL ION Neuroscience Masters course.
I am also pastoral supervisor for students on the UCL ION Neuroscience masters course. I note that the MRC Prion Unit is developing a 4-year PhD course (driven by Professor Parmjit Jat) and I will monitor the progress of this course.
I sit on the UCL ION Neuroscience/Clinical Masters committee and on the Higher Degrees Sub-Committee for ION.
I am also the academic Mentor for a lecturer in my Department.
|01-OCT-2001 – 30-SEP-2020||Professor of Neurogenetics||Neurodegenerative Disease||UCL, United Kingdom|
|1986||PhD||Doctor of Philosophy – Genetics||Imperial College of Science, Technology and Medicine|
|1981||MA Oxon||MA Oxon – Physiological Science||University of Oxford|