I gained my PhD at the University of Edinburgh for research into the molecular mechanisms of synaptic vesicle recycling.  I then completed a post-doctoral position at the University of Sheffield with Prof. Liz Smythe, investigating membrane trafficking pathways before returning to work with Prof. Mike Cousin at the University of Edinburgh for two post-doctoral positions.  This work revealed that signalling cascades can regulate synaptic vesicle retrieval at the presynapse with potential implications for neuronal dysfunction.  I am currently a lecturer in the School of Biomedical Sciences and my research focuses on investigating presynaptic dysfunction in preclinical models of Huntington’s disease.

2001-2005 PhD Prof. M.Cousin Lab, University of Edinburgh

1997-2001 BSc (Hons) Biochemistry, University of Edinburgh

Centre for Discovery Brain Sciences

My research focuses on investigating the molecular mechanisms of neurodegeneration at the presynapse using Huntington’s Disease as a model.

Neurodegeneration can be caused by a failure of neurons to efficiently and accurately communicate with one another at structures called synapses and this is a hallmark of many conditions, including Huntington’s disease, Parkinson’s disease, Alzheimer’s disease and prion related diseases called synaptopathies.  By investigating the molecular mechanisms governing the early events leading to synaptic failure, we may be able to prevent or at least slow the progression of synaptic failure.  My research uses Huntington’s Disease as a model to examine this.

https://www.ed.ac.uk/discovery-brain-sciences/our-staff/research-groups/karen-smillie

Huntington’s disease (HD) is a late onset neurodegenerative disease with no known cure.  The main symptoms of this debilitating condition are uncontrolled writhing movements, cognitive decline and altered psychological behaviour.  These symptoms reflect neuronal death especially in the striatum and cortex of HD sufferers.  HD is an autosomal dominant inherited disorder caused by mutation of a single gene, huntingtin.  The unaffected version of the gene has 10-26 copies of the trinucleotide repeat CAG (coding for glutamine) and affected individuals have an expansion of this region with at least 40 copies.  The resulting huntingtin protein has an expanded stretch of polyglutamine residues altering the conformation, structure and binding properties of this protein, potentially leading to altered function and neuronal toxicity.   

My research uses a knock-in mouse model of HD (Q140) which expresses the expanded form of the huntingtin protein with approximately 140 repeats.  We culture hippocampal, striatal, cortical and cerebellar granule neurons from these mice and investigate the presynaptic mechanisms involved in neurotransmitter release and synaptic vesicle recycling.  We do this through biochemical assays, fluorescent imaging of real-time vesicle recycling and electron microscopy.  My research also uses induced pluripotent stem cells from patients with HD.  We are currently characterising these cells and will be using them in parallel with the mouse cultures to investigate presynaptic dysfunction in a human model of HD.  Together, the findings from these models will provide important insights into the cause of neuronal degeneration in this devastating condition and potentially provide information which is applicable to neurodegeneration more broadly.

Jessica Nicholson-Fish (2011 – 2016)

Hamish Runciman (2019 - current)

Prof. Mike Cousin (University of Edinburgh, UK)

Dr Lyndsay Murray (University of Edinburgh, UK)

Dr Sarah Gordon (Florey Institute of Neuroscience and Mental Health, Melbourne, Australia) 

Prof. Nick Allen (University of Cardiff, UK)

I teach on a range of courses from first year to postgraduate masters in the School of Biomedical Sciences and also contribute to courses in the School of Biological Sciences (listed below).  I am also the deputy Programme Organiser for Medical Sciences Honours and the deputy course organiser for Clinical Biochemistry and Endocrinology 3.  As well as serving on several course CAGs, I am a member of the Medical Sciences Board of Examiners.  I supervise Masters students for laboratory projects from mutiple programmes and am a Personal Tutor for Biomedical Sciences Undergraduate students.

Undergraduate

Year 1: Medical Sciences 1

Year 3: Clinical Biochemistry and Endocrinology 3

          (including responsibility for the Biomedical and Laboratory Sciences   students on this course)

Year 4: Honours Medical Sciences

              (including Medical Sciences 4 core course, portfolio course and dissertation course)

              Pharmacology 4

Postgraduate

MScR Integrative Neuroscience

MScR Biomedical Sciences (Life Sciences)

Other

The Dynamic Cell 2

Member of Medical Sciences Board of Examiners

Member of Senior Honours Medical Sciences management group

Member of Clinical Biochemistry and Endocrinology 3 Course Assessment Group

Member of The Dynamic Cell Course Assessment Group