About the symposium
Epilepsy, migraine and related paroxysmal neurological disorders affect over 15% of the population, and account for an enormous burden to the individual and to society. Progress in managing these diseases is slow, with many patients failing to respond to available medication. Understanding the mechanisms will be an essential step not only towards improved diagnosis, but also towards the development of rational therapies.
Epilepsy and migraine both exhibit strong heritability. Mendelian inheritance is however very uncommon, and only a few genes have been identified in the rare families where monogenic inheritance can be demonstrated. These genes overwhelmingly point to disorders of synaptic transmission. Polygenic variability of synaptic genes is highly likely to contribute to common sporadic forms of these diseases.
This proposal brings together complementary expertise in (i) clinical genetics and deep phenotyping of people affected by epilepsy, migraine and paroxysmal movement disorders, (ii) biophysics of presynaptic vesicle trafficking and exocytosis, (iii) the interaction of postsynaptic receptors, ion channels and perisynaptic neurotransmitter transporters, and (iv) vertebrate, invertebrate and human-derived cellular models of synaptic disorders.
Programme
8.25 Registration, coffee
9.00 Dimitri Kullmann (UCL-IoN): Introduction
Session 1
9.05 (Chair: Henry Houlden)
9.05 John Hardy (UCL-IoN) “Genomics of neurodegeneration”
9.40 Michael Johnson (Imperial) “Systems genetics discovery of
neurodevelopmental pathways “
10.15 Vincenzo Salpietro (UCL-IoN) “Genetic analysis of paroxysmal disorders”
10.40 Coffee
Session 2
11.10 (Chair: Stephanie Schorge)
11.10 David Bennett (Oxford) “Regulation of excitability within the somatosensory
system by CASPR2”
11.45 Shyam Krishnakumar (Yale): “Delineating the function of PRRT2 and its
role in paroxysmal neurological disorders”
12.20 Mala Shah (UCL) “Axonal and synaptic KV7/KCNQ channel function and
modulation”
12.55 Lunch & Posters
Session 3
14.00 (Chair: James Jepson)
14.00 Frank Hirth (King’s) "Mechanisms of G4C2/TDP-43 induced synaptopathy in a
Drosophila model of ALS/FTD”
14.35 Kofan Chen (UCL-IoN) “Mapping a genetic network underlying myoclonus dystonia
using Drosophila”
15.00 Beatriz Rico (King’s) "GABAergic circuitry assembly and schizophrenia"
15.35 Tea
Session 4
16.00 (Chair: Sanjay Sisodiya)
16.00 Pat Nolan (Harwell) “Investigating sleep and behavioural disturbances in a mouse
SNARE protein mutant”
16.35 Gabriele Lignani (UCL-IoN) “Increasing endogenous gene promoter efficiency as a
strategy to correct haploinsufficiency in epilepsy”
17.00 Holger Lerche (Tübingen) “Precision medicine in genetic epilepsies”
17.35 Reception
The symposium offers the opportunity to present research posters. Please submit an abstract by 16 September. Priority will be given to posters that report original research using cellular, molecular, genetic and circuit methods relevant to neurological and psychiatric disorders. Poster submitters will be notified by 23 September to confirm whether their abstracts have been accepted.
Abstracts should be structured as follows:
Title
Authors and affiliations
Abstract (200 words)
Abstracts to be sent to: Juliet.solomon@ucl.ac.uk
Supported by the Wellcome Trust through a Strategic Award on Synaptopathies
www.ucl.ac.uk/ion/synaptopathies
Speakers
Professor Michael Johnson
Professor Michael Johnson is Professor of Genomic Medicine and Clinical Neurology, and Deputy Head of the Centre for Clinical Translation in the Division of Brain Sciences at Imperial College London. His research is focussed on the use of network systems genetics to inform pathophysiological pathways and new drug therapies.
Dr. Ko-Fan Chen
Dr Ko-Fan Chen completed his degrees in Taiwan (1998-2005) before he studied his PhD with Ralf Stanewsky at Queen Mary, University of London using the model organism Drosophila to identify novel molecular mechanisms underlying circadian behaviours (2007-2011). Ko-Fan then joined Damian Crowther at University of Cambridge as a postdoctoral research associate to investigate the neuronal and molecular mechanisms underlying circadian abnormalities in Alzheimer’s disease (2012-2015). Here, Ko-Fan was first to demonstrate that the molecular circadian clock remains intact in the face of behavioural arrhythmia in a Drosophila Alzheimer’s model. Since joining James Jepson at the UCL Institute of Neurology in 2015, Ko-Fan has continued his interest in disease modelling and investigated the genetic network underlying myoclonus dystonia.
Prof. Dr. Holger Lerche, MD
Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research,
University of Tübingen, Tübingen, Germany
Prof. Dr. Holger Lerche is Clinical Director and Head of the Department of Neurology and Epileptology at the Hertie Institute of Clinical Brain Research at the University of Tübingen, Germany. After graduating from the Medical School at Ludwig-Maximilians University in Munich, he undertook research in neurophysiology, and residencies in neurology, psychiatry and epileptology at institutions in Germany. He was a consultant neurologist and Head of Epileptology in the Department of Neurology at the University of Ulm from 2001 to 2009, being a Heisenberg fellow of the DFG from 2003 to 2008 during which he also undertook research fellowships in London, UK, and Melbourne, Australia, before taking up his current position in Tubingen. His main research interest is to unravel the genetics and pathophysiology of inherited epilepsies and related paroxysmal disorders using a combination of genetic and neurophysiological tools. He is also interested in molecular ion channel function, their specific roles in the brain and their pharmacology. More recently, he started projects also in harmacogenetics of the epilepsies.
Holger Lerche is a former president of the German chapter of the ILAE, he was a board member of the Genetics Commission of the ILAE from 2006 to 2009 and a board member fo the ILAE Task Force for Translational Research, and has served of the Editorial Board of Epilepsia (2003-2006)
Dr. Gabriele Lignani
Dr. Gabriele Lignani received his BSc in Medical Biotechnology from the University of Milan, followed by an MSc in the same subject from the University of Genoa. In 2012 he obtained his PhD in Experimental Neuroscience from the University of Genoa, before taking up a research associate position at the Italian Institute of Technology under Prof. Fabio Benfenati. In 2014 he joined the Department of Clinical and Experimental Epilepsy at the UCL Institute of Neurology, working jointly under Dr. Stephanie Schorge and Prof. Dimitri Kullmann. Gabriele was recently awarded a Marie Skłodowska-Curie Individual Fellowship to study novel gene editing techniques for epilepsy gene therapy.
UCL Institute of Neurology - Synaptopathies
Organiser of UCL: Synaptopathies Symposium
The Synaptopathies initiative is funded by a Strategic Award from the Wellcome Trust to a team of researchers at the UCL Institute of Neurology and King’s College London, led by Professor Dimitri M Kullmann. The grant was awarded in 2014 with a start date in April 2015.
This proposal brings together complementary expertise in (i) clinical genetics and deep phenotyping of people affected by epilepsy, migraine and paroxysmal movement disorders, (ii) biophysics of presynaptic vesicle trafficking and exocytosis, (iii) the interaction of postsynaptic receptors, ion channels and perisynaptic neurotransmitter transporters, and (iv) vertebrate, invertebrate and human-derived cellular models of synaptic disorders.