Welcome to the Synaptopathies website

The Synaptopathies (SYNaPS) study group is an initiative, funded by the Wellcome Trust, awarded to a team of researchers at the UCL Institute of Neurology.

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.

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.

Please see also the SYNAPS Study Group website.

Miss Stephanie Efthymiou
s.efthymiou@ucl.ac.uk
Tel: 02034484069

Aims

Our goal is to understand the mechanisms of neurological diseases characterised by genetic disorders of synaptic function, and apply this to identify therapeutic targets.

We address the following questions:

  • How do combinations of inherited variants in synaptic genes interact to affect synaptic function?
  • Can inherited disorders of multiple synaptic genes be recreated in invertebrate models and in neurons derived from patients?
  • How does synaptic homeostasis interact with inherited genetic variability in synaptic proteins?
  • How do alterations in synaptic function affect the operation of small circuits?
  • How can an improved understanding of genetic synaptopathies be harnessed to treat paroxysmal neurological disorders?

Collaborators

  • Matthew W Walker (UCL)
  • John Hardy (UCL)
  • Dennis Kaetzel (UCL)
  • Ivan Pavlov (UCL)
  • Dmitri Rusakov (UCL)
  • Yuri Korchev (Imperial College)
  • Kailash Bhatia (UCL)
  • Nicholas W Wood (UCL)
  • Sameer Zuberi (Glasgow)
  • David Beeson (Oxford)
  • Manju Kurian (UCL)
  • Lydia Teboul (Harwell)
  • Prab Prabhakar (Great Ormond Street Hospital)
  • Giampietro Schiavo (UCL)
  • Alan Pittman (UCL)
  • Vincent Plagnol (UCL)
  • Roope Mannikko (UCL)
  • Mark I Rees (Swansea)
  • Patrick Nolan (MRC Harwell)
  • Yulia Timofeeva (Warwick)
  • Patrick Chinnery (Cambridge)

PIs

  • Dimitri M Kullmann (lead principal investigator)
  • Henry Houlden (deputy lead PI)
  • Michael G Hanna (co-PI)
  • James Jepson (co-PI)
  • James E Rothman (co-PI)
  • Stephanie Schorge (co-PI)
  • Kirill Volynski (co-PI)

Please see also Meet the team on the SYNAPS Study group website