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Progressive Myoclonus Epilepsy: GOSR2 mediated mechanisms

Project details

Roman Praschberger
UCL Queen Square Institute of Neurology
Research area
Funding type
PhD studentship
Awarded in
January 2013
January 2018

Roman Praschberger joined the PhD programme in Clinical Neurosciences at UCL Institute of Neurology in 2013, funded by a Brain Research UK studentship.

Following completion of his medical degree in 2012, Roman wanted to acquire a solid understanding of basic neuroscience research and follow his deep interest in molecular and cellular disease mechanisms, in order to pursue a career as a clinician-scientist in neurology.

He was awarded his PhD in 2018 and has now taken up a neurology training post at the University Hospital of Tübingen in Germany.  

Understanding the mechanisms of GOSR2-mediated progressive myoclonus epilepsy

GOSR2-mediated progressive myoclonus epilepsy is a severe epilepsy syndrome caused by a mutation in the GOSR2 gene. It is characterised by an early disease onset, at around three years of age, and core neurological symptoms including lack of motor co-ordination, muscle jerks, and generalised epilepsy.

In order to study the genetics of this disorder, Roman assembled a set of DNA samples from patients suffering from progressive myoclonus epilepsy (PME) and screened these to look for mutations in certain genes including the GOSR2 gene. This led to the discovery of a second, previously unknown, mutation in GOSR2.

He then went on to study the mechanisms by which the genetic mutations lead to the cellular abnormalities that cause abnormal brain function. To do this, he developed a simple but genetically very powerful model using the fruit fly Drosophila.

The relationship between Drosophila and human genes is so close that often the sequences of newly discovered human genes, including GOSR2, can be matched with equivalent genes in the fly. It is relatively straightforward to mutate Drosophila genes and study the consequences. It is also very efficient as the flies have a short generation time and are inexpensive to maintain.

Mutations in the Drosophila GOSR2 gene cause severe neuronal defects and Roman’s work has revealed for the first time the neuronal abnormalities that underlie this disorder and ultimately give rise to the lack of coordination and epilepsy in human patients.

His research has provided a comprehensive understanding of this devastating form of epilepsy and the process by which the genetic mutations cause neuronal damage, which in turn gives rise to its symptoms. His discovery of a novel mutation in GOSR2 has implications for the diagnosis of PME patients, as it suggests that this region of the gene should also be included when potential disease-causing defects in GOSR2 are investigated.

As well as being relevant to GOSR2-PME, Roman’s work has also yielded novel insights into the cell biology of neurons, which might also be relevant for other neurological diseases.

What next for Roman?

Through our PhD studentships, we aim to nurture the development of promising researchers who we hope will go on to develop long and illustrious careers in brain research. In this way we are investing in the future of brain research, and the next generation of research leaders.

Not only did our funding support the important research that Roman undertook during his PhD, which led to the publication of two first-author papers, but it has helped him along the path towards a career as an independent researcher.

In pursuit of his intended career as an academic neurologist, Roman has now taken up a neurology training post at the University Hospital of Tübingen in Germany, where he has 50 per cent of his time set aside for research.

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