Detection of Synaptic vesicle glycoprotein 2A (SV2A) as Biomarker for Epileptogenesis

Basic mentor

Jens H. Mikkelsen, Professor, Dr.med., Department of Neuroscience, UCPH.

Clinical mentor

Lars Pinborg, Assoc Professor, Dr.med., Epilepsy Clinic, Department of Clinical Medicine, UCPH.

Framework

The mentor team offers the candidate to work in two exciting environments of focusing on the same goals, namely developing novel diagnostics for patients with neurodegenerative disease (in this program we focus on epilepsy). Using different tools, the project converges in better understanding of diagnosing changes in pre-synapse biochemistry and plasticity in the human brain. The experimental team uses protein and mRNA detection methods in experimental animals and human tissues to determine the level of biomarkers (here SV2A) and correlate these changes with synapse structure and formation. The clinical team translates these results to define conditions by which determination of SV2A binding in vivo can be used as a novel diagnostic in neurology patients

Project synopsis

Several lines of evidence have demonstrated that the vesicle membrane protein, Synaptic Vesicle Glycoprotein 2A (SV2A), is involved in epilepsy. First, SV2A is the target of antiepileptic drugs, levetiracetam and brivaracetam second, SV2A levels are decreased in the hippocampus and cortex in patients with treatment resistant epilepsy.

This mentor team aims to validate and explore the potential of SV2A detection methods in cells and tissues from experimental models and humans. Experimentally, the basic neuroscience team will look at the binding (3H-UCB-J, levetiracetam and brivaracetam), mRNA expression and protein levels in tissues from animals and humans. The human material comes from neurosurgical resections, allowing to study all these variables in non-degraded tissues. We will also determine the spatial and temporal changes in SV2A in several models of epilepsy (systemic and intracerebral kainic acid, pilocarpine, electrical convulsions), and determine whether changes actually reflect synapse formations. Simultaneously, the clinical team will work on brain imaging to determine the binding and distribution of SV2A in the human brain.

Fellow candidate

  • PhD with strong interests in neuroscience
  • Education in medicine, biochemistry, cell biology, neuroscience or similar
  • Experience with animal models, protein biochemistry, neuropharmacology or similar
  • Insight in clinical neurology

Contact

Basic mentor Jens H. Mikkelsen: d239097@dadlnet.dk