Ictogenicity of focal cortical dysplasia at single-cell and network level and possible therapeutic interventions
PhD project: Ictogenicity of focal cortical dysplasia at single-cell and network level and possible therapeutic interventions
Focal cortical dysplasia (FCD) is a local malformation of the cerebral cortex that is highly ictogenic and often causes catastrophic drug-refractory epilepsy that appears in early childhood. The way how different neurons within FCD produce seizures and how the seizures spread behind the FCD borders remains elusive. We have recently adopted a plausible model introducing real FCD-associated human mutation in mice and rats. The PhD project aims to characterize the role of specific cell types in the altered FCD cytoarchitecture, the projections that enable seizure spreading and testing interventions that could interrupt specific steps of seizure generating process. To achieve these goals, FCD models will be prepared using in utero electroporation in several mouse strains with identified specific inhibitory interneurons and principal cells. State-of-the-art In vitro and in vivo electrophysiological methods will be combined with the latest and sophisticated in vivo techniques of optical imaging, optogenetics and chemogenetics.
Candidate’s profile (requirements):
We are seeking outstanding candidates that are eager to play a significant role in a real bench-to-bedside translational research and become a member of an agile multidisciplinary team composed of neuroscientists, physicists, neurologists etc. Candidate must have, or be finishing a master's degree or equivalent in molecular biology, biochemistry, physiology, medicine or related fields. Fluent English. Earlier experience with surgical, electrophysiological and microscopy techniques is beneficial, but not a requirement. Candidate should be familiar with working with literature.
Lim JS, Kim WI, Kang HC, Kim SH, Park AH, Park EK, Cho YW, Kim S, Kim HM, Kim JA, Kim J, Rhee H, Kang SG, Kim HD, Kim D, Kim DS, Lee JH. Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy. Nature Medicine 2015 Apr;21(4):395-400.
Rossi LF, Kullmann DM, Wykes RC. The Enlightened Brain: Novel Imaging Methods Focus on Epileptic Networks at Multiple Scales. Frontiers in Cellular Neuroscience. 2018 Mar 26;12:82.
Chang WC, Kudláček J, Hlinka J, Chvojka J, Hadrava M, Kumpošt V, Powell AD, Janča R, Maturana MI, Karoly PJ, Freestone DR, Cook MJ, Paluš M, Otáhal J, Jefferys JGR, Jiruška P. Loss of neuronal network resilience precedes seizures and determines the ictogenic nature of interictal synaptic perturbations. Nature Neuroscience 2018, 21(12), 1742-1752 .
Supervisor: Prof. Premysl Jiruska, M.D., Ph.D.