Job ID: 113508

Identification of biomarkers of sudden unexplained death in epilepsy (SUDEP) in mouse models, use in prediction and prevention.

Position: Ph.D. Student

Deadline: 15 July 2023

Employment Start Date: 1 September 2023

Contract Length: 3 Years

City: Valbonne

Country: France

Institution: CNRS and University Cote d'Azur

Department: Institute of Molecular and Cellular Pharmacology

Description:

PhD thesis funded by the European Innovation Council (EIC) Pathfinder Neurosense project: the overall aim is to develop prototypes of artificial intelligence-assisted medical devices to predict epileptic seizures that can cause mortality and trigger automatic administration of emergency drugs to prevent SUDEP, i.e. the sudden death of an epileptic person in the absence of other abnormal conditions. It is assumed that SUDEP may be caused by brain stem dysfunctions, but it is currently impossible to predict or prevent. The rate of SUDEP is particularly high in Dravet syndrome (DS), a severe, drug-resistant developmental and epileptic encephalopathy caused by mutations in the Nav1.1/SCN1A sodium channel.

The PhD student will use transgenic mouse models of DS and other epileptic mouse models, microdialysis experiments and in vivo electrophysiology to validate the hypothesis that the neuromodulator of interest is involved in the pathological mechanism of SUDEP and can be used as a biomarker to predict and prevent it.

Activities

– Stereotactic surgery for implantation of electrodes, microdialysis probes and optogenetic fibers. –Chronic electrophysiological recordings (ECoG, LFP) in mice and signal analysis. – In vivo optogenetics in mice. – Induction of epileptic seizures (hyperthermia and fluorethyl). – Pharmacological treatments. –  Statistical analysis. – Literature search and improvement/adaptation of techniques and analyses according to research projects. – Writing of scientific papers.

Qualifications

– Master degree in neurobiology, neuroscience, biophysics, physiology or related disciplines. – Interest in performing animal experiments such as microdialysis techniques, intracerebral electrophysiological recordings (ECoG, LFP), in vivo optogenetics, which will be supervisedby team members. Willingness to design, plan and execute complex experiments, with some autonomy in experiment management. – Ability to work as part of a team. – Good level of oral and written English.

Work context

The Institute of Molecular and Cellular Pharmacology (IPMC) is a joint research unit (UMR 7275) of the CNRS and the Université Côte d’Azur (220 people, 8000 m2 of buildings). Its 20 world-class research teams benefit from a high-level technological environment in mouse phenotyping, electrophysiology, molecular and cellular biology, imaging, cytometry, biomolecule analysis, functional genomics and integrative biology. Massimo Mantegazza’s team has recognized expertise in the development and study of in vivo, ex vivo and in vitro genetic models of epilepsy:

Guerrini R., Conti V., Mantegazza M et al. (2023) Physiological Reviews https://doi.org/10.1152/physrev.00063.2021

Mantegazza M., Cestèle S and Catterall W.A. (2021) Physiological Reviews 101(4):1633-1689. https://doi.org/10.1152/physrev.00025.2020

Mantegazza M. and Broccoli V. (2019) Epilepsia 60(S3):S25-S38. https://doi.org/10.1111/epi.14700

Application procedure:

– Cover letter (max 2 pages) addressing the essential criteria listed above and indicating the email address of 2 references. – Detailed CV (no space restriction) with transcript of Master’s grades.

IMPORTANT: You must use the following link to apply:

https://emploi.cnrs.fr//Offres/Doctorant/UMR7275-MASMAN-012/Default.aspx

Further information:

Mantegazza’s team and IPMC:

https://www.ipmc.cnrs.fr?page=mantegazza

European Innovation Council (EIC) – Horizon Europe:

https://neurosense-project.eu/

https://www.cote-azur.cnrs.fr/fr/cnrsinfo/eic-pathfinder-open-2021-3-laureats-issus-de-laboratoires-azureens-crhea-inphyni-ipmc