The NeurIT team is recruiting its next PhD student
Project description
Peripheral neuropathies (PN) are a major public health issue, with an estimated prevalence of 700,000 people in France, and are at the heart of the research work of our laboratory, UR20218 NeurIT, directed by Prof. F. Sturtz, associated with the Biochemistry and Molecular Biology Department (labelled LBMR in 2021) and the National Reference Centre for Peripheral Neuropathies (PN) at Limoges University Hospital, directed by Prof. L. Magy (co-director of NeurIT). Among these, Charcot-Marie-Tooth disease (CMT) is the most common hereditary NP. More than 100 genes may be involved in this disease, which has no effective treatment. The study of this disease remains tricky due to the impossibility of gaining direct access to patients’ nerve cells and the limitations of animal models, with problems of species transferability, ethical constraints and high costs. To address these issues, our research unit uses human induced pluripotent stem cells (hiPSC), derived from skin cells of patients with CMT, which can be differentiated into motor neurons, Schwann cells or muscle cells, the cells that make up the neuromuscular junction.
The main objective of our project is to develop an original 3D in-vitro neuromuscular junction model combining the three cell types. This will enable us to answer fundamental questions about the pathophysiological mechanisms involved in CMT, but also in the longer term to identify therapeutic molecules using a model that closely resembles the physiology of the individual affected.
This project is based on pooling the specific expertise of three laboratories in the Nouvelle Aquitaine region: the XLIM-UMR-CNRS7252 laboratory (Univ Limoges), which is developing, among other things, microchips using 3D printing that will enable the assembly of these cell types; the PRéTI-UR24184-UFR SFA laboratory (Univ Poitiers), which has expertise in the 2D and 3D development of in-vitro muscle cells, including cells derived from hiPSCs, as well as methods enabling functional studies of these models (calcium imaging), and using original approaches (optogenetics); the UR20218 NeurIT laboratory (Univ Limoges), which has set up the hiPSC technology and their differentiation in Limoges. Preliminary results obtained in the laboratory on healthy cells show that motor neuron/Schwann cell co-culture promotes the extension of neuronal extensions. In parallel with these experiments, a collaboration with the Mitolab UMR Inserm U1083 – CNRS 6015 team in Angers will enable us to carry out oxygraphy, metabolomics and lipidomics experiments to clarify the role of GDAP1 in this pathology.
Once this model has been characterised on healthy cells, this complex culture with the three cell types will be applied to cells from patients in order to understand the physiopathological mechanisms involved in CMT at the neuromuscular junction, and may make it possible to identify pharmacological alternatives in the longer term, in conjunction with the local start-up CURLIM.
Once this model has been characterised on healthy cells, this complex culture with the three cell types will be applied to cells from patients in order to understand the physiopathological mechanisms involved in CMT at the neuromuscular junction, and may make it possible to identify pharmacological alternatives in the longer term, in conjunction with the local start-up CURLIM.
Profile and skills required
We are looking for a student who is highly motivated by medical research and cell biology, in particular the study and use of stem cells. We give preference to students with previous experience in cell culture, without this being a limiting factor for recruitment. A 2 to 3-month training course on iPSc culture will be given at the University of Limoges laboratory (NeurIT). Solid knowledge of genetics, molecular biology, biochemistry and neurology is required, as well as a good command of English.
During the thesis, the PhD candidate will be required to travel to Poitiers and Angers. The candidate must be able to integrate and collaborate easily with other teams.
The PhD student will take part in working groups with socio-economic players in the region, such as InvivoLim, which will enable him/her to benefit from meetings with researchers from the University of Limoges and companies in the Nouvelle-Aquitaine region.
The doctoral student will also have the opportunity to present his or her work to the general public at meetings with socio-economic players on the outskirts of Limoges (Saint-Yrieix town hall, Rotary, Club 41, Lions Club), as well as through interviews with local radio stations and the press, and presentations in schools, as has already been planned for former doctoral students in our research team. It is important to note that the doctoral student will be actively solicited to apply for future EPST (Établissements publics à caractère scientifique et technologique) jobs. In the longer term, he/she may also apply for a teaching position at the University of Limoges. Finally, if he/she so wishes, he/she can teach (TD, ED, etc.) at the Faculties of Medicine and Pharmacy in Limoges.Niveau de français requis: Compétent/Courant: Vous pouvez utiliser la langue avec aisance et facilité en argumentant sur des sujets complexes.
During the thesis, the PhD candidate will be required to travel to Poitiers and Angers. The candidate must be able to integrate and collaborate easily with other teams.
The PhD student will take part in working groups with socio-economic players in the region, such as InvivoLim, which will enable him/her to benefit from meetings with researchers from the University of Limoges and companies in the Nouvelle-Aquitaine region.
The doctoral student will also have the opportunity to present his or her work to the general public at meetings with socio-economic players on the outskirts of Limoges (Saint-Yrieix town hall, Rotary, Club 41, Lions Club), as well as through interviews with local radio stations and the press, and presentations in schools, as has already been planned for former doctoral students in our research team. It is important to note that the doctoral student will be actively solicited to apply for future EPST (Établissements publics à caractère scientifique et technologique) jobs. In the longer term, he/she may also apply for a teaching position at the University of Limoges. Finally, if he/she so wishes, he/she can teach (TD, ED, etc.) at the Faculties of Medicine and Pharmacy in Limoges.Niveau de français requis: Compétent/Courant: Vous pouvez utiliser la langue avec aisance et facilité en argumentant sur des sujets complexes.
Niveau d’anglais requis: Intermédiaire supérieur: Vous pouvez utiliser la langue de manière efficace et vous exprimer précisément.
Further information
All information here : https://adum.fr/as/ed/voirproposition.pl?langue=&site=unilimBCS&matricule_prop=63898#version