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Reference : UMR7288-CHRESS-003
Workplace : MARSEILLE,MARSEILLE 09
Date of publication : Friday, October 09, 2020
Scientific Responsible name : Aziz MOQRICH
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 January 2021
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
In recent years, we have discovered that the neuropeptide TAFA4, specifically expressed in a subpopulation of low threshold mechanoreceptors type C (LTMR-C), is capable of reversing mechanical hypersensitivity induced by lesional pain. We have also shown that mice with the TAFA4 gene (TAFA4-KO) inactivated show prolonged mechanical hypersensitivity following inflammatory or neuropathic pain. In addition, TAFA4 increases the frequency of spontaneous inhibitory post-synaptic currents in the inner layer II of my spinal cord (L-IIi-SC).
All these data led us to propose a model in which TAFA4 is constitutively released by L-IIi-SC. Under normal conditions, TAFA4 binds to its LRP1 receptor and activates a signaling pathway that negatively modulates L-IIi-SC inhibitory interneurons. This negative modulation is suppressed after peripheral injury, leading to so-called mechanical allodynia.
The proposed project aims to test this hypothesis using state-of-the-art methodologies such as behavioral pharmacology, high-throughput RNA sequencing, proteomics and phosphoproteomics, in order to meet 2 objectives :
- What are the cell types of L-IIi-SC on which TAFA4 acts to exert its pain-relieving effect?
- What are the signalling pathways downstream of the TAFA4/LRP1 interaction?
Candidates should have a strong motivation for basic research and a good knowledge of molecular and cellular neurobiology. A first experience in the field of pain would be highly appreciated.
The IBDM, located on the Luminy Campus, includes about 240 permanent staff members (Researchers, Lecturers, Researchers, Engineers and Technicians) and non-permanent staff members (CDD, Post doc, PhD students, trainees) spread over 21 research teams and 11 technical and service platforms. The IBDM is a joint research unit under the supervision of the CNRS and the AMU, which explores the field of Developmental Biology, Neurosciences and associated pathologies.
The activity will be carried out within the "Chronic Pain: Molecular and Cellular Mechanisms" team led by Aziz Moqrich.
As the team is composed of several nationalities, English language skills are essential.
Constraints and risks
Please send a CV, a cover letter and ideally a letter of recommendation.
Any application with a higher level of education will not be accepted.
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