Reference : UMR5070-AMAGIR-001
Nombre de Postes : 1
Workplace : TOULOUSE
Date of publication : Friday, January 20, 2023
Scientific Responsible name : Amandine GIROUSSE
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 March 2023
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
A three-year PhD contract (ANR project) is open for motivated and talented candidates (M/F) interested in adipose tissue stromal cells (ASCs) biology and muscle regeneration for a project to be performed jointly at the "Centre de Recherche en Géroscience et Réjuvénation" (Restore) and the "Institut des Maladies Métaboliques et Cardiovasculaires" (I2MC) in Toulouse, France.
This project will be carried out in the team 1 STROMAGICS led by Dr Coralie Sengenès within the RESTORE Institute UMR5070, (https://restore-lab.fr/recherche/stromagics/) and supervised by Dr Amandine GIROUSSE and Dr Coralie Sengenès.
The project focuses on the regeneration of skeletal muscles. Degenerative muscle conditions are most often characterised by ectopic fat deposition, in the form of true adipocytes between the muscle fibres, which is largely associated with the loss of mechanical and metabolic functions of skeletal muscle. However, completely unexpectedly, a transient accumulation of ectopic adipocytes is also described in healthy skeletal muscle during the regenerative process after injury, the origin and functional role of which has never been documented but which suggests a beneficial role.
We have recently demonstrated that subcutaneous adipose tissue is capable of releasing adipocyte precursors, called adipose stem/stromal cells (ASCs), which infiltrate the muscle very rapidly after injury to support its regeneration (Sastourné-Arrey et al. Nat.Comm 2023. https://doi.org/10.1038/s41467-022-35524-7).
In this project we want to demonstrate that ASCs infiltrated into the injured muscle can participate in the transient deposition of intramuscular adipocytes post injury and have a positive impact on the regeneration process. We have 4 major objectives:
i) to characterize the formation of post-injury ASC-derived adipocytes, which will provide clues to their function and highlight intervention windows for subsequent functional approaches
ii) to study the phenotype of ASC-derived adipocytes as well as their lipid signature as we believe that these metabolites may influence the regeneration process
iii) to study the influence of ASC-derived adipocytes on muscle stem cell function in vitro
iv) to observe the consequences of intramuscular adipocyte depletion during regeneration in different animal models.
This project offers the first opportunity to reconsider intramuscular adipocytes as crucial partners for muscle regeneration.
The successful candidate will
- participate in the design of the project
- use and develop methodologies
- conduct experiments
- analyze, synthesize and communicate data
- participate in the writing of research papers
The candidate will use a wide range of approaches in cell biology (cytometry, cell sorting, cell culture...), molecular biology and biochemistry (RTqPCR, lipid extraction...) on original mouse models. The PhD student will also benefit from the team's recognised expertise in advanced imaging technologies (two-photon confocal microscopy, second and third harmonic, light sheet, macroSPIM) with privileged access to these instruments. The PhD student will have access to Genotoul's platforms which have state-of-the-art equipment such as MALDI mass spectrometry imaging which will be initiated in this project. Finally, the candidate will also use techniques to measure the functional activity of muscle in mice.
The RESTORE Institute is a transdisciplinary fundamental research centre, based in Toulouse on the site of the Langlade Oncopole, which conducts original research dedicated to a global exploration of the origin of age-related physiological alterations in order to propose innovative applications in the field of geoscience and rejuvenation. A joint CNRS-EFS-INSERM unit, Restore has been home since 2021, in a new building, to a hundred or so scientists grouped into 4 autonomous teams articulated around a Centre of Expertise and Technological Resources (CERT) conducting highly collaborative and multidisciplinary research that combines experimental, theoretical and clinical approaches.
The "Stromagics" host team, led by Coralie Sengenès, comprises 15 people and focuses on repair and regeneration via the circulation of mesenchymal stromal cells (MSCs) between tissues. The scientific objectives of Stromagics are i) to identify the molecular and cellular characteristics of mobilizable adipose tissue MSCs (ASCs) and the mechanisms regulating this original dynamic and ii) to characterize this dynamic in the context of aging.
The project will also be carried out in collaboration with the Institute of Metabolic and Cardiovascular Diseases (I2MC), based at the Rangueil Hospital, which is a research centre dedicated to the study of the pathophysiology of metabolic (Obesity, Diabetes, Dyslipidemia, Hepatic Steatosis...), cardiovascular and renal diseases, bringing together 280 scientists organised into 11 teams. Our collaborator is part of the MetaDiab team (Physiopathology of Metabolic Disorders and Diabetes) aiming to elucidate the molecular mechanisms underlying insulin resistance, metabolic dysfunctions and lipid droplets in skeletal muscle and adipose tissue.
The two research sites are linked by the Téléo cable car.
Constraints and risks
- work in an animal house on mouse models in accordance with the animal protection rules laid down by law.
- hours to be adapted according to the progress of the project and the experiments in progress.
- work in staggered hours.
Candidates (M/F) must be highly motivated, hold a Master 2 or equivalent and have a strong background in animal physiology and cell biology. Training in both disciplines would be ideal. Experience in handling mouse models is essential (handling, injections, dissection). The candidate must be rigorous, have excellent organisational and teamwork skills, and be able to speak and write in English (French is not required).
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