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PhD (M/F) Labd on chip for the separation of circulating adipocyte stem cells

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Français - Anglais

Date Limite Candidature : jeudi 13 mai 2021

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General information

Reference : UPR8001-ANNGUE-002
Workplace : TOULOUSE
Date of publication : Thursday, April 22, 2021
Scientific Responsible name : Anne-Marie Gué
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 September 2021
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly

Description of the thesis topic

Type 2 diabetes (T2D) currently affects more than 382 million people worldwide. Numerous side-effects are associated with T2DM, including an increased risk of cardiovascular disease, kidney failure, lower limb amputation and retinopathy. Currently, early detection of T2DM is hampered by the lack of a predictive biomarker. However, at the time of diagnosis, a large number of new diabetics already have side effects. It is therefore clear that the identification of predictive biomarkers for T2DM is a major public health issue.
We have shown for the first time that a high-fat diet triggers the release of adipose stem cells (ASCs) from the subcutaneous adipose tissue resulting in the formation of ectopic adipocytes leading to the development of T2DM. These results show that the level of circulating ASCs reflects the ectopic fat content, which is known to be a major contributor to the development of T2DM. Our work therefore suggests that the level of circulating ASCs can be considered as a predictive biomarker for T2DM.
In this context, the objective of this project is to develop a new method for the early diagnosis of T2DM based on the separation and detection of circulating ASCs in blood using an original microfluidic approach allowing the direct isolation of ASCs from whole blood.
The objective of the thesis is, in this context, to develop a immunological exclusion method based on "cell rolling". The latter uses the mechanisms of transient adhesion of hematopoietic cells on surfaces functionalized by antibodies of interest and is inspired by physiological mechanisms occurring in blood vessels.
The work will require the development and implementation of biofunctionalization and microfabrication technologies of microfluidic chips and the validation of their functionality from synthetic samples to murine blood samples.

Work Context

The LAAS-CNRS is a CNRS unit located in Toulouse. It has a clean room of 1500m2, allowing the realization of microfluidic devices as well as a biology and microfluidics experimentation room of 400m2. The PhD student will be hosted in the Micro and Nanofluidics for Life Sciences and Environment Team (MILE)
The project is based on a close collaboration between 3 laboratories in Toulouse, the LAAS, the TBI and the RESTORE laboratory, which have already been working together for 3 years. The technological developments will be carried out at LAAS, the first levels of characterization at LAAS and TBI, on the basis of samples provided by the RESTORE laboratory. The cohorts of diabetic mice, their validation, the preparation of the murine samples and the biological validations will be carried out in the RESTORE laboratory.

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