PhD position (M/F) in Biology: “Analysis of dynamic interactions between adipose tissue and pancreatic islets using a multi-organ-on-a-chip microfluidic approach” (36 months, Bordeaux)

Job Description

Thesis Subject

Thesis title: Analysis of dynamic interactions between adipose tissue and pancreatic islets using a microfluidic multiorgan-on-chip

1) Funding:
The PhD project is funded by the ANR PRC ISADIPO (ANR-25-CE14-7667), coordinated by M. Raoux, group leader at the CBMN laboratory (UMR 5248, CNRS, University of Bordeaux), who will also serve as the PhD supervisor. The project will be carried out in collaboration with P.-D. Denechaud (I2MC Inserm U1297, Toulouse), partner of the ANR ISADIPO project.
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2) Background:
Dysregulation of glucose and lipid metabolism is associated with pancreatic islet dysfunction and is a major hallmark of type 2 diabetes (T2D). Therapies that preserve pancreatic beta-cell function improve T2D progression. Glucose-lipid homeostasis involves inter-organ communication between adipose tissue and pancreatic islets, which remains poorly understood, particularly regarding the influence of adipocyte lipolysis on islet hormone secretion under physiological and pathological conditions. This limitation is due to the lack of: (1) validated genetic tools to abolish fatty acid production from adipose tissue, and (2) relevant ex vivo multi-organ models capable of measuring, in real time, the influence of adipocytes on islet function.
Our preliminary data, our expertise in pancreatic islets and organ-on-chip technologies, and access to an inducible triple-transgenic mouse model enabling adipocyte lipolysis inactivation (through collaboration with I2MC, Toulouse) now make it possible to address this critical question regarding the influence of adipose tissue on pancreatic islets under both physiological and pathological conditions.
The project will consist of developing a 2-organ-on-chip (2-OOC) adipocyte–islet microfluidic platform to determine the influence of adipocyte lipolysis on islet electrical activity, intercellular coupling, and hormone secretion during protocols mimicking fasting and feeding periods, with and without lipolysis, under physiological and pathological conditions. The 2-OOC system will then be adapted into a human 2-OOC platform to validate key aspects of our hypotheses in humans.
Understanding these inter-organ communications will accelerate the identification of therapeutic targets aimed at improving the (mal)adaptive function of pancreatic islets in T2D.
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3) Research Activities
Theme:
Study of nutritional homeostasis and its pathological dysregulation using multi-organ-on-chip systems.
Field:
This project lies at the intersection of physiology (nutritional regulation), pathophysiology (diabetes, obesity), and biotechnology (organ-on-chip technologies).
Objectives:
Develop a 2-organ-on-chip (2-OOC) adipocyte–islet microfluidic platform to determine the influence of adipocyte lipolysis on islet electrical and secretory activity during protocols mimicking fasting and feeding periods under both physiological and pathological conditions.
Importance of the topic:
Obesity-associated diabetes is increasing dramatically worldwide and represents a major global health concern. These are multi-organ diseases that can be better understood through multi-organ-on-chip approaches. Such approaches make it possible to characterize functional interactions between organs and monitor them in real time, thereby improving our understanding and facilitating the identification of new therapeutic targets.
Methods:
The PhD candidate will use our microfluidic multiorgan-on-chip systems based on microelectrode arrays. Adipocytes will be obtained from inducible tissue-specific triple-transgenic mice, while pancreatic islets will be isolated from wild-type mice. A humanized multiorgan-on-chip platform containing human pancreatic islets and lipolysis-deficient human adipocytes will be used to confirm the main findings in humans.
Expected results:
• An innovative multi-organ-on-chip system enabling investigation of dynamic interactions between adipose tissue and pancreatic islets;
• Improved understanding of these inter-organ communications under physiological conditions (nutritional homeostasis) and pathological conditions (high-fat diet, glucotoxicity/lipotoxicity, etc.), leading to the identification of novel therapeutic targets.
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4) Required Skills
The candidate should hold a Research Master's degree (Master 2) or equivalent qualification in biology (Cell Biology, Physiology/Pathophysiology, Biotechnology, Neuroscience, Nutrition, Biochemistry, etc.). The candidate should have demonstrated scientific rigor, organizational skills, scientific curiosity, the ability to work independently, and strong motivation to pursue a PhD.
Knowledge of pancreatic islet biology and/or adipose tissue biology and/or organ- and organoid-on-chip technologies, as well as practical skills in electrophysiology or microfluidics, would be advantageous but are not mandatory, as the laboratory has extensive experience in effectively training new members (within approximately 2 months).
Most importantly, the candidate should be interested in collaborative research projects and mutual scientific enrichment.

Your Work Environment

Thesis location:
The PhD candidate will work within the Cellular Biology & Biosensors group, a dynamic research team within the interdisciplinary CBMN laboratory (Institute of Chemistry & Biology of Membranes & Nano-objects, UMR 5248, CNRS, University of Bordeaux). The group is led by M. Raoux and currently includes 2 Professors, 2 Associate Professors, 2 permanent research engineers, 1 fixed-term research engineer, 1 postdoctoral researcher, and 3 PhD students.

Supervision, training, and research monitoring:
Training in laboratory techniques and analytical methods will be provided both within the host laboratory and partner laboratories. The candidate will enroll in theoretical and practical training courses relevant to the scientific and professional project.
Detailed meetings with the supervisor will take place every two weeks, alongside weekly group meetings. A biweekly Journal Club brings together Master's students, PhD candidates, postdoctoral researchers, contract engineers, and researchers.
A thesis committee involving the mentor and external experts is organized annually.
The supervisor places strong emphasis on communication with and among PhD students, as well as on their professional development.

Scientific, material, safety, and financial conditions:
The PhD candidate will receive training in health and safety regulations immediately upon joining the laboratory. Human cells received are certified pathogen-free. No particularly hazardous chemical manipulations are planned.
The team currently benefits from several funded projects (including four ANR grants), ensuring full support for experimental work.

International collaborations:
• Belgium: M. Cnop; J.-C. Jonas
• Switzerland: P. Herrera
• Netherlands: A. Zaldumbide
• Portugal: Q. Zhang
• UK: B. Hastoy
Collaborations in France:
• P.-D. Denechaud (Toulouse) – adipose tissue and transgenic models
• S. Renaud, J. Cieslak, M. Abbas(Bordeaux) – bioelectronics, signal processing, modeling
• A. Kuhn (Bordeaux)– electrochemistry, biosensing
• E. Cloutet (Bordeaux) – organic chemistry, biosensing
Research valorization:
Participation in national and international conferences (SFD, EASD, EUROOCS, EISG). Publications in high-impact journals and possible patent applications.

Constraints and risks

Occasional travel to Toulouse may be required (approximately 2 hours by train or car), covered by the laboratory.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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