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Funded PhD project

Biomarkers for the diagnosis of pancreatic cancer

Published on 8 March 2023
Project summary
Pancreas is an amphicrine gland with and endocrine function that regulates the glycaemia while the exocrine function allow the secretion of digestive juices to participate to the digestion. These two functions are performed by different cells: the islet of Langerhans for the endocrine function and epithelial cells for the exocrine function. Both functions can be deregulated, leading to dramatic diseases, diabetes mellitus and pancreatic cancer. Pancreatic cancer is one of the most deadly cancers of the world, being the 4th largest cause of death by cancer in Europe with only 4.6 months after diagnosis median survival in Europe. Interestingly, epidemiological studies show that diabetes is a risk factor in pancreatic cancer development but the molecular mechanisms involved are still unknown.
The main goal of this project is to build a new physiological model of pancreas diseases including diabetes mellitus and pancreatic cancer. We are developing an amphicrine pancreas-on-chip using 3D cultures of Langerhans islets embedded in a commercial hydrogel or in patient decellularized extracellular matrix in a microfluidic device, that also contain a channel filled by epithelial pancreatic cells (untransformed or derived from patient biopsies). This device can then be perfused and studied for extended time.
The aim is now to improve the device and to study the neoplastic transformation of exocrine epithelial cells in the diabetic context, in order to identify new very early biomarkers of pancreatic carcinogenesis that could be uses in diagnostic. In particular, we will analyze the secretome, in search of circulating biomarkers, but also use transcriptomics, genomics and phenotypic analysis, to identify other types of possible biomarkers. The candidate will benefit from an outstanding scientific environment with close collaborations with the digestive oncologists from the CHU Grenoble Alpes and with the technologists of the CEA-LETI, that can eventually make a difference for the benefit of patient.
As a PhD student in our team, the candidate will have the opportunity to receive specific training in methodological approaches and cutting-edge methods, both related to the specific project and beyond. The candidate will also be encouraged to present research results at national and international conferences, providing him/her with valuable opportunities to share the work and engage with other leading scholars in the field.

Techniques to acquire
Cell biology, microscopy (including 3D techniques, confocal...), molecular biology (RTqPCR, western-blot), 3D printing, microfluidics, immunostaining, ...

Environment
The Biosciences and bioengineering for health laboratory (BGE) consists of three teams labelled by the UGA, CEA and INSERM.
- The Biomics team
- The EDyP team
- The Gen&Chem team
Building on their long-standing experience and collaborative practices, these three teams conduct complementary scientific and technological work and coordinate their research to implement the overall scientific project aimed at identifying biomarkers and therapeutic targets, studying their function, using them for diagnosis and developing new therapeutic solutions in the form of drug candidates or biotherapies derived from cell and tissue engineering, as well as tools for bioinformatics analysis of experimental data, mainly in metabolic diseases and cancer. This PhD will be performed in the Biomics team, leaded by Xavier Gidrol.

Candidate profile
Master in Biology / Cell Biology / Bioengineering / Biotechnology / Molecular Biology highly motivated
Ability to work independently and collaboratively as a member of a team.
Scientifically rigorous.
Open-minded and motivated personality.
Fluent in scientific English.
Candidates with experience in cell culture are encouraged to apply. Experience with imaging, molecular biology, and microfluidics are highly desirable. Experience in statistics is also desirable.

How to apply
Please provide a cover letter (1 page) with a CV (2 page maximum), and at least one referee who can be directly contacted, in a single (!) PDF file) until 15.04.2023. Oral discussion in April, and final decision before May, 15th. Your supporting statement should outline your academic interests, prior research experience and reasons for wishing to undertake this project.

Contract
3 years CEA grant funding, starting from Oct 2023.

Supervisors
Flora Clément and Maxim Balakirev.

Keywords
Pancreatic cancer, organ-on-chip, diabetes, microfluidics, biomarkers.

Contact
Flora Clément