PhD : Extracellular matrix from marine origin: toward a 3D cell culture model for screening of therapeutic molecules (Marcell-3D in Nantes, Pays de la Loire, FR at IFREMER - ENGLISH

Job Description

Job title : PhD : Extracellular matrix from marine origin: toward a 3D cell culture model for screening of therapeutic molecules (Marcell-3D) (H/F)

Reference: PV-2024-1467/1

Department/Office:

Duration in months :36

Start date:

Deadline for applications:15/05/2024

General areas of responsibility

EM3B laboratory (fr. Ecosystèmes Microbiens et Molécules Marines pour les Biotechnologies) efficiently contributes to the science through fundamental research on marine bacteria from particular environments (food matrices, deep-sea hydrothermal vents) and their valuable metabolites, in particular antimicrobial peptides and exopolysaccharides. This fundamental knowledge opens the way toward innovative developments already explored in food (biopreservation) and medicine (tissue engineering, cancer treatment). https://em3b.ifremer.fr/EM3B-en-bref.

Three-dimensional (3D) culture models in oncology constitute relevant tools for screening of therapeutic molecules. By reconstructing the complex tumor environment, these in vitro models increase the chances of identifying new drug candidates and thus reduce the number of preclinical animal tests. The 3D model most used in oncology is the culture of cancer cell lines into spheroids or cells from primary cultures into organoids. In order to further mimic the surrounding extracellular environment, these 3D cultures can be integrated into highly hydrated matrices, made of synthetic or natural polymers, called hydrogels. Through their biological and mechanical properties, hydrogels influence cellular processes, such as viability, migration, proliferation, differentiation and adhesion. Thus, in order to control cellular behavior, it is essential to dispose artificial extracellular matrices with established functional properties.

In this context, the objective of the thesis is to develop a standardized artificial 3D extracellular matrix with controlled physicochemical and mechanical properties to study the responses of encapsulated cancer cells to new therapeutic approaches. To determine the impact of the established matrix on the viability, morphology, proliferation, differentiation and sensitivity to drugs, cancer cells and cells of their environment (stromal cells, immune cells) formed by lung, pancreas, breast and bone cancers will be encapsulated in the hydrogels obtained. The matrix allowing the optimal and reproducible development of cellular responses will be selected for the screening of therapeutic molecules used in oncology (immunotherapy, chemotherapy).

The PhD program is organized into 2 main steps: Step (1) is dedicated to the formulation of hydrogels based on EPS from the Ifremer collection and marine collagen, and their physicochemical and mechanical characterizations. Different parameters (EPS/collagen ratio, concentrations, molecular weight) will be studied to obtain homogeneous and stable hydrogels in cell culture medium. The impact of the composition of hydrogels on their physicochemical and mechanical properties will then be determined by Atomic Force Microscopy (AFM) in a physiological environment. Step (2) is devoted to the preparation and encapsulation of cancer cells in the matrices, followed by the characterization of cellular properties in response to various treatments. Cell cultures produced in 3D will make it possible to screen different therapeutic agents alone or in combination.

Hydrogel, mechanical properties, cell activity, cancer, therapeutic molecule

Required Knowledge, skills, and characteristics

• Master 2 in physico-chemistry of polymers or biomaterials, cellular biology.
• Skills in analytical chemistry, techniques for biomaterial characterization.
• Excellent written and oral communication skills in English

Specific working conditions

• In the first year of the thesis, the PhD student will work on the development and physicochemical characterization of EPS-collagen matrices at Ifremer. The characterization of the mechanical properties by AFM will be carried out in parallel at Institut des Matériaux de Nantes Jean Rouxel (IMN) (co-director Stéphane Cuenot). The second year and the beginning of the third year of PhD devoted to the encapsulation of cancer cells in matrices, followed by the characterization of cellular properties in response to various treatments, will be carried out at UMR 6286 US2B and Institut de Cancérologie de l’Ouest in Nantes (co-supervisor Javier Munoz-Garcia).

• PhD is a real opportunity to work on Ifremer's scientific and technological priority themes. It entitles the holder to a gross monthly salary of 2300 euros for a period of 3 years, which cannot be combined with other scholarships. 

Your application file must include:

• a curriculum vitae 
• a covering letter
• a reference letter
• an academic transcript (Bachelor + Master 1 and first semester Master 2)

Your application must be compiled into 2 PDF files, up to 3 MB for each file.

The deadline for applications is May 15th, 2024. Nevertheless, we strongly urge you to let us know as soon as possible of your intention to apply, by contacting the subject supervisor: Agata.Zykwinska@ifremer.fr

In paralell, please submit your application to the doctoral school: VAAME (https://theses.doctorat-bretagneloire.fr/).

Doctoral students' contracts will start as of October 1st, 2024, subject to the submission of administrative documents authorizing Ifremer to recruit the doctoral student (certificate of completion of the Master 2 or engineering degree + visa for foreign doctoral students outside the EU).

The Institute and the recruiting departement

A pioneer in ocean science, IFREMER’s cutting-edge research is grounded in sustainable development and open science. Our vision is to advance science, expertise and innovation to:

- Protect and restore the ocean

- Sustainably use marine resources to benefit society

- Create and share ocean data, information & knowledge.

With more than 1,500 personnel spread along the French coastline in more than 20 sites, the Institute explores the 3 great oceans: the Indian, Atlantic and Pacific oceans. A leader in ocean science, IFREMER is managing the French Oceanographic Fleet and its dedicated scientists create ground-breaking technology to push the boundaries of ocean exploration and knowledge, from the abyss to the atmosphere-ocean interface.

Well-established in the international scientific community, our scientists, engineers and technicians are committed to advance knowledge about our planet’s last unexplored frontiers. They provide the science we need for informed decision-making and public policy and they transfer this knowledge and technology to businesses to fulfill public and private needs. Core to our mission is also to strengthen public awareness about the importance of understanding the ocean and its resources, and empowering future generations of leaders through education and outreach national campaigns.

Founded in 1984, IFREMER is a French public organization and its budget approximates 240 million euros. It is operating under the joint authority of the French Ministry for Higher Education, Research and Innovation, the french Ministry of the Sea, the French Ministry for the Ecological and Solidary Transition, and the French Ministry of Agriculture and Food.

How to apply for this position

Deadline for applications: 15/05/2024

All applications are processed exclusively via our website. Interested candidates can apply by clicking the “Apply” button.