Mission and main activities
Active Bio-Gels in Motion: Unraveling anomalous transport of Nano-Objects
Description of the project:
This project will investigate how nanoscale extracellular vesicles travel through the extracellular matrix to deliver their cargo of proteins, DNA and RNA to target cells, within biological tissues. Its aim is to identify the physical mechanisms that let a vesicle cross the interstitial space of tissues, and to determine how cell contractions effectively pump the interstitial fluid through the extracellular matrix and how these flows assist vesicle transport.
The central paradox is that vesicles move through fibrous matrices whose pores are much smaller than the vesicles themselves. Since no active, ATP-dependent mechanism has been identified in the extracellular matrix, the only local energy source is cellular contractility.
Working Hypothesis
The extracellular matrix undergoes elastic and inelastic deformations over long distances, arising from its nonlinear microstructure and non-local constitutive laws. We therefore hypothesize that traction forces generated by cellular contractions in fibrous tissues facilitate vesicle transport.
We propose two potentially synergistic mechanisms:
- Local “zipping/unzipping” mechanism. A transient interaction between the vesicle surface and a filament of the extracellular matrix could locally and reversibly open the matrix pores, allowing the vesicle to pass before immediate resealing. This process, occurring without significant energetic cost, would depend on the chemical composition of the matrix, thereby promoting selective transport in specific regions of the tissue.
- Transport driven by induced interstitial flow. Vesicles may be advected by interstitial fluid flows generated by coordinated cellular contractions. Collagen networks, characterized by nonlinear mechanical properties, enable the propagation of long-range deformation fields. These features may promote both remote opening of the matrix network and the establishment of fluid flow through this poroelastic medium.
Supervisors: Giovanni Cappello and Mehdi Bouzid
Research fields: Bio-physics, mechanics, theoretical modeling
Doctoral school: Physics Doctoral School (Grenoble)
Desired profile and expected skills
Education, diplomas: The candidate must hold a Master’s degree (or equivalent) in Physics, Engineering or Biology. He should also have a strong interest in interdisciplinary work at the interface between physics and biology, and in combining theory and experiments.
Personal skills: This PhD position requires the ability to work in a research team, which means having autonomy on individual tasks and maintaining interactions for collaborative work.
Disciplinary skills, experience: Knowledge in the following areas would be appreciated: optical microscopy, cell culture, microfluidics, data analysis, programming, numerical simulation and theoretical modeling.
Context and work environment
Team description: The PhD will take place within two Tec21 labs located on the Grenoble Campus:
- Experiments will be carried out in the team MicroTiss (LIPhy). Giovanni Cappello in an experimental bio-physicists, interested in the emergent behaviors of multicellular systems. He will coordinate the experimental program together with Claude Verdier, building on successful achievements on cell-ECM interactions.
- Theoretical modeling and simulations will be carried in the teams CoMHet (3SR) and MC2 (LIPhy). Mehdi Bouzid (3SR) is a computational and theoretical physicist expert of the physics and mechanics of (bio)-gels. He will co-supervise the PhD student and coordinate the theoretical aspects of the project, with P. Recho (LIPhy).
This recruitment takes place within the PhD@Tec21 Programme, which is co-funded as part of the Marie Skłodowska-Curie COFUND actions under the grant agreement #101217261. The recruitment process follows a specific selection and evaluation procedure with particular eligibility criteria, all of which are detailed in the applicant guide available on PhD@Tec21 Website.
Employment benefits and conditions
Université Grenoble Alpes (UGA) is offering a 36-month full-time work contract.
In line with the European Commission rules for Marie Skłodowska-Curie grant holders, the remuneration will consist of a gross monthly salary of 2,650 EUR. The estimated net salary to be perceived by the PhD fellow will be between 2,050 and 2,150 EUR.
Benefits include:
- Access to a high-quality work environment, including a personal computer, scientific equipment and access to library and shared lab facilities
- Access to high-level scientific and inter-sectoral training through 120 hours of doctoral courses and workshops
- Opportunity for 2-month secondments at an academic institution or industrial partner during the 2nd year of the PhD
- A vast choice of networking events and activities within the PhD@Tec21 Programme and through the international network of MSCA fellows
- Access to the UGA International Student Office, to assist the PhD fellows in searching for accommodation in Grenoble and support with administrative issues including visas, health, bank accounts, etc.
- Visa fees and registration to the UGA Doctoral School are covered by PhD@Tec21
- 45 days of paid holidays
- Sick leave
- Parental leave
General information
Contact for the questions related to the position:
PhD@Tec21 Management Board: guillaume.chambon@univ-grenoble-alpes.fr / amelie.bataille@univ-grenoble-alpes.fr
