PhD offer : cell adhesion at a soft interface through multivalent interactions

3 May 2024
Job Information

Organisation/Company

LIPHY UMR5588 CNRS Univ. Grenoble Alpes

Research Field

Physics » Biophysics

Researcher Profile

First Stage Researcher (R1)

Country

France

Application Deadline

1 Jul 2024 - 12:00 (Europe/Paris)

Type of Contract

Temporary

Job Status

Full-time

Hours Per Week

38,5

Offer Starting Date

1 Oct 2024

Is the job funded through the EU Research Framework Programme?

Not funded by an EU programme

Is the Job related to staff position within a Research Infrastructure?

No

Offer Description

The project is a collaboration between the Laboratory for Interdisciplinary Physics (LIPhy) and the Molecular Chemistry Department (DCM) aiming to understand physical cues of cell adhesion to a soft surface.

Scientific description

Most biological adhesive interactions are mediated by macromolecules that create a soft layer between two cells, or a cell and a cell layer. Examples include bacterial or parasite adhesion onto tissues, or blood cell or metastatic cancer cell adhesion to the blood vessel wall. Interestingly, cell adhesion is a finely regulated, critical process, but often through limited changes in the density or properties of adhesive molecules.

The aim of this project is to study and model key aspects of cell adhesion across a soft interlayer using soft matter and polymer physics concepts. In particular, the PhD focusses on understanding how softness of the adhesive surface and multivalent interactions (i.e., several receptors interact with several ligands, giving rise to entropic adhesive contributions) combine to finely regulate cell adhesion based on limited changes in receptor densities or affinities, a concept known as 'superselectivity'.

To achieve this goal, the first part of the PhD will build on the well-established experimental know-how at the Lab. for Interdisciplinary Physics and the Molecular Chemistry Department, in collaboration with the University of Leeds, to create an in vitro platform to study how cell mimetics adhere to model macromolecular layers as a function of their softness and of the receptor/ligand interactions. Establishing this platform also raises interesting polymer physics questions that will provide a first introduction to the soft matter theories that will be useful to the project.

In a second part, adhesion assays will be coupled to physical modelling to understand the key features that control cell adhesion to a soft layer. The coupling between layer softness and multivalency will be the focus of the experimental work and modelling.

Finally, this in vitro approach will be illustrated on the model cases of leukocyte adhesion to the vessel wall and of Toxoplasma gondii adhesion to intestinal cells (collaboration with the Institute for Advanced Biosciences).

[1] Davies et al, “An integrated assay to probe endothelial glycocalyx-blood cell interactions under flow in mechanically and biochemically well-defined environments”, Matrix Biology 78, 47 (2020)
[2] Dubacheva et al, “Designing multivalent probes for tunable superselective targeting”, PNAS 112, 5579 (2015)
[3] Dubacheva et al, 'Controlling Multivalent Binding through Surface Chemistry: Model Study on Streptavidin', JACS 139, 4157 (2017)
[4] Vigetti et al, “Coupling tunable surface chemistry with cell imaging identify GAG as sufficient ligand to guarantee minimal apical adhesion for high-speed gliding of the Toxoplasma parasite”, in revision in Nature Microbiology
[5] Davies et al, “Elastohydrodynamic lift at a soft wall”, Physical Review Letters 120, 198001 (2018)
 
Scientific environment
 
Grenoble is a pleasant city in the French Alps. It is one of the most renowned scientific areas in France, providing a vibrant and collaborative scientific environment.
The Laboratory for Interdisciplinary Physics (LIPhy) at the Grenoble Alpes University brings together researchers in soft matter physics, biophysics, physico-chemistry, biology and optics, while the Department de Chimie Moléculaire has world-renowed skills in sugar and polymer chemistry. Both labs are widely international.
The successful applicant will be hosted in the research group Mechanics of Cells in Complex Media (MC2). He/she will work under the supervision of Dr. Delphine Débarre (LIPhy) and Dr. Galina Dubacheva (DCM).
 
This project is a collaboration with the Richter group in Leeds (UK), with whom both supervisors share string ties (including previous co-supervision of students). Secondments in Leeds will be planned based on the advancement of the project so that the student experiences different lab culture and an international environment.
Requirements

Research Field

Physics » Biophysics

Education Level

Master Degree or equivalent

Skills/Qualifications

We are looking for an enthusiastic and rigorous experimental physicist or physico-chemist with a keen interest in multidisciplinary work. The work will be divided between experiments and subsequent modelling. Surface (bio)functionalization will be key to the success of the project: while no previous experience in the field is required, good experimental skills in general and a taste for meticulousness are essential. In parallel, interest for soft matter concepts and modelling will be essential to interpret the data. Experience in data analysis (including programming) is a plus.
The working language of the team is English: a good level is required, as well as good communication skills to ensure efficient collaboration between the labs.

Specific Requirements

Please send inquiries and meaningful applications (CV, publication list, a brief motivation letter, and contacts for references) until 01 July 2024 to: [email protected]

Languages

ENGLISH

Level

Excellent

Additional Information
Benefits
Gross salary (net salary about 20% less) : 2135,00 €/month
 
A package for funding the PhD research and dissemination (articles, conferences) is included in the grant and will cover all work-related expenses required during the PhD.
Eligibility criteria

Both labs are under national security procedures and the candidate will have to be approved by the French Research Ministry.

Work Location(s)

Number of offers available

1

Company/Institute

Lab. for Interdisciplinary Physics

Country

France

City

Grenoble

Postal Code

38402

Street

140, rue de la Physique

Geofield

Where to apply

E-mail

[email protected]

Contact

State/Province

Isère

City

St Martin d'Hères

Website

https://www-liphy.univ-grenoble-alpes.fr

Street

140 rue de la Physique

Postal Code

38402

E-Mail

[email protected]

STATUS: EXPIRED