Impact of selective shedding of the endothelial glycocalyx on hemodynamics (M/F)

Job Description

Thesis Subject

The Marie Sklodowska-Curie GLYCOCALYX doctoral network (https://www.glycocalyx.org/) brings together 15 European partners implementing a multidisciplinary research and training program to study the self-organization and barrier functions of the glycocalyx.
Virtually all mammalian cells are covered with a dense and complex coat of sugar chains (glycans) known as the glycocalyx, which is essential for multicellular life. Glycocalyces accomplish critical functions in inter-cellular communication, controlling tissue development, homeostasis and repair, inflammatory and immune responses, neuronal connectivity, and symbiosis with bacteria. However, when dysregulated, they can promote immune diseases, neurodegeneration and cancer. Glycocalyces also act as the first line of defence against pathogens, but some pathogens have evolved to hijack the glycocalyx to promote infection.
Despite their importance, mammalian glycocalyces remain the 'dark matter' of biology, under-studied owing to the historical lack of preparative and analytical tools to probe the local molecular composition and transient interactions of molecules within glycocalyces, and missing physics rules to interpret experimental observations.
The GLYCOCALYX Network will train 15 PhD Fellows in physics, chemistry and biology methods and concepts required to resolve the dynamic organisation of glycocalyces. The project will establish a new level of understanding of how glycocalyces perform their many selective barrier functions. The PhD Fellows will receive cutting edge scientific training, alongside industry-relevant transferable skills, to equip them for careers in the medical technology sector and its underpinning research and innovations.


In the proposed PhD project, you will study the role of the main glycosaminoglycans in regulating the physical and mechanical properties of the endothelial glycocalyx, and how their selective degradation might impact the dynamics of flowing blood cells.
The endothelial glycocalyx (EG), which lines the lumen of blood vessels, is a key player in regulating interactions between circulating blood cells and the vessel walls. It is a micron-thick hydrated meshwork comprising glycosaminoglycans (GAGs), such as heparan sulfate (HS), chondroitin sulfate (CS) and hyaluronan (HA), as its main constituents. The loss of structural integrity and shedding of EG components are recognised to be associated with multiple acute or chronic vascular pathologies, and to affect hemodynamic features such as repulsion of red blood cells by the vessel walls or adhesion of immune cells.
However, the respective role of HS, HA and CS in controlling near-wall haemodynamics is not well understood, and whether they act synergistically to control EG properties and functions is essentially unknown.
You will address these questions by performing in vitro experimental studies using endothelialised microfluidic devices developed in our lab. Specific aims are: 1) Assess the GAG composition of the glycocalyx expressed by endothelial cells cultured under physiologically relevant shear flow; 2) Evaluate the impact of selective enzymatic degradation of the three main GAGs on glycocalyx thickness; 3) Study how such selective shedding affects elastohydrodynamic and adhesive interactions between the endothelium and circulating blood cells; 4) Assess how the mechanical properties of the EG control such interactions. The project will combine glycocalyx cell models, microfluidics, dynamic optical microscopy, glycocalyx labelling and GAG enzyme biochemistry.
The overall aim of the project is to define how the main GAGs regulate endothelial glycocalyx physical properties, and their specific roles in controlling haemodynamics. This will increase our fundamental understanding of glycocalyx functions, and potentially guide therapeutic efforts based on glycocalyx regeneration.
You will interact and develop research collaborations with our GLYCOCALYX academic and industrial partners, and in addition you will participate in activities of the Doctoral Network, including attending training courses and work placements at other sites.

Your Work Environment

-The project will take place at the Laboratory for Interdisciplinary Physics (LIPhy) in Grenoble. You will work in a multidisciplinary environment and interact with soft matter physicists and cell biologists in the lab. While the project is based in Grenoble, secondments in other laboratories of the network are planned.
Grenoble is the largest 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 about 200 researchers in soft matter physics, biophysics, physico-chemistry, biology and optics.


We are looking for an enthusiastic and rigorous experimentalist with a background in cell biology or in soft matter physics, with solid experimental skills and a keen interest in multidisciplinary work. Experimental work will include cell biology, microfluidics and microscopy. Previous experience in one of these fields will be appreciated, good experimental skills in general and a taste for meticulousness are essential. In parallel, interest for soft matter concepts and modelling will be of help to interpret the data. Experience in data analysis is a plus.

In addition, the position is in a sector related to the protection of scientific and technical potential (PPST) and therefore requires, in accordance with regulations, that your arrival be authorized by the competent authority of the French Ministry of Higher Education and Research (MESR).

Compensation and benefits

Compensation

3400 € 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

The research professions