MSCA PhD Fellow (M/F) - Recognition and self-organisation of the fuzzy glycocalyx – Does binder clustering matter?

Job Description

Thesis Subject

Applications are invited for a 36-month PhD Fellow position at CNRS / Université Grenoble Alpes (UGA) as part of the Marie Sklodowska-Curie Doctoral Network GLYCOCALYX.

About the Network. GLYCOCALYX brings together 15 leading European partners in a transnational network, implementing a multidisciplinary and intersectorial research and training programme between the academic and industrial partners, to research the self-organisation and barrier functions of the mammalian 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 chemistry, physics 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.

About the PhD Project "Recognition and self-organisation of the fuzzy glycocalyx – Does binder clustering matter?"

As MSCA PhD Fellow at the Department of Molecular Chemistry (CNRS-UGA, Grenoble), you will develop synthetic glycocalyces with tunable binder affinity, density, and distribution, and use them to determine how binder and cross-linker valency govern superselective multivalent recognition and the physical properties of glycocalyx-like films.

Transient multivalent interactions are commonplace in glycocalyces. They control the recognition between the glycocalyx and signalling proteins, extracellular vesicles and pathogens (toxins, viruses), and also contribute to the supramolecular organisation of the glycocalyx itself (e.g., through macromolecular cross-linking). Multivalent interactions are inherently sensitive to the spatial disposition of binding sites, but how the distribution of binders affects glycocalyx recognition and self-organisation is not well understood. The complexity and poor control over the composition and organisation of cellular glycocalyces makes such studies challenging. The goal of this project is to elucidate how clustering of binders, as opposed to a homogeneous binder distribution, impacts glycocalyx recognition and physical properties.
This project will combine expertise in bioorganic synthesis, biomimetic surface design and advanced physicochemical characterization to develop new chemical tools to make designer glycocalyces. By confronting experimental data with theory and computer simulations (in collaboration with Network partners), it will define basic physical rules that predict how binder clustering affects glycocalyx recognition and self-organisation. The findings will provide a deeper understanding of multivalent interactions in 'fuzzy' glycocalyx systems, and may enable new routes to control glycocalyx interactions in biomedical applications.

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.

Required skills:
We are looking for an enthusiastic and rigorous experimental physico-chemist, biophysicist or soft matter physicist with solid experimental skills and a keen interest in multidisciplinary work. Prior experience in surface characterization techniques, biomolecular interaction analysis, surface functionalization, and/or bioorganic synthesis is essential. Candidates should also demonstrate a strong interest in interdisciplinary research at the interface of chemistry, physics, and biology. The position requires excellent written and oral communication skills, together with strong organizational abilities. Applicants should be able to manage their time effectively, meet deadlines, and handle competing demands in a responsible and autonomous manner. A proven ability to work both independently and as part of a team is also expected.
Training in the required experimental techniques will be provided within the host laboratory and through the GLYCOCALYX network. However, previous experience in the field of biointerfaces, as well as skills in programming and/or simulation, will be considered an asset. Likewise, experience contributing to publications in internationally recognized peer-reviewed journals, or evidence of research in progress with publication potential, will be appreciated.

To apply, please comply with the eligibility requirements for Doctoral Training Networks - MSCA Doctoral Networks, which can be found directly on https://marie-sklodowska-curie-actions.ec.europa.eu/actions/doctoral-networks

Your Work Environment

The work will be performed under the supervision of Dr G. Dubacheva in the I2BM team of DCM (Département de Chimie Moléculaire, CNRS-UGA). I2BM research focuses on the design of macromolecular architectures and functional interfaces for bioanalysis and therapeutic applications (https://dcm.univ-grenoble-alpes.fr/research/ingenierie-et-interactions-biomoleculaires). The candidate will be based Grenoble, with secondments in other laboratories of the network. 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 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

The gross salary is approximately €3400 per month, to which is added a mobility allowance of €710 per month and, where applicable, a family allowance.

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

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