Marie Skłodowska-Curie Doctoral Network Researcher

Applicants are invited to apply for a Researcher (Research Assistant Level) position to work in the Marie Skłodowska-Curie Doctoral Network GLYCOCALYX. 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.

The glycocalyx acts as a selective barrier that viruses and other biological entities like proteins and bacteria need to pass to reach the cell surface. In terms of physical interactions, a repulsive term arises from the need to penetrate through the dense glycocalyx polymer brush, while attraction is dictated by the various transient, reversible bonds formed by (viral) receptors and their cognate ligands, the latter constituted by specific glycans in the glycocalyx (e.g., sialic acids for influenza virus). This physical picture qualitatively illustrates that the free-energy profile that a ‘biocolloid’ (virus, protein or bacteria) encounters on its approach to the cell surface will depend on the structure of the glycocalyx and the corresponding multivalent presentation of ligands. Knowledge of this free-energy profile can be used to quantitatively link the chemistry and structure of the glycocalyx to the kinetics of attachment to the cell, and thus mechanisms such as viral infectivity.

As an MSCA PhD Fellow at Imperial, you will develop new computational models to determine the biocolloid/glycocalyx free-energy profile but also use AI-based approaches to design systems to experimentally probe, or even modify, such profile and its associated properties. The end goal is to unravel the molecular determinants of attachment and transport through the glycocalyx and exploit this knowledge for the design of biomedical applications. In order to achieve this goal, you will also 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.

You should have a good master’s degree in a subject related to physical, biophysical, computational physics, statistical physics, soft matter and polymer physics, materials, bioengineering, physical chemistry, or biological engineering.

The position requires the candidate to meet the academic requirement to register for a PhD at Imperial College London. At the date of recruitment, the candidate must not already be in possession of a doctoral degree. The applicant must not have resided or carried out their main activity (work, studies etc.) in United Kingdom for more than 12 months in the past three years.