ESR9: Glyco-modulation of membranes to elucidate host-parasite interactions

Location: University of Copenhagen, DK

Supervisor: Prof Ola Blixt

All cells are covered with a coating of complex carbohydrates (the glycocalyx) and many viruses, bacteria and protein toxins produced by bacteria exploit this sugar coating as a means of binding to and entering their target cells. We will elucidate glycosylation patterns present on living cells such as the Red Blood Cell (RBC) surfaces participating in ligand-receptor bindings in pathogenesis of Malaria and Babesiosis (but not limited to). These two diseases caused by infectious parasites (P. falciparum, and B. divergens), transmitted by vectors (mosquitoes and ticks) can lead to severe cases of disease in human hosts, from which a significant number is lethal. Infected RBCs (iRBCs) express variant surface antigens (VSA) of the parasite that presumably adhere to the non-infected RBC glycocalyx enhancing egress and infectivity. These interactions form RBC aggregation structures known as rosettes, leading to disease symptoms. The RBC cell surface glycocalyx is complex and consist of a repertoire of Glycolipids, N-, and O-glycans at various densities. Altogether, it’s a challenging task to sort out specific interactions between infected and non-infected RBCs. To tackle this, we will develop an artificial structurally defined glycocalyx displayed on large cell-sized liposomes (GUVs) as an investigative tool to elucidate the lowest common denominator of the receptor-ligand interactions of P. falciparum and B. divergens. Preliminary data with this novel Glyco-GUV tool provides, for the first time, an opportunity to systematically investigate cell-surface receptor interactions on a cellular level. The work may spur to developments of novel multivalent inhibitory compounds as a potential therapeutic treatment. We will team up with established parasite expert partners from Karolinska Institutet and Lund University as well as the ETN project partners to accomplish this PhD project.

If you are an open minded person and interested in organic synthesis, biochemical assays and infectious diseases, you might want to apply for this PhD position and, if selected, take part of building up an interesting research project. More specifically your project can involve carbohydrate, lipid and peptide synthesis, compound characterization and analysis, microarray assays, microscopy, and interactions with biomembranes.

Applicants should meet the following eligibility criteria:

  • Have a Diploma and/or a Master Degree in chemistry, or a closely related subject.
  • Have less than 4 years research experience at the signature of the contract (measured from the time the Master’s degree has been obtained).
  • Not have a PhD already.
  • Not have resided or carried out main activity in the Denmark for more than 12 months in the last 3 years immediately prior to the reference recruitment date.
  • Excellent knowledge of the English language (spoken and written / proficiency level)
  • Training on required laboratory techniques will be provided through the synBIOcarb network. However, practical experience in organic synthesis and protein chemistry would be advantageous.

The ESR will be contractually employed by University of Copenhagen and will receive a Monthly Living Allowance plus a Mobility Allowance compliant with the applicable EC Marie Skłodowska-Curie Actions-ITN general conditions. 

Application procedure:

Candidates should submit a CV, cover letter and the names and contact details of at least 3 references by e-mail to olablixt@chem.ku.dk indicating reference ESR9 in the subject.

The deadline for application is 07/03/2019

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