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Resolution of macro-molecular structure and function of membrane-bound proteins in malaria bij Københavns Universitet

Resolution of macro-molecular structure and function of membrane-bound proteins in malaria.

Background.

Malaria caused by Plasmodium falciparum infections results in over 400.000 deaths and 200 million clinical cases each year. Severe malaria is caused by the binding of parasite-infected red blood cells to receptors on endothelial cell and immune cells. By binding in the host´s microvasculature, the parasites escape splenic clearance and binding to immune receptors dampen immune cell responses. The binding of human receptors is mediated by variant protein families called PfEMP1 and RIFIN exported onto the surface of the infected red blood cell. Naturally acquired immunity s mediated by antibodies targeting PfEMP1 and RIFIN.

Aim

Our long term aim is to develop a vaccine inducing antibodies that block PfEMP1/RIFIN function or new drugs which can respore the down-stream pathogenic processes of PfEMP1/RIFIN to prevent development of malaria.

The specific aim of this project is to develop biochemical and cellular assays to explore and resolve the macro-molecular structure and function of PfEMP1 and RIFIN protein interaction with human receptors on endothelial and immune cells.

Methods

You will be designing and producing different types and variants of recombinant PfEMP1, RIFIN or human monoclonal antibody proteins as well as nanodiscs to study the molecular structure-function behind the human and parasite protein interactions leading to malaria or protection against malaria. You will be using a wide array of lab techniques, depending on your skillset and interest (e.g. protein expression, purification, biophysical and functional tests of proteins e.g. ITC, SPR, ELISA, structural biology, CryoEM). Results from these studies will be complemented by functional assays using parasite-infected red blood cells, binding to receptors on immune or endothelial cells.

The MSc project includes international collaborative activities and you will work closely with other members of our research team located at 11th floor at the Mærsk Building.

Here, you will also be part of a larger research team cluster and shared laboratory facilities known as Centre for Medical Parasitology at ISIM, SUND, KU. (https://cmp.ku.dk/research/teamdiscovery/).

Qualifications

We are looking for a Student of Biochemistry, Molecular Biomedicine or related disciplines with a keen interest in applied protein biophysics, protein functional studies, structural biology, - also students with interest in infectious disease, immunity and cell biology are welcome.

For more information, please contact

Thomas Lavstsen at thomasl@sund.ku.dk

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