Liver stage malaria - Investigating the interaction between the malaria circumsporozoite protein and host importin-α proteins

Busra Turan Chaymae Abouazza

Investigating the interaction between the malaria circumsporozoite protein and host importin-α proteins

Malaria is one of the ‘Big Four’ deadliest human-infectious disease and is transmitted by the female
Anopheles mosquito. This disease is caused by parasites from the Plasmodium genus. The lifecycle starts
with the presence of sporozoites (SPZs) in the bloodstream of the human host as a result of a bite from
an infected mosquito. These SPZs can then reach and enter the liver cells through the interaction
between one of their major surface proteins, the circumsporozoite protein (CSP), and the highly sulfated
heparan sulfate proteoglycans on the liver cells. It is speculated that, once inside the liver cell, CSP can
enter the cytoplasm and possibly prevent the transport of some transcription factors to the nucleus of the
liver cell. This may result in the dampening of the inflammatory responses and thus promote the survival
of the parasite. Once the parasite reaches the blood phase, symptoms such as the characteristic fever
attacks can occur. It is important that malaria is treated properly and on time to prevent further
complications. Chloroquine- and artemisin-based therapies can be used as treatment. However, the
increasing resistance against these treatments is a motive to find new ways to combat or treat malaria.
The aim of this thesis was to investigate whether there is an interaction between the importin-α proteins
and the CSP of both P. falciparum and P. berghei. To achieve this, PfaCSPFL and PbeCSPFL were
recombinantly produced using E. coli cells and purified using chromatographic techniques. To obtain
both human and murine importin-α proteins, respectively HepG2 and Hepa1-6 cells were cultivated.
Finally, pull-down assays were performed to investigate whether there is a possible interaction between
CSP and importin-α proteins.


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Universiteit of Hogeschool
Master in de geneesmiddelenontwikkeling
Yann Sterckx
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