"With our research we hope to find new ways to enable a sustainable vaccination against malaria or efficient drugs against the parasite."
Health and medicine
An international research group led by cell biologist Volker Heussler from the University of Bern has identified hundreds of genetic weaknesses in the malaria parasite Plasmodium. These are possible targets for new drugs and vaccines which one day could eradicate the disease.
Malaria is transmitted by the bite of mosquitoes infected with the malaria parasite Plasmodium. The genome of the parasite – in other words the entire genetic material – is relatively small with about 5,000 genes. In contrast to human cells, Plasmodium parasites only have a single copy of each individual gene. If you remove a gene from the entire genome of the parasite, this thus directly leads to a change.
An international scientific consortium of 22 researchers headed up by Professors Volker Heussler from the Institute of Cell Biology (ICB) at the University of Bern and Oliver Billker from the Sanger Institute in Great Britain have taken advantage of this fact. For the first time, the researchers carried out a genome-wide gene deletion study on malaria parasites: They specifically removed over 1,300 individual genes, observed the effects during the entire life cycle of the parasite and were thus able to identify many new weaknesses in the pathogen. Their findings were published in the prestigious journal Cell.
To systematically analyze the large number of identified metabolic genes, the researchers from Bern joined forces with the team of Professor Vassily Hatzimanikatis from the EPFL in Lausanne and Professor Dominique Soldati-Favre from the University of Geneva to form the "MalarX" consortium, which is financially supported by the Swiss National Science Foundation. Using data of the malaria genome screen, the group at EPFL calculated models that show essential metabolic pathways of the parasite.
"Thanks to these models, it is now possible to predict which of the previously unexplored genes are vital for the parasite and are therefore suitable targets for malaria control," adds model expert Anush Chiappino-Pepe from the EPFL in Lausanne.
Some of these predictions were then experimentally confirmed by the Bern researchers in close collaboration with the group of Prof. Chris Janse at the Leiden University in the Netherlands. "The genome-wide screen with the corresponding metabolic models represents a breakthrough in malaria research," says Magali Roques from the team in Bern. "Our results will support many malaria researchers worldwide. They can now concentrate on essential parasite genes and thus develop efficient drugs and vaccines against various stages of the parasite's life," added Ellen Bushell, former scientist at the Sanger Institute.
"Malaria is still one of the most important infectious diseases in developing countries.
Despite great efforts in medicine and science, more than 400,000 people worldwide are still dying of malaria."
According to Volker Heussler, this research approach was only possible with a combination of the enormous sequencing and cloning capacities at the Sanger Institute and the extraordinary infrastructure at the ICB in Bern. All life phases of the malaria parasite are established at the ICB, something possible in very few other institutes worldwide. In addition, the ICB is equipped with an exceptional range of high-performance microscopes, which enable pioneering research on the various life cycle stages of the parasite. Thanks to these prerequisites, the laboratory of Volker Heussler has already published many internationally recognized studies on the early phase of parasite infection.