Our studies are aimed at developing interventions against human malaria. Both by manipulating and examining the human malaria-parasite Plasmodium falciparum in culture, and by exploiting rodent malaria parasites (Plasmodium berghei, P. yoelii) in mice, mosquitoes and in vitro.Our main research themes are:
- Development of a malaria vaccine based on genetically attenuated parasites (read more ....)
- Identification and analysis of parasite proteins that are (putative) targets for subunit vaccines
- Identification and analysis of parasite proteins that are (putative) targets for drugs
- Analysis of parasite-host interactions involved in pathology and disease
Our research interests and areas of expertise are:
- Genetic modification of malaria parasites and post-genomic technologies to identify and validate new drug and vaccine targets
- Generation and analysis of genetically attenuated parasites
- Parasite-host interactions involved in pathology and disease
- Anti-malarial drug testing
The Leiden Malaria Group (LMRG) developed Plasmodium genetic modification in 1995 and continues to innovate and lead research into Plasmodium transgenesis. Gene deletion mutants generated have been used to analyze a wide range of parasite gene functions. In 2005 they were one of the first groups to create genetically attenuated parasites that could serve as a live-parasite vaccine against malaria. In addition to gene-deletion and disruption-mutants, LMRG has created a number of parasites expressing foreign ‘transgenes’ to create reference parasite lines including those expressing fluorescent, bioluminescent, OVA reporter proteins, which have proven to be valuable tools in dissecting parasite-host interactions at the cellular and molecular level and shared by many different labs world-wide. They have created over 160 transgene expressing mutants and have distributed various mutant- and transgenic lines to more than 50 groups across the world.
Recently, the LMRG applied their expertise of Plasmodium genetic modification to the human parasite P. falciparum (Pf) and developed a novel method to efficiently generate stable genetically modified Pf that are free of heterologous drug selectable markers facilitating sequential genetic modifications within Pf. This method is key in creating a genetically attenuated PfSPZ vaccine, developed in collaboration with Sanaria, which has gained regulatory approval and will be tested in volunteers in 2017. As with rodent malaria parasites the LMRG, has developed technologies to not only remove genes from the parasite genome but have also insert transgenes into the human parasite. Indeed, the LMRG have further refined the recently described Clustered Regularly Interspaced Short Palindromic Repeats CRISPR-Cas9 genetic modification method in P. falciparum to more rapidly create mutant (gene deletion and insertion) Pf parasite lines, free of genes encoding drug resistance proteins.