Research Activities

Malaria-derived Exosomes

SEM of Pf exosomes

The ability to communicate is essential for all living cells. Modes of communication include direct cell-to-cell contact and release of extracellular vesicles (EVs). EVs are commonly classified according to their mode of biogenesis. Exosomes are small vesicles (50-200nm in diameter), formed inside multivesicular bodies and secreted independently of cell death. They carry cargo of proteins, lipids, metabolites and nucleic acids, and fuse with distal cells providing a secure and efficient mode for delivery of signals. Due to their stability, exosomes protect their cargo against degradation and denaturation in the extracellular environment.
In this new area of malaria research, little is currently known about the exosome cargo and the precise mechanism of exosome cargo loading, delivery and function. We aim to gain a better understanding on how the parasite sorts its cargo and releases it, as well as investigating its function as effector in the extracellular milieu (or in the recipient cell). The advanced-nano approaches developed in our lab not only yield significant information on one of the most lethal human pathogens, but will further lead to important advances in the field of exosome research more broadly.

 

On picture: SEM of Pf exosomes

 

Parasite to Parasite Networking

Cell-cell communication offers an efficient strategy to coordinate cellular and social activities and has to be tightly regulated within a population. Malaria parasites must send extracellular factors in order to facilitate their development and survival. In our laboratory we venture beyond the comfort zone to study what molecular messages that these intracellular parasites exchange. We combine cell-communication methodologies in conjunction with molecular biology techniques to investigate this mysterious malaria parasite.
Malaria kills up to half a million people worldwide annually, especially children under 5 years of age. Improving our knowledge of how these parasites survive, proliferate and undergo interspecies transmission is critically important. To date, there is no effective vaccination available and there is an alarming rise in resistance to all commercial anti-malarial drugs. Discoveries of novel tracks for drug and vaccine development are essential for fighting malaria.

Parasite to Host Communication

Pathogens secrete factors to manipulate their hosts by diverting host pathways to facilitate infection. Malaria parasites are masters of their own survival, capable of drastic changes during their lifecycle. While it is clear that sophisticated strategies of Plasmodium sensing and manipulation of their hosts exist; their nature and activity remains largely unknown. Our preliminary results suggest that malaria parasites produce “armed exosomes” to deliver molecules harboring potential signals for modulating host target cells.
In our laboratory we begin to unravel the complex mutual interactions between Plasmodium falciparum and their hosts. We use imaging, molecular genetics, biochemistry and cell biology approaches to investigate different host responses.