Basic Malaria Research

We acquire new functional and mechanistic insight into processes linked to the essential biology of malaria blood stage parasites. These parasite forms are responsible for all malaria-related morbidity and mortality as well as for the transmission of parasites between humans via the mosquito vector. We place particular emphasis on

  1. Investigating the molecular mechanisms underlying parasite-induced red blood cell remodeling, through which infected red blood cells adopt pathogenic traits
  2. Understanding the transcriptional and epigenetic mechanisms responsible for antigenic variation and sexual conversion, which facilitate chronic blood infection and parasite transmission, respectively; and
  3. The identification and characterization of parasite ligands required for red blood cell invasion and their cognate invasion-inhibitory antibodies.

We further engage in elucidating mechanisms of action of anti-malarial drugs and in identifying immunological response signatures associated with native and adaptive anti-malarial immunity in vivo.

Scanning electron micrographs of an erythrocyte and of erythrocytes infected with P. falciparum

Elucidation of the Dynamic Interaction Network of Exported Proteins in P. falciparum

In this projects we study the interaction network of exported proteins which is of crucial importance for the export of virulence factors to the surface of the infected host cells and for other modifications allowing the parasite’s survival in its host cell. We use state-of-the-art molecular-genetic and cell-biological methods and produce a substantial number of transgenic parasites. In these parasites we study the function of exported proteins in order to identify those interactions that are needed to elicit the most important modifications.

Link to Project

An immunofluorescence staining of a gametocyte - the sexual form of P. falciparum

MalCommit - Understanding Sexual Commitment and Early Differentiation of Malaria Transmission Stages

The project aims to understand the processes responsible for the differentiation of asexual malaria blood stage parasites into sexual forms. The anticipated results may open up new avenues for the development of transmission-blocking drugs and vaccines.

Link to Project

3D-structure of the protein CyRPA

Role of the Plasmodim Falciparum Protein CyRPA in Parasite Invasion of Erythrocytes

A reverse vaccinology approach has led us to the identification of the P. falciparum Cysteine Rich Protective Antigen (PfCyRPA). The protein forms together with PfRH5 and PfRipr a multiprotein complex crucial for erythrocyte invasion. We have determined the crystal structure of PfCyRPA and are using this and parasite inhibitory and non-inhibitory anti-CyRPA monoclonal antibodies as a basis for analyzing its function.

Day C.J et al. The essential malaria protein PfCyRPA targets glycans to invade erythrocytes. Cell Rep. 2024;43(4):114012. DOI: 10.1016/j.celrep.2024.114012

Freville A et al. Expression of the MSPDBL2 antigen in a discrete subset of Plasmodium falciparum schizonts is regulated by GDV1 but may not be linked to sexual commitment. mBio. 2024;15(5):e0314023. DOI: 10.1128/mbio.03140-23

Hellingman A et al. Next generation chemiluminescent probes for antimalarial drug discovery. ACS Infect Dis. 2024;10(4):1286−1297. DOI: 10.1021/acsinfecdis.3c00707

Voss T.S, Brancucci N.M. Regulation of sexual commitment in malaria parasites - a complex affair. Curr Opin Microbiol. 2024;79:102469. DOI: 10.1016/j.mib.2024.102469

Wyss M, Thommen B.T, Kofler J, Carrington E, Brancucci N.M.B, Voss T.S. The three Plasmodium falciparum Aurora-related kinases display distinct temporal and spatial associations with mitotic structures in asexual blood stage parasites and gametocytes. bioRxiv. 2024:2024.05.27.596013. DOI: 10.1101/2024.05.27.596013