Functional characterizations to model host-pathogen interactions during malaria transmission

Host competence in relation to infectious agents and vector-borne disease is one of mankind’s biggest challenges in today’s world where global warming is a fact and globetrotting is common practice. This project aims to increase our understanding of genetic factors underlying host and vector competence.

For this purpose, I will focus on the malaria parasite Plasmodium falciparum, which has a highly complex lifecycle and where transmission is strictly linked to sexual stage differentiation of a small subset of parasites called gametocytes.

Gametocytes home to and develop in the human bone marrow until they reach maturity, at which point they re-enter the blood stream ready to be taken up by a mosquito.

Development in the mosquito includes fusion and zygote formation prior to traversal of the midgut wallWe have recently generated several single-cell transcriptome data sets, which cover this entire developmental process both on the parasite and vector side.

Now we will use complementary genome editing strategies to enable modeling of host and parasite factors essential for the process of transmission.

In addition, we will utilize Spatial Transcriptomics to study P. falciparum gametocyte development in the bone marrow from non-human primates.

I anticipate that our findings will greatly contribute to our knowledge about genes and gene regulatory pathways relating to sexual cell fate and development in general and host-pathogen interactions during malaria transmission in particular