Antoine CLAESSENS

Information

Scientific interests and projects

How is the malaria parasite Plasmodium falciparum able to establish a chronic, asymptomatic infection in a human host? The GATAC-Malaria team is addressing this question using blood isolates collected in the field and Next Generation Sequencing technology.

The objectives of our team are to decipher cellular and molecular features related to two essential parasitic functions: host cell invasion and intracellular replication, with the aim of identifying novel therapeutic strategies. Our research is mainly focused on T. gondii, which is a relevant model for many features conserved throughout the phylum. We then extend our important discoveries to the malaria parasite. We use a broad array of cell biological and biochemical approaches, as well as cutting-edge molecular genetics and genome editing.

A major challenge for any malaria elimination campaign is Plasmodium falciparum asymptomatic infections, the hidden infectious reservoir. Nevertheless, these infections can provide useful information on the host-pathogen interactions over an extended period of time. Our lab strive to understand how P. falciparum parasites can survive in human chronic infections over the 6-month long dry season, using an already available collection of blood samples from a cohort of asymptomatic volunteers in The Gambia. To explore how the parasite senses its environment and adapt to it, we measure the parasite multiplication rate and sequence its transcriptome. Our novel protocol can sequence a whole transcriptome from as few as 1000 parasites. We will identify genes associated with seasonality using dry and wet season samples from The Gambia. In parallel, we focus on parasite antigenic variation by analyzing the dynamicity of the var gene transcription pattern.

In summary, we will advance our understanding of the parasite biology and discover key molecular drivers of asymptomatic infections, a critical step to enable the eradication of malaria.

Top 5 publications of the last 5 years

1. Claessens A, Adams Y, Ghumra A, Lindergard G, … Bozdech Z and Rowe JA (2012). Group A-like PfEMP1s mediate cytoadherence to human brain endothelial cells. Proc Natl Acad Sci USA. doi: 10.1073/pnas.1120461109

2. Claessens A, Hamilton W, Kekre M, Otto T, Faizullabhoy A, Rayner J, Kwiatkowski D (2014). Generation of antigenic diversity in Plasmodium falciparum by structured rearrangement of var genes during mitosis. PLoS Genetics. doi:10.1371/journal.pgen.1004812

3. Claessens A, Hamilton W, Otto T, Kekre M, Fairhurst R, Rayner J, Kwiatkowski D (2016). Extreme mutation bias and high AT content in Plasmodium falciparum. Nucleic Acid Research. doi: 10.1093/nar/gkw1259

4. Claessens A, Affara M, Assefa S, Kwiatkowski D & Conway D (2017). Culture adaptation of malaria parasites selects for convergent loss-of-function mutants. Scientific Reports. Joint corresponding author. doi: 10.1038/srep41303

5. Claessens A, Harris LM, Stanojcic S, Chappell L, Stanton A, Kuk N, et al. (2018) RecQ helicases in the malaria parasite Plasmodium falciparum affect genome stability, gene expression patterns and DNA replication dynamics. PLoS Genetics. doi: 10.1371/journal.pgen.1007490