Artur SCHERF

Information

Scientific interests and projects

The ‘Biology of Host-Parasite Interactions (BIHP)’ Unit, led by Prof Artur Scherf (DRCE CNRS), comprises 4 groups with a research focus on malaria parasite virulence, pathogenesis, liver stage infection and host immune responses to establish the molecular and cellular bases of parasite strategies to successfully complete the life cycle. By integrating a novel humanized mouse model, a rodent malaria model and mosquitoes, our studies address key biological aspects of the different stages of the life cycle development of Plasmodium falciparum and P. berghei.

Activities of team members within ParaFrap:

SCHERF A. has spearheaded the discovery of gene regulatory mechanisms over more than two decades. A main focus is on epigenetic factors that control 3-D spatial organization, transcription and posttranscriptional control of gene regulation with a particular focus on antigenic variation. The team uses routinely a wide array of techniques in literally all stages of the parasite life cycle, including genome-wide approaches such as ChIP-seq and RNA/DNA-seq as well as targeted genome editing. More recently, the team has developed in collaboration with a medicinal chemist (P. Arimondo, Institut Pasteur), distinct epigenetic compounds that kill efficiently multidrug resistant P. falciparum including artemisinin resistant strains and are active against transmission stages. Validation of lead epigenetic compounds using P. falciparum and P. vivax liver stages including hypnozoites, infected mosquitoes and humanized mouse models is an ongoing activity.

MANCIO SILVA L. has a long-term interest in understanding the malaria parasite interaction with hepatocytes and the interventions needed to control malaria disease. She is using rodent malaria models, sophisticated human hepatocyte culture systems and live imaging approaches to study sporozoite invasion and development in hepatocytes with a focus on the role of distinct metabolic states of host cells in infection.

GARCIA S. has a strong expertise on humanized mouse experimentation and has improved this model for studies of P. falciparum with the potential to establish this new model to study P. vivax.

Top 5 publications of the last 5 years

1. Baumgarten S, Bryant JM, Sinha A, Reyser T, Preiser PR, Dedon PC, Scherf A. Transcriptome-wide dynamics of extensive m6A mRNA methylation during Plasmodium falciparum blood-stage development. Nat Microbiol. 2019 Aug 5. doi: 10.1038/s41564-019-0521-7.

2. Mancio-Silva L, Slavic K, Grilo Ruivo MT, Grosso AR, Modrzynska KK, Vera IM, Sales-Dias J, Gomes AR, MacPherson CR, Crozet P, Adamo M, Baena-Gonzalez E, Tewari R, Llinás M, Billker O, Mota MM. Nutrient sensing modulates malaria parasite virulence. Nature. 2017 Jul 13;547(7662):213-216. doi: 10.1038/nature23009.

3. MacPherson C. and A. Scherf. Protospacer Workbench: flexible guide-RNA design for CRISPR applications. Nat. Biotechnol. 2015 Aug;33(8):805-6. doi: 10.1038/nbt.3291. Epub 2015 Jun 29.3

4. Ghorbal M, Gorman M, Macpherson CR, Martins RM, Scherf A, Lopez-Rubio JJ. Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system. Nat Biotechnol. 2014 Jun 1. doi: 10.1038/nbt.2925

5. Zhang Q, Siegel TN, Martins RM, Wang F, Cao J, Gao Q, Cheng X, Jiang L, Hon CC, Scheidig-Benatar C, Sakamoto H, Turner L, Jensen AT, Claes A, Guizetti J, Malmquist NA, Scherf A. Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria. Nature. 2014 Jun 29. (Research Highlights in Nat. Reviews Microbiol) doi: 10.1038/nature13468