Anti-malaria target and lead compounds, identification and validation

Coordinator:    Dr.Birte Sönnichsen
Institution: Cenix BioScience GmbH
Building on the prototypic platform and proof of concept data, Cenix will further develop its existing cell-based HT/HC screening platform for liver stage Plasmodium infection to enable two key applications:
first, target identification by genome-scale RNAi screening, and
second, identification and optimisation of lead compounds through cell-based screening of small synthetic molecule libraries.

In particular, the following key aspects are going to be improved:

o Throughput: 384well and 1536well plate formats

o Robustness and reproducibility of the screening assay: handling of parasites, infection protocol, image analysis (supported by all three academic labs)

o Medical relevance of the screening assay: explore the use of other cell lines/primary hepatocytes in combination with P. falciparum to replace currently used model parasite P. berghei (supported by Mota and Matuschewski labs), set up secondary microscopy based assays (supported by Frischknecht lab)

In addition, Cenix will continue lead compound optimisation on the ScarB1 inhibitors through screening customised, focussed compound libraries, followed by SAR analysis. The Mota lab will continue to support Cenix with their expert knowledge on the parasite, and in particular for validation studies on host cell factors required for infection. In detail, they will carry on elucidating the role of ScarB1 and future new targets, and help Cenix to define a prophylactic window for lead compounds identified in previous and future screens through in vivo testing in mice.

Further Coordinators:
INTRANET (Members login)