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SUMMARY:Cutting back malaria: CRISPR-based approaches for antimalarial tar
 get discovery - Professor Marcus Lee - Biological Chemistry and Drug Disco
 very\, University of Dundee
DTSTART:20240320T140000Z
DTEND:20240320T150000Z
UID:TALK207331@talks.cam.ac.uk
CONTACT:Anna Protasio
DESCRIPTION:The repeated emergence of antimalarial resistance underscores 
 the importance of identifying new drug targets\, as well as understanding 
 the genetic architecture of current resistance pathways and any associated
  fitness costs. We have developed several genomics-based approaches that l
 everage CRISPR editing of the _Plasmodium falciparum_ genome to validate c
 ausal resistance mutations and explore the essentiality and biological fun
 ction of gene families as antimalarial targets. To more efficiently determ
 ine if compounds kill the parasite via known modes-of-action\, we have gen
 erated a panel of barcoded parasite lines that encompass a wide spectrum o
 f the known _Plasmodium_ resistome\, and have miniaturised a compound-scre
 ening assay to allow semi-automated liquid handling of parasite cultures. 
 Competitive growth of drug-resistant lines also reveals the fitness cost o
 f resistance. To overcome a bottleneck in evolution of resistance in the l
 ab\, we have also developed “mutator” parasite lines with an elevated 
 mutation rate to increase the genetic complexity of parasite cultures. Fin
 ally\, we are exploring whether non-coding mutations\, specifically in lnc
 RNAs\, might also contribute to the parasite resistome. Collectively these
  approaches aim to accelerate the identification and validation of potenti
 al new targets\, as well as understand the breadth of the parasite respons
 e to antimalarial challenge. 
LOCATION:Seminar Room\, Tennis Court Road\, Dept of Pathology.
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