Probing Mechanisms of P. falciparum Artemisinin Resistance Using Single-Cell Transcriptomics
Abstract
Artemisinin (ART) derivatives are highly potent anti-malarial drugs and are the main treatment option in most malaria-endemic regions across the globe. The emergence and spread of artemisinin-resistant parasites threatens reverse the recent gains in reducing malaria morbidity and mortality. Resistance is associated with mutations in the kelch13 gene (K13). K13 mutant ring-stages contain a sub-population able to survive ART exposure for a prolonged period and continues replicating once drug pressure is removed. Our ongoing experiments use single-cell transcriptomics (scRNAseq) to characterize unique patterns of gene expression within this survivor population that underlie their resistance phenotype. Subsequent experiments will then evaluate the function of the involved genes in artemisinin-resistance. Over the first 12 months of the project, 1. Ring-stage survival assays to measure ART resistance level of sensitive and K13 resistance mutants were successfully implemented. 2. scRNAseq equipment was successfully transferred from our previous collaborator and established in the lab. 3. Initial round of scRNAseq was carried out. 4. scRNAseq procedures were optimized for P. falciparum ring stages with substantial improvements in transcript capture. Unexpected personnel turnover and reagent quality issues resulted in unanticipated delays and a request for a 12-month no-cost extension was filed and approved.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2019
- Accession Number
- AD1080085
Entities
People
- Bjorn F. Kafsack
Organizations
- Weill Cornell Medicine