Developing and applying new methods to understand blood stage growth in Plasmodium falciparum

*Plasmodium falciparum* parasites cause nearly half a million deaths from malaria each year. There is still no highly effective vaccine, and resistance has emerged or is emerging to all current drugs. All the pathology and symptoms associated with malaria are caused by the growth of these parasites inside human red blood cells. If the parasites are to survive and be successful, they must invade, grow and survive under diverse micro–environmental conditions within red blood cells. Understanding the *P. falciparum* genes that regulate these key developmental processes could lead to the identification of targets for new drugs. However, while sequencing efforts have led to a good understanding of the *P. falciparum* genome and how it evolves over time and space, a disconnect remains between the amount of genome sequence data and what exactly these genes do – the phenotype. This therefore underpins my PhD thesis with a major goal of bridging the gap in our understanding of gene function in *P. falciparum*. I have developed high–throughput approaches combining next generation sequencing, flow cytometry and cell sorting to develop assays to accurately phenotype key aspects of the parasite life cycle such as invasion, cell cycle progression, multiplicity of invasion and replication capacity. These assays have been applied to a panel of *P. falciparum* genes in which genes potentially involved in specific developmental transitions have been deleted and reveal new phenotypes not described elsewhere in malaria literature.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2022

Author dc:creator

• Muhwezi, Allan

Advisor dc:contributor.advisor

• Rayner, Julian

• CRISPR/Cas9
• High-throughput sequencing
• Malaria
• Phenotyping
• Plasmodium falciparum

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/bfc61ef0-fd55-4c6b-aec5-42679ba22752/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.104349

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/361580