Exploration of the malaria parasite lifecycle stages and strains circulating in natural infections at single-cell resolution
type: CreativeWork
description: Malaria is still a major global public health problem, resulting in an unacceptably high annual mortality of over half million. Extensive diversity in malaria parasites is a key challenge in developing effective interventions. Many infections constitute several strains, and this complicates malaria studies since it is hard to disentangle strains using traditional bulk approaches. There are also parasites of different stages circulating in natural infections, but there is very limited understanding of these stages, especially gametocytes, which are overwhelmingly underrepresented in a typical infection. The recent development of single-cell RNA sequencing (scRNAseq) offers a great opportunity to study malaria parasites in natural infections and opens new avenues of exploration previously inaccessible to bulk approaches. In Chapter 1, I delve deeper into the motivations for using scRNAseq in natural infections and the general background knowledge on malaria infections and technologies necessary to contextualise my findings. I then detail my findings, some of which are novel, in the remaining chapters. In Chapter 2, I explore the stages circulating in asymptomatic infections, finding early asexuals and late gametocytes as previously observed. However, the high scRNAseq resolution reveals that the female and male gametocytes each constitute two transcriptomically distinct forms. One of the male and female gametocyte forms is characterized by low expression compared to the other male and female pair, and I label these as LE (low expression) gametocytes. I hypothesise that these are older, dormant gametocytes. In Chapter 3, I investigate strain dynamics in one asymptomatic infection. I estimate around eight strains in this infection and find that the distribution of strains in the asexual stage does not correlate with that in the sexual stage. Close relatedness patterns between the strains in this infection suggest that they were introduced by the same mosquito. Using thi…
abstract: Malaria is still a major global public health problem, resulting in an unacceptably high annual mortality of over half million. Extensive diversity in malaria parasites is a key challenge in developing effective interventions. Many infections constitute several strains, and this complicates malaria studies since it is hard to disentangle strains using traditional bulk approaches. There are also parasites of different stages circulating in natural infections, but there is very limited understanding of these stages, especially gametocytes, which are overwhelmingly underrepresented in a typical infection. The recent development of single-cell RNA sequencing (scRNAseq) offers a great opportunity to study malaria parasites in natural infections and opens new avenues of exploration previously inaccessible to bulk approaches. In Chapter 1, I delve deeper into the motivations for using scRNAseq in natural infections and the general background knowledge on malaria infections and technologies necessary to contextualise my findings. I then detail my findings, some of which are novel, in the remaining chapters. In Chapter 2, I explore the stages circulating in asymptomatic infections, finding early asexuals and late gametocytes as previously observed. However, the high scRNAseq resolution reveals that the female and male gametocytes each constitute two transcriptomically distinct forms. One of the male and female gametocyte forms is characterized by low expression compared to the other male and female pair, and I label these as LE (low expression) gametocytes. I hypothesise that these are older, dormant gametocytes. In Chapter 3, I investigate strain dynamics in one asymptomatic infection. I estimate around eight strains in this infection and find that the distribution of strains in the asexual stage does not correlate with that in the sexual stage. Close relatedness patterns between the strains in this infection suggest that they were introduced by the same mosquito. Using thi…
author: Rop, Jesse
language: eng
keywords: Lifecycle stages, Malaria, Mali, Natural infections, Plasmodium falciparum, single-cell RNA sequencing, Strains
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/a304ef30-958e-4849-b5f9-02c95f01eacb/download
license: https://creativecommons.org/licenses/by/4.0/
date published: 2024-12-31
date modified: 2026-07-22T22:24:06Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.119978