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University of Cambridge

1. Lin, Yen-Chun. Static and Microfluidic Live Imaging Studies of Plasmodium falciparum Invasion Phenotypes .

Degree: 2018, University of Cambridge

Severe malaria caused by it{Plasmodium falciparum} (it{P. falciparum}) remains a leading cause of death in many low and middle income countries. The intraerythrocytic reproduction cycle of the parasite is responsible for all the symptoms and mortality of malaria. The merozoite, first invade a red blood cell (RBC) in the circulation, then grows, develops and multiplies within it by clonal division. Merozoite invasion is a complex process involving dynamic interactions between ligands in the merozoite coat and receptors on the red blood cell membrane. Therefore, filming the complete malaria invasion processes may shed the light on its mechanism. The rationale of this work is that learning how the various ligand-receptor interactions affect invasion phenotypes will lead us to a better understanding of the key biological and biophysical aspects of parasite growth in the blood. \ The work described has firstly involved the development of an optimised imaging platform for recording egress-invasion sequences. I used live cell microscopy to understand this stage of malarial infection better, by monitoring egress-invasion sequences in live cultures under controlled conditions and addressing the morphology and kinetics of erythrocyte invasion by it{P. falciparum}. In addition, the erythrocyte invasion phenotypes of the various it{P. falciparum} strains were systematically investigated for the first time by live cell microscopy. Furthermore, to better understand genetic recombination affecting erythrocyte invasion phenotypes, progeny from the 7G8 x GB4 cross was compared to their parents. In order to investigate specific receptor-ligand interactions and their distinct functional characterisations at each distinct stage, the enzymes that cleave receptors on the erythrocytes and antibodies targeting ligands on the merozoites were studied and their effects observed using the live-imaging platform. In the results, the functions of ligands on the merozoites demonstrated for the first time distinct and sequential functions of proteins during erythrocyte invasion, which could potentially guide the design of more effective malaria vaccines. \ In addition, I have designed microfluidic devices for studying blood stage malaria. Polydimethylsiloxane (PDMS) microfluidic devices are optically transparent, non-toxic and have biocompatible features. Building on previous work, I made specific microfluidic devices for achieving a high throughput of egress-invasion observations. Infected red blood cells were delivered into a microfluidic device channel containing cage-like "nests". The nests were designed to selectively trap these stiff, egress-ready cells, in order to obtain streams of merozoites on maturation. Uninfected RBCs were delivered from another input into a long serpentine channel co-flowing with the egressed merozoites. The results indicated that, during it{P. falciparum} erythrocyte invasion under flow conditions, the morphological effect on erythrocytes and the kinetic properties show…

Subjects/Keywords: Plasmodium falciparum; microfluidics; live-imaging; invasion phenotypes

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APA (6th Edition):

Lin, Y. (2018). Static and Microfluidic Live Imaging Studies of Plasmodium falciparum Invasion Phenotypes . (Thesis). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/271829

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Lin, Yen-Chun. “Static and Microfluidic Live Imaging Studies of Plasmodium falciparum Invasion Phenotypes .” 2018. Thesis, University of Cambridge. Accessed June 19, 2018. https://www.repository.cam.ac.uk/handle/1810/271829.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Lin, Yen-Chun. “Static and Microfluidic Live Imaging Studies of Plasmodium falciparum Invasion Phenotypes .” 2018. Web. 19 Jun 2018.

Vancouver:

Lin Y. Static and Microfluidic Live Imaging Studies of Plasmodium falciparum Invasion Phenotypes . [Internet] [Thesis]. University of Cambridge; 2018. [cited 2018 Jun 19]. Available from: https://www.repository.cam.ac.uk/handle/1810/271829.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lin Y. Static and Microfluidic Live Imaging Studies of Plasmodium falciparum Invasion Phenotypes . [Thesis]. University of Cambridge; 2018. Available from: https://www.repository.cam.ac.uk/handle/1810/271829

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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