CRISPR/CAS9 genetic modification of plasmodium falciparum and transgenic parasites in malaria vaccine research

Leiden Repository

CRISPR/CAS9 genetic modification of plasmodium falciparum and transgenic parasites in malaria vaccine research

Type: Doctoral Thesis
Title: CRISPR/CAS9 genetic modification of plasmodium falciparum and transgenic parasites in malaria vaccine research
Author: Marin Mogollon, C.Y.
Issue Date: 2018-11-28
Keywords: Plasmodium falciparum
Crispr/Cas9
Reporters
Transgenes
Chimera
Fertilization
Abstract: For rodent malaria parasites the availability of a variety transgenic parasite lines expressing different reporter proteins under the control of stage-specific or constitutive promoters have been of great benefit to studies to reveal parasite gene function and to studies focussed on the evaluation of novel drugs and vaccines. The availability of similar transgenic P. falciparum reporter lines would also help to advance gene-function studies and studies aiming at development of new therapies for P. falciparum parasites. In this thesis, we describe a set of studies performed in P. falciparum to develop novel CRISPR/Cas9 methodologies to improve P. falciparum transgenesis and to create novel transgenic parasites that can be used to analyse host-pathogen interactions and for anti-malarial drug and vaccine research. We describe studies aiming at improving CRISPR/Cas9 genetic modification for introduction of transgenes into the genome of P. falciparum using a ‘neutral’ locus, a disruption of the P230p gene using CRISPR/Cas9 showed that P230p like P230 and P48/45, has a vital role in P. falciparum male fertility and zygote formation and the creation of two chimeric P. falciparum parasites (Pf-PvCSP), where the gene encoding circumsporozoite protein (CSP), was replaced by two csp gene variants (VK210 and VK247) showing that species-specific features of CSP govern full sporozoite development.
Promotor: Supervisor: Yazdanbakhsh M. Co-Supervisor: Khan S.M., Janse C.J.
Faculty: Faculty of Medicine, Leiden University Medical Center (LUMC)
University: Leiden University
Uri: urn:isbn:9789461829191
Handle: http://hdl.handle.net/1887/67294
 

Files in this item

Description Size View
application/pdf Full Text 86.90Mb View/Open
application/pdf Cover 970.9Kb View/Open
application/pdf Title Pages_Contents 81.42Kb View/Open
application/pdf Chapter 1 2.265Mb View/Open
application/pdf Chapter 2 6.342Mb View/Open Full text at publisher site
application/pdf Chapter 3 6.866Mb View/Open Full text at publisher site
application/pdf Chapter 4 764.2Kb View/Open Full text at publisher site
application/pdf Chapter 5 403.0Kb View/Open
application/pdf Chapter 6 875.8Kb View/Open Full text at publisher site
application/pdf Chapter 7 109.5Kb View/Open
application/pdf Summary in Dutch 77.61Kb View/Open
application/pdf Summary in English 78.46Kb View/Open
application/pdf Acknowledgements_Curriculum Vitea_Publications 82.00Kb View/Open
application/pdf Propositions 408.4Kb View/Open

This item appears in the following Collection(s)