Supervisory team
Nagasaki University
- Lead: Asst. Prof. Shinya Miyazaki (smiyazaki@nagasaki-u.ac.jp)
- Prof. Osamu Kaneko (okaneko@nagasaki-u.ac.jp)
LSHTM
- Asso. Prof. Robert Moon (Rob.Moon@lshtm.ac.uk)
Project
Plasmodium falciparum (P. falciparum) is a mosquito-transmitted pathogenic parasite that causes many infections and deaths in tropical countries. After inoculation by mosquitoes to humans, P. falciparum multiplies once in the liver cell, then repeatedly in erythrocytes. Some parasites in the erythrocytes differentiate into gametocytes, which are transformed into gametes in vector mosquitoes. Compared to the asexual blood stage, the biology of the sexual stage is poorly understood at the molecular level. To improve the malaria control strategy, a better understanding of the sexual stages is required.
While the parasite multiplies inside erythrocytes, some infected erythrocytes migrate from the peripheral blood to the microenvironment within the bone marrow, where they mature to gametocytes. The mature gametocytes migrate back into the peripheral blood and spread to other human hosts by mosquito. In the bone marrow, gametocyte maturation is speculated to occur by adhesion of Plasmodium-infected erythrocytes to human bone marrow mesenchymal stem cells (HBMMSCs). However, the parasite ligands involved in adhesion to the HBMMSCs have not been identified.
In this project, we aim to identify the parasite ligands required for the adhesion of infected erythrocytes using gene expression analysis, transgenic approaches, and a culture system of immortalised HBMMSCs. We have already developed a cytoadhesion assay using P. falciparum-infected erythrocytes and immortalised HBMMSCs. This research will provide clues for answering the question, "How does P. falciparum survive and differentiate in the human bone marrow?" This research will reveal new host-pathogen interactions, leading to the development of new transmission inhibitors with a mechanism of action that inhibits the adhesion of infected erythrocytes to bone marrow cells.
The role of LSHTM and NU in this collaborative project
Selected students will stay in Nagasaki most of the time and conduct research under active supervision by Dr. Miyazaki and Prof. Kaneko. The student will visit London occasionally and conduct some experiments which may include design and generation of complex conditional knockout parasite lines, live cell imaging of P. falciparum parasite and expansion microscopy.
Particular prior educational requirements for a student undertaking this project
Basic knowledge of molecular biology and skills such as PCR is appreciated. Cell culture experience (aseptic technique) is also appreciated, but this is not an absolute necessity.
Skills we expect a student to develop/acquire whilst pursuing this project
- Skills in culturing malaria parasites and human cell lines, transfection and genome editing techniques (CRISPR/Cas9), and other advanced molecular biological techniques.
- Analysis of RNAseq expression data.
- Ability to critically discuss complex ideas based on a deep understanding of malaria cellular and molecular biology.