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Developing a humanized mouse model to study malaria vaccines
University of Alberta
Department of Pediatrics
Dr. Susan Gilmour
Dr. Michael Hawkes
Type of Research Project
- Basic science
What is the background of the project?
Description: Malaria remains a leading cause of death among children under 5 globally. Malaria vaccine development has been hampered by the lack of a rodent model to study responses to the human parasite Plasmodium falciparum. We have begun to optimize a humanized mouse model with xenotransplanted human hepatocytes and leukocytes, that will be capable of sustaining infection with liver stage P. falciparum. The mouse can also be stably xenotransplanted with human hematopoietic stem cells, allowing us to recapitulate human cell-mediated immune responses to the intra-hepatic parasite. This model, once optimized, will allow us to study the protective effect of novel pre-erythrocytic vaccine candidates against falciparum malaria. Aim: The aim is to develop a mouse model with humanized hepatocytes and hematopoietic cell lineage which faithfully recapitulates human cell-mediated responses to intracellular pathogens. Methods: Magnetic bead isolation of CD34+ stem cells from umbilical cord blood. Magnetic bead immune-separation of CD3+ T-cells from umbilical cord blood. Viability (trypan blue exclusion) of isolated cells. Flow cytometry characterization of isolated cells. Cryopreservation and biobanking of isolated cells. HLA-typing of isolated cells.
What is the aim of the project?
The aim is to develop a mouse model with humanized hepatocytes and hematopoietic cell lineage which faithfully recapitulates human cell-mediated responses to intracellular pathogens.
What techniques and methods are used?
Magnetic bead isolation of CD34+ stem cells from umbilical cord blood. Magnetic bead immune-separation of CD3+ T-cells from umbilical cord blood. Viability (trypan blue exclusion) of isolated cells. Flow cytometry characterization of isolated cells. Cryopreservation and biobanking of isolated cells. HLA-typing of isolated cells.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks of the student will be performed on his/her own
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student will be expected to generate a biobank of HLA-typed, cryopreserved stem cells and autologous T-cells derived from umbilical cord blood. Training will be provided for all steps in this protocol. For each cord blood donor, the student will collect umbilical cord blood from our research nurse. The student will purify the CD34+ stem cells and CD3+ T-cells from the blood using magnetic bead separation. The student will characterize the cells using flow cytometery and a viability assay (trypan blue exculsion). The student will HLA-type the cells. The student will cryopreserve the cells, maintaining a well-annotated registry of the biobank for future use of stem cells in humanized mouse experiments.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Previous web lab skills desirable. Knowledge in immunology desirable. Biosafety training and certification will be provided and is needed to work in the lab. No other limitations. No report needed after the exchange.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system
- Good MF; Hawkes MT; Yanow SK. Humanized Mouse Models to Study Cell-Mediated Immune Responses to Liver-Stage Malaria Vaccines. Trends Parasitol. 2015 Nov;31(11):583-94
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