application abstract): This award would support four years of research in a murine malaria system, in which the investigator would study the invasion of malaria parasite into erythrocytes (RBC), the most critical step in malaria pathogenesis. The short term goal of the investigator is to, under the tutelage of experts in malaria, cellular biochemistry and molecular biology, test the hypothesis that the murine Duffy glycoprotein is a receptor for the invasion of Plasmodium yoelii into RBC. Development of the most current technical skills, innovative thinking, and experience in the fields of erythrocyte receptors, structural proteins and malariology are also part of this goal. The long term goal is to build an independent research program, involving the study of the host cell: parasite relationships critical in the pathogenesis of malaria. A program such as this, combined with the applicant`s expertise in veterinary clinical pathology, will provide for the basic research training of veterinary pathologists, an area of critical need in colleges of veterinary medicine. The career development of the candidate will occur in an excellent intellectual environment associated with immunologists, parasitologists, molecular biologists, and a cellular biochemist. In the years of funding of this award, the investigator will audit courses, will spend time in the laboratory working independently under the guidance of three mentors, an advisory committee and a collaborator, and will also spend time in the laboratories of other more experienced researchers (John H. Adams, mentor, and James Bamburg, advisory committee). The clarification of the role of the Duffy glycoproteins in murine malaria infections, including its parasite ligand, will open avenues of investigation into prevention (vaccines) and/or reduction in morbidity and mortality, using a convenient, relatively inexpensive, and well-developed model of human malaria (the mouse model). The first specific aim will be to confirm that the Duffy glycoprotein is a necessary receptor for P. yoelii. The second specific aim will be to identify a P. yoelii protein that is the parasite ligand for Duffy. The third specific aim will determine whether small polymorphisms in the Duffy molecule are responsible for marked differences in P. yoelii susceptibility, as is seen in a congenic mouse model. The data generated from this proposal will be used to publish three manuscripts, and will form the basis for an R01 to be submitted in the third or fourth year of funding.
| Swardson-Olver, Christine J; Dawson, Tracey C; Burnett, Robert C et al. (2002) Plasmodium yoelii uses the murine Duffy antigen receptor for chemokines as a receptor for normocyte invasion and an alternative receptor for reticulocyte invasion. Blood 99:2677-84 |
