David R. Allred
Department of Infectious Diseases and Pathology
PO Box 110880
2015 SW 16th AV
Gainesville, FL 33611-0880
352-294-4136 or 294-4132 (labs)
- MS, Biology, Wayne State University, Detroit, 1978
- PhD, Cell Biology, University of California, Riverside, 1982
- Postdoctoral, University of Colorado, 1983-1986; University of Florida, 1986-1988
Honors and Awards
- C.E. Cornelius Young Investigator Faculty Research Award, University of Florida, 1990
- Outstanding Faculty Achievement and Performance Award, University of Florida 1995
- University of Florida Faculty Research Productivity Award, 1999
- Editorial Board, Molecular and Biochemical Parasitology, 2007
- Editorial Board, The Open Parasitology Journal, 2007
- Editorial Board, Eukaryotic Cell, 2008
Mechanisms of persistence in babesial parasites
The long-term goal of the Allred Laboratory is to find the means to protect animals and humans from parasitic infection. The approach we have taken is to try to decipher mechanisms used by blood-borne parasites to interact with their vertebrate hosts in order to establish and maintain infections. Our current primary focus is on mechanisms used by babesial parasites to survive and establish highly persistent infections in hosts that are immune to disease. We have chosen to make Babesia bovis our primary study target. B. bovis is a bovine parasite that causes a devastating acute disease but which goes on to establish a generally asymptomatic persistent infection lasting many years. During the persistent infection, B. bovis-infected red blood cells (IRBCs) carrying mature parasites sequester in the vasculature of the deep organs, and the surface of IRBCs becomes altered antigenically during parasite development. We have attempted to establish the bases for these behaviors. In the process, we have demonstrated these changes are due, at least in part, to the expression of the parasite-derived protein, VESA1, on the IRBC membrane surface. VESA1 undergoes rapid antigenic variation during the course of infection in an individual animal. We have subsequently demonstrated a connection between antigenic variation and sequestration, and the sensitivity of cytoadhesion to the presence of antibodies recognizing VESA1. The molecular genetic basis for antigenic variation in B. bovis is currently being pursued. To date, this has resulted in the identification and characterization of the ves multigene family comprised of ves1a and ves1b genes encoding VESA1a and VESA1b subunits, respectively. We have since determined that B. bovis employs “segmental gene conversion” to construct mosaic ves genes from bits of many ves genes. The variability in antigenicity and function that can be generated in this way is staggering, and helps to explain how this parasite successfully evades ongoing antibody responses targeting the IRBC. These results explain the logic behind the seemingly incongruous connection of adhesion with a structurally variant protein.
We are currently studying the molecular basis for regulation of ves gene expression, including cross-talk among ves loci around the genome. Moreover, we are collaborating on detection of the mechanisms enabling intracellular parasites to export proteins out into the infected host cell, as well as the enzymatic machinery required for gene conversion events in antigenic variation. In the near future we hope to use this information to devise strategies for identifying candidate anti-parasite drugs targeting these various functions.
- Jackson, A.P., Otto, T.D., Darby, A., Ramaprasad, A., Xia, D., Echaide, I.E., Farber, M., Gahlot, S., Gamble, J., Gupta, D., Gupta, Y., Jackson, L., Malandrin, L., Malas, T.B., Moussa, E., Nair, M., Reid, A.J., Sanders, M., Sharma, J., Tracey, A., Quail, M.A., Weir, W., Wastling, J., Hall, N., Willadsen, P., Lingelbach, K., Shiels, B., Tait, A., Berriman, M., Allred, D.R., and Pain, A. 2014. The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction. Nucleic Acids Research, doi:10.1093/nar/gku322.
Additional publications here