Location: Animal Disease Research
Project Number: 2090-32000-040-019-T
Project Type: Trust Fund Cooperative Agreement
Start Date: Jul 5, 2019
End Date: Dec 31, 2023
Objective:
To identify and functionally characterize proteins that determine the growth, virulence, and pathogenicity of Babesia bovis and B. bigemina parasites. Specific aims:
1. Discovering and characterizing virulence-associated proteins in Babesia bovis and B. bigemina.
2. Generating and characterizing unique genetically-modified Babesia parasites that vary in their expression of the identified virulence-associated proteins.
3. Characterising the functional phenotypes of mutated parasites in vitro and in their natural host (cattle).
Approach:
Babesia are tick-borne protozoan parasites that cause significant economic losses to the livestock industry. It is estimated that ticks and tick-borne diseases cause annual losses of > U.S. $20 billion worldwide. In developing countries, the loss of livestock caused by ticks and tick-borne diseases result in increased poverty in rural areas where smallholder farms predominate. Currently, there are no effective vaccines that control tick-borne pathogens. More effective, safer and environmentally friendly approaches to control bovine babesiosis are desirable. New vaccine targets will be discovered by defining the repertoire of Babesia bovis and B. bigemina proteins expressed in the surface of infected erythrocytes and proteins expressed in the surface of free merozoites with a role in erythrocyte invasion. Proteins conserved among both parasites will be prioritized with the long term goal of developing a dual B. bovis and B. bigemina vaccine. The novelty of this proposal is the identification of novel conserved proteins that are central to the pathogenicity of Babesia parasites and determine their precise role in the disease process. The strategic advantage and novelty of the approach is also enhanced by our development of stable transformation systems to manipulate the parasites genome to create defined transgenic parasites and to express native-like antigens. Together with new bioinformatics approaches, state-of-the-art imaging as well as a suite of cellular and biophysical assays, this proposal is both, original, and at the cutting edge of internationally competitive.
