Recipient Organization
CORNELL UNIVERSITY
(N/A)
ITHACA,NY 14853
Performing Department
Microbiology And Immunology
Non Technical Summary
Theileriosis is a tick borne disease of livestock that results significant mortality and economic loss amounting to some $800 million worldwide. This disease is caused by infection by the intracellular parasite Theileria annulata, leading to an increase in white blood cells in infected cattle, with clinical symptoms of fever, anemia and jaundice. Theileriosis is fatal if left untreated. There is also emerging drug resistance in the parasite. Infected animals that recover can relapse, or act as carriers, which, in conjunction with ticks, maintain the continue presence of the parasite. Control of this infection is largely reliant on an attenuated vaccine that is not very effective, and also has problems such as cold chain and short-term protection. T. annulata infects white blood cells in cattle, and can lead to their continuous growth. Recent studies suggest that the Theileria parasite is able change specific signals inside the infected white blood cells in infected cattle to cause non stop growth of these cells, leading to the symptoms. However, we do not know whether these changed signals affect the parasite. This is a critical question given the emergence of drug resistance in this parasite, and the huge economic burden of this infection. This proposal seeks to get a better understanding of this process, which could result in better control of Theileriosis by understanding these pathways in cattle rather than parasite response, avoiding the development of drug resistance.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
The major goals of this project is to determine whether Theileria annulata infection hijacks host B lymphocyte signaling pathways leading to B cell lymphoma and enhanced parasite survival. Theileriosis is a tick borne disease of livestock that results significant mortality and economic loss amounting to some $800 million worldwide. This disease is caused by infection by the intracellular parasite Theileria annulata, leading to a lymphoproliferative disease, with clinical symptoms of fever, anemia and jaundice. Theileriosis is fatal if left untreated. There is also emerging drug resistance in the parasite. Infected animals that recover can relapse, or act as carriers, which, in conjunction with ticks, maintain the life cycle of the parasite. Control of this infection is largely reliant on an attenuated vaccine that is not very effective, and alsohas problems such as cold chain and short-term protection. T. annulata infects host lymphocytes, resulting in their transformation. Recent studies suggest that Theileria hijacks intracellular signaling pathways in infected host lymphocyte, resulting in this transformation. However, it is not clear whether these altered pathways have an effect on the parasite. This is a critical question given the emergence of drug resistance in this parasite, and the huge economic burden of this infection. A better understanding of this process could result in bettercontrol of Theileriosis by leveraging the host pathways rather than parasite response. There are 2 major goals for this project are:Goal #1: Determine the transcriptomic interaction between T. annulata infection and Bovine B lymphocytes. In this goal, we will utilize primary Theileria infected bovine B cells, to perform coupled RNA-Seq analysis of parasite and lymphocyte transcriptome so as to determine the profile of immune and parasite gene expression during infection.Goal #2: Determine the effect of anti-B cell lymphoma drugs on T. annulata/B cell transcriptome and response. In this goal, we will utilize anti-lymphoma drugs to inhibit B cell signaling pathways in Theileria infected bovine B cells, followed by analysis of parasite and B cell transcriptomes to determine the profile of immune and parasite gene expression when these pathways are disrupted.
Project Methods
The method for this proposal are:Specific aim #1:Determine the transcriptomic interaction between T. annulata infection and Bovine B lymphocytes.Here, we will utilize primary Theileria infected bovine B cells, to perform coupled RNA-Seq analysis of parasite and lymphocyte transcriptome to determine the profile of immune and parasite gene expression during infection. This data will be analyzed by standard bioinformation methods and results published for dissemination.Specific aim #2:Determine the effect of anti-B cell lymphoma drugs on T. annulata/B cell transcriptome and response.Here we will utilize small molecule anti-lymphoma drugs to inhibit B cell signaling pathways in Theileria infected bovine B cells, followed by analysis of parasite and B cell transcriptomes to determine the profile of immune and parasite gene expression when these pathways are disrupted. This data will be analyzed and results published for dissemination.