Studentship: The role of Meq protein in the pathogenesis of Marek’s disease
Lead Research Organisation:
The Pirbright Institute
Department Name: UNLISTED
Abstract
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Technical Summary
Marek's disease (MD) is a common lymphoproliferative disease of poultry caused by the highly contagious alphaherpesvirus Marek's disease virus (MDV). Because of its contagious nature, rapid onset, and persistence in both the host and environment, MDV is arguably one of the most economically important pathogens of poultry. More than 22 billion doses of vaccines are used annually in an attempt to control MD.
The major oncogene encoded by MDV is Meq (MDV EcoRI-Q). It is expressed during both latent and lytic replication and closely resembles the bZIP transcription factor family. We have carried out extensive studies on this protein demonstrating a number of critical interactions crucial for its oncogenic properties. For example, Meq can dimerize with itself or with c-Jun, for its DNA binding affinity and transcriptional function. Meq can also interact with the cellular protein CtBP which allows it access to host chromatin modifying factors, thus playing a role in epigenetic regulation. In collaboration with the Structural Biology group in Oxford, we are also trying to determine the crystal structure of Meq to understand the basis of interactions.
In this doctoral project, we want to extend these studies to examine the global interactions of Meq, and identify the larger protein complexes that Meq will be a part of. This project will investigate the Meq protein complexes using a variety of approaches including quantitative proteomics, Yeast-two-hybrid assays, immunoprecipiation and GST pulldown assays. Novel interacting proteins that are identified can then be investigated for their roles in oncogenesis using shRNA knockdown, transcriptional assays and Chromatin Immunoprecipiation.
The major oncogene encoded by MDV is Meq (MDV EcoRI-Q). It is expressed during both latent and lytic replication and closely resembles the bZIP transcription factor family. We have carried out extensive studies on this protein demonstrating a number of critical interactions crucial for its oncogenic properties. For example, Meq can dimerize with itself or with c-Jun, for its DNA binding affinity and transcriptional function. Meq can also interact with the cellular protein CtBP which allows it access to host chromatin modifying factors, thus playing a role in epigenetic regulation. In collaboration with the Structural Biology group in Oxford, we are also trying to determine the crystal structure of Meq to understand the basis of interactions.
In this doctoral project, we want to extend these studies to examine the global interactions of Meq, and identify the larger protein complexes that Meq will be a part of. This project will investigate the Meq protein complexes using a variety of approaches including quantitative proteomics, Yeast-two-hybrid assays, immunoprecipiation and GST pulldown assays. Novel interacting proteins that are identified can then be investigated for their roles in oncogenesis using shRNA knockdown, transcriptional assays and Chromatin Immunoprecipiation.
Planned Impact
unavailable