Molecular events and mechanisms of Marek's disease pathogensis

Lead Research Organisation: The Pirbright Institute
Department Name: Div of Immunology Compton

Abstract

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Technical Summary

Marek¿s disease (MD) is one of the most highly oncogenic herpesviruses known. The causative Marek¿s disease virus (MDV) is an alphaherpesvirus encoding more than 100 open reading frames. Molecular mechanisms of oncogenesis of MD are not fully understood. Among the different MDV-encoded genes, Meq gene, which has all the hallmarks of a potent oncogene, is considered to be the most important gene involved in oncogenesis. Although the molecular pathways of Meq-induced oncogenesis are not fully understood, it is believed that its properties of transcriptional activation and interaction with different cellular proteins are important for its oncogenic potential. Major objectives of the present project are to unravel the functions of the Meq using state of the art technologies of BAC mutagenesis, proteomics and analysis of gene expression profiles in Meq-expressing lymphocytes. In addition, we also propose to examine the molecular events and kinetics of viral integration during latency and transformation using Fluorescent in situ hybridisation (FISH). Lastly, using accurate quantitative PCR methods that we have developed, we will examine the virus load in various tissues of vaccinated birds to examine whether the amount of vaccine virus in the vaccinated birds is related to the protection. The project would provide a fundamental understanding not only on the molecular mechanisms of MDV oncogenicity, but also on the multitude of factors associated with neoplasia in general.
 
Description As part of this grant, we have developed infectious bacterial artificial clones of a number of herpesviruses that allow the application of deletion analysis. Using these approaches, we have identified the roles of important virus-encoded genes in the biology of viruses
Exploitation Route Role of microRNA homologs of viruses can help in identifying the biological functions of other microRNAs as we have demonstrated.
Sectors Agriculture

Food and Drink

 
Description Dissecting the molecular pathways of MDV oncoprotein Meq for understanding pathogenesis and aid vaccine development
Amount £440,000 (GBP)
Funding ID BB/R007896/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 03/2018 
End 03/2021
 
Description Innovations in control of avian infectious diseases for sustainable growth and food security in low and middle income countries
Amount £355,000 (GBP)
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 12/2016 
End 11/2021
 
Description Poultry Health course 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poultry Health Course is run as a residential and online course to transfer recent advances in avian disease research from the laboratory to the field.
Year(s) Of Engagement Activity Pre-2006
URL http://www.poultryhealthcourse.com/