This project is eligible for a University of Edinburgh 3.5 year PhD studentship.
Project Description: Mareks disease (MD) is a lymphoproliferative disease of chickens with a complex pathogenesis, characterized by oncogenic transformation of T cells that infiltrate lymphoid tissues, peripheral nerves and visceral organs. MD is one of the major diseases affecting poultry health and welfare worldwide with a global annual estimated loss close to $2 billion to the poultry industry. . We have generated data on the genome-wide binding of Meq (the major MDV oncogene), methylation patterns during transformation, and differences in gene expression between active and latent viruses (manuscripts in preparation), and have carried out extensive investigations into the molecular mechanisms of Meq-induced oncogenesis.
As part of past, current and future molecular investigations into MDV infection, we have generated or will generate extensive RNA-Seq, microRNA-Seq, and IsoSeq data on infected and uninfected cell lines, both with and without knockout of key genes. Using our own and publicly available data, we will ask the following key questions:
1. What is the entire complement of RNA transcripts expressed by MDV during transformation? Using both Illumina and IsoSeq data we will reconstruct all RNA isoforms expressed by the virus under different conditions
2. What is the entire complement of RNA transcripts expressed by the host during transformation? Using both Illumina and IsoSeq data we will reconstruct all RNA isoforms expressed by the host under different conditions
3. How do these RNA isoforms change in expression over time and between conditions? How does that relate to e.g. knockout of specific transcription factors and transcription factor binding sites?
4. What is the entire complement of microRNAs expressed by either virus or host? Do these change in expession over time and between conditions? What are the predicted targets of these microRNAs and does microRNA expression (anti)correlate with target gene expression?
The outputs are likely to increase our knowledge of the molecular basis of MDV infection, enable us to prioritise variants for MDV resistance in chickens, and design new vaccines and intervention strategies for MDV control.
1. Mwangi WN, Vasoya D, Kgosana LB, Watson M, Nair V. Differentially expressed genes during spontaneous lytic switch of Marek's disease virus in lymphoblastoid cell lines determined by global gene expression profiling. J Gen Virol. 2017 Apr;98(4):779-790. doi: 10.1099/jgv.0.000744. 2. Yao Y, Charlesworth J, Nair V, Watson M. MicroRNA expression profiles in avian haemopoietic cells. Front Genet. 2013 Aug 14;4:153. doi: 10.3389/fgene.2013.00153. 3. Robert C, Watson M. The incredible complexity of RNA splicing. Genome Biol. 2016 Dec 30;17(1):265. doi: 10.1186/s13059-016-1121-y.
Eligibility: Candidates should have or expect to have a minimum of an appropriate upper 2nd class degree. To qualify for full funding students must be UK or EU citizens who have been resident in the UK for 3 years prior to commencement.
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to RDSVS.PGR.Admin@ed.ac.uk
When applying please state clearly the title of the studentship and the supervisor/s in your covering letter.
Closing Date: 21 April 2019