Website The University of Birmingham
Details
The study of human adenoviruses has been fundamental towards our understanding of many of the molecular pathways that underlie cellular processes such as cell growth and cell death. An understanding of adenovirus-host cell biology has also led to the development of gene therapy and vaccination vectors, whilst conditionally-replicating adenoviruses have been developed as cancer therapeutic agents. Studies of adenovirus infection outbreaks have indicated that infections can present at a high frequency as acute respiratory distress syndrome resulting in high patient mortality; immunocompromised individuals, neonates and infants are the most susceptible to life-threatening adenovirus infections. Despite our knowledge, there is not an effective antiviral therapy publically-available for the treatment of severe adenovirus infections.
Our laboratory studies how adenovirus interacts with host cell signalling pathways to promote viral replication. In this regard, we are particularly interested in how adenovirus engages with the ubiquitin-proteasome system and ubiquitin-like proteins to regulate host cell DNA damage response pathways. The current project aims to expand on studies currently ongoing in the laboratory to identify proviral and antiviral cellular factors that can be targeted therapeutically to limit viral replication. We will use proteomic techniques such as mass spectrometry to identify novel proviral/antiviral cellular factors, and genomic techniques such as CRISPR, allied with super-resolution microscopy, to establish the molecular basis of proviral/antiviral activities and determine whether these factors can be targeted to limit viral replication.
Applicants should have a strong background in virology and molecular and cellular biology. Previous laboratory experience is essential. Applicants should be ambitious, enthusiastic and self-motivated, and hold at least an Upper Second Class Honours Degree, or equivalent, in a relevant biological subject.
Funding Notes
This PhD position is only open to self-funded PhD students or those that have secured a funded scholarship
You can search for relevant funding opportunities here: https://www.birmingham.ac.uk/study/international/fees/scholarships and https://www.birmingham.ac.uk/funding/postgraduate.
References
Nazeer R, Qashqari FSI, Albalawi AS, Piberger AL, Tilotta MT, Read ML, Hu S, Davis S, McCabe CJ, Petermann E, Turnell AS. Adenovirus E1B 55-Kilodalton Protein Targets SMARCAL1 for Degradation during Infection and Modulates Cellular DNA Replication. J Virol. 2019 Jun 14;93(13):e00402-19. doi: 10.1128/JVI.00402-19. PMID: 30996091; PMCID: PMC6580949.
Donovan-Banfield I, Turnell AS, Hiscox JA, Leppard KN, Matthews DA. Deep splicing plasticity of the human adenovirus type 5 transcriptome drives virus evolution. Commun Biol. 2020 Mar 13;3(1):124. doi: 10.1038/s42003-020-0849-9. PMID: 32170151; PMCID: PMC7070027.
Fu YR, Turnell AS, Davis S, Heesom KJ, Evans VC, Matthews DA. Comparison of protein expression during wild-type, and E1B-55k-deletion, adenovirus infection using quantitative time-course proteomics. J Gen Virol. 2017 Jun;98(6):1377-1388. doi: 10.1099/jgv.0.000781. Epub 2017 Jun 20. PMID: 28631589; PMCID: PMC5656791.
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