Phd Studentship in The Infection, Immunology and

2 weeks ago

London, United Kingdom University College London Full time

**Ref Number**

B02-06434

**Professional Expertise**

Research and Research Support

**Department**

School of Life & Medical Sciences (B02)

**Location**

London

**Working Pattern**

Full time

**Salary**

See advert text

**Contract Type**

Fixed-term

**Working Type**

On site (> 80% of working time)

**Available For Secondment**

No

**Closing Date**

22-Feb-2024

**About us**:
A 3-year PhD Studentship in the Infection, Immunity and Inflammation Department, funded by the Rosetrees Trust, is available within the UCL GOS Institute of Child Health. The studentship will commence from April/May 2024, under the supervision of Professor Judy Breuer and Dr Cristina Tommasi.

**Project title**:
Identification Of Druggable Targets In Pathways Common To Skin-replicating Viruses To Enable Future Development Of Broad-spectrum Antivirals

**Hypothesis/Aims**:
Our group is interested in viruses that are able to replicate in skin, including monkeypox (mpox), which has recently emerged as a major public health threat, herpes simplex virus (HSV) and varicella-zoster virus (VZV), which can cause severe disseminated infections, and human papillomavirus, the cause of cervical cancer. In all cases replication in skin is critical to viral transmission and pathogenesis and the development of drugs and vaccines that interrupt viral replication in skin would have major benefits for their control.

Preliminary data suggest that, although from different viral families, these viruses replicate using the same proteins and signalling pathways, including some that are unique to skin and indeed, this may be what confers epithelial tissue tropism. This project proposes to characterise in detail how herpes simplex and poxvirus (vaccinia and monkeypox) utilise common pathways to replicate in skin, identifying potential targets for the development of broad-spectrum antiviral therapies.

To this aim, we will:

- Characterise the transcriptome and proteome of HSV-1 and vaccinia virus (VACV) in epithelial differentiation models.
- Characterise epidermal pathways that are critical for HSV-1 and VACV epidermal replication.
- Identify inhibitors of the identified pathways and therefore of HSV-1, VACV and mpox epidermal replication.

**6-12 Month Plan (e.g., experimental approaches, data collection, preliminary analyses)**:

- training on different skin models
- training on HSV-1 and VACV viruses culture
- proteomics analyses of HSV-1 and VACV skin infections

**Timeline**

Year 1: training in experimental models and proteomics analysis of HSV-1 and VACV skin infections.

Year2: characterisation of pathways in HSV-1 and VACV skin infections

Year3: testing of inhibitor drugs on HSV-1 and VACV skin infections and ultimately testing of selected inhibitors on mpox infections.

**Research and Policy outputs**:
Key output of this project will be a better understanding of how different skin viruses replicate in skin and identification of inhibitors that could pave the way for future development of broad-spectrum antivirals.

**References**:

- Jones M, Dry IR, Frampton D, Singh M, Kanda RK, Yee MB, et al. RNA-seq Analysis of Host and Viral Gene Expression Highlights Interaction between Varicella Zoster Virus and Keratinocyte Differentiation. PLOS Pathogens 2014;10:e1003896.
- Tommasi C, Breuer J. The Biology of Varicella-Zoster Virus Replication in the Skin. Viruses 2022;14:982.
- Tommasi C, Rogerson C, Depledge DP, Jones M, Naeem AS, Venturini C, et al. Kallikrein-Mediated Cytokeratin 10 Degradation Is Required for Varicella Zoster Virus Propagation in Skin. J Invest Dermatol 2020;140:774-784.e11.

**About the role**:
**Environment**:
The student will work within the UCL Great Ormond Street Institute of Child Health (UCL GOS ICH), with the Breuer research group and will join an international and highly collaborative environment. Within Professor Breuer’s group Dr Tommasi is working on VZV skin infection, two post-doctoral researchers are working on SARS-CoV-2 and other respiratory viruses and a post-doctoral researcher working on developing novel metagenomic methods. In addition there are a further 4 computational post-doctoral researchers working on the evolutionary genomics of SARS-CoV-2, CMV, EBV and norovirus, a Henry Wellcome Fellow working on development of new metagenomic computational methods and one PhD student working on pathogen metagenomics. In addition, there are two wet lab post-doctoral researchers working on development of metagenomics and the pathogenesis of CMV and EBV.

The student will learn about key aspects of HSV-1, VACV and monkeypox skin replication.

This Studentship presents a unique opportunity to conduct supervised research at and be a part of the research community, being an integral part of the exciting and thriving research team.

**About you**:
Applicants should have, or expect to receive an upper second-class Bachelor’s degree, with a Master’s degree (or equivalent work experience) in a relevant discipline or

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