Most of us are infected with several human herpesviruses, including the human cytomegalovirus (HCMV). Herpesviruses persist throughout the life of the host, in part by establishing 'latent' infections. An important site of HCMV latency is in hematopoietic progenitor cells (HPCs) and their monocyte derivatives in the peripheral blood1. HCMV is rarely symptomatic in most healthy individuals. However, viral reactivation from latency may result in congenital (present at birth) HCMV infection, which is a leading cause of birth defects linked to permanent damage in one of five infected babies (1,000 babies annually in the UK). As a result, HCMV places a significant burden on families, costing the NHS and social/educational services £330 million and the wider UK economy £420 million per year. In addition, many thousands of immunosuppressed patients, including transplant recipients, suffer life-threatening multi-organ disease due to HCMV reactivation each year1. There is neither a preventive vaccine for HCMV nor a safe and effective drug for congenital infection. Antiviral therapy in transplant patients is limited to a few drugs with significant problems such as toxic side effects, carcinogenic and teratogenic potential, and viral resistance2.
Herpesviruses have large double-stranded DNA genomes that are transcribed, replicated and packaged into capsids in the nuclei of infected cells. Nuclear DNA typically exists as chromatin composed of repeating subunits called nucleosomes. Each nucleosome consists of just under two turns of DNA wrapped around an octamer of core histone proteins. Nucleosome occupancy and composition control all DNA-driven processes in the nucleus, including transcription, replication, recombination and repair. Herpesvirus DNA is packaged into viral particles without histones. However, HCMV genomes associate with host-derived core histones in the nuclei of productively or latently infected cells, where viral DNA is thought to exist as extrachromosomal episomes3-5. It is unknown whether HCMV episomes form a nucleosomal structure during latency, how HCMV chromatin is established or how the global organisation of viral chromatin may change during successive steps of latency and reactivation.
The proposed project will investigate the global organisation and dynamics of HCMV chromatin during latency and reactivation in primary human monocytes and CD34+ HPCs. We will determine whether HCMV episomes form canonical or non-canonical nucleosome structures, how the accessibility of viral chromatin may change, and which proteins constitute viral chromatin during latency establishment, latency maintenance and reactivation from latency (Aim 1). In addition, we will identify the chromatin assembly pathways required for de novo formation of latent HCMV chromatin (Aim 2). Results from Aims 1 and 2, together with a recently completed screen for epigenetic regulators of latent viral gene expression, will guide us to critical cellular factors that control latent HCMV chromatin. Selected cellular factors will be investigated using appropriate mechanistic approaches (Aim 3). Similarly, the mechanisms by which histone-associated viral factors may control latent HCMV chromatin will be investigated (Aim 4). The results of this work will be linked to a large body of existing transcriptomic and proteomic data from latently infected monocytes and CD34+ HPCs1.
Knowledge of HCMV latent chromatin organisation and dynamics is fundamental to understanding infection outcome and pathogenesis, including transcriptional silencing during latency establishment, maintenance of latent viral genomes and reactivation of viral gene expression. This study will identify new potential therapeutic targets and provide opportunities for novel antiviral and diagnostic approaches aimed at reducing the substantial burden associated with HCMV infection and disease.
HOW TO APPLY
Please complete an application on our online portal: How to apply - Study at St Andrews - University of St Andrews
Your online application must include the following documents:
- Academic Qualifications
- CV
- English Language Qualification (if applicable)
- 2 References
FOR CSC APPLICANTS:
- Apply for your chosen course beginning in the 2026-2027 academic year by completing the research application form, by Tuesday 6 January 2026. Select the drop-down option 'I have applied for or I will be receiving a bursary or scholarship' in the Fees and Funding section of the application form and specify 'CSC St Andrews Scholarship'. After applying, you must then allow at least three working days for processing and issue of your log in details before the next step.
- Apply for scholarships and funding by logging into My Application where you can search and apply for the CSC/St Andrews Scholarship.
- Click View the scholarships and funding catalogue to apply.
- Select 2026/7 as the Academic Year and click Refresh list.
- Locate China Scholarship Council - University of St Andrews Scholarships (PhD) in the list of scholarships (using the filter box if necessary), click Apply and complete the short application form.
- Application deadline: 23:59 (GMT) on Friday 9 January 2026.
- You may also use the catalogue to search and apply for other scholarships for which you are eligible.
More details can be found here: China Scholarship Council - Study at St Andrews - University of St Andrews
CONTACT
Queries on the project can be directed to the project supervisor.
Queries on the application process can be directed to Rachel Horn at pgrecbiology@st-andrews.ac.uk
