Lasting Impressions: How Viral Infections Shape Epigenetic Memory and Innate Immunity

The University of St Andrews is pleased to offer a scholarship funded by St Leonard’s Postgraduate College, to support an exceptional student undertaking doctoral research in the following project:

Lasting Impressions: How Viral Infections Shape Epigenetic Memory and Innate Immunity

Project Description:

The innate immune response serves as our first line of defence against invading pathogens days before the cells and antibodies of the adaptive immune system can take effect. The transcription of innate immune genes depends on epigenetic marks that decorate our DNA and the DNA-associated proteins referred to as histones. Many viruses cause changes to these epigenetic marks, some of which are stably transmitted through cell divisions forming the basis of cellular memory. Mounting evidence for innate immune memory has emerged, suggesting that infections can ‘train’ innate responses via epigenetic mechanisms to confer resistance to secondary pathogen encounters. In addition to this beneficial role, epigenetic changes conferred by viruses may contribute to chronic conditions including cancer (‘hit-and-run’ oncogenesis).

The proposed project will investigate for the first time whether human pathogenic viruses leave common or distinct signatures in the host epigenome and transcriptome, and whether these ‘impressions’ contribute to epigenetic memory and trained innate immunity after the initial infection has cleared. The resulting molecular signatures will inform novel diagnostic and therapeutic approaches, and they may help explain sustained disease triggered by acute viral infection.

The project will focus on four distinct human viruses: Adenovirus (AdV), Cytomegalovirus (CMV), Influenza A Virus (FluA) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). AdV are small DNA viruses that cause a range of illnesses and have been used as a cancer model. CMV, a large DNA virus of the herpesvirus family, is a leading cause of birth defects and disease in transplant patients. FluA is a small RNA (negative sense) virus causing seasonal epidemics with high morbidity and mortality. SARS-CoV-2, a large RNA (positive sense) virus, is the cause of the ongoing COVID-19 pandemic with currently 60 million confirmed cases worldwide resulting in more than 1.4 million deaths.

The project has three main aims:

·        Define epigenetic signatures: do different viruses leave common or distinct ‘impressions’?

·        Examine epigenetic memory: do infection-related changes persist after the virus has left?

·        Explore trained immunity: do infection-related changes boost the innate immune system for secondary pathogen encounters?

The scholarship will support a co-tutelle doctoral degree programme between the School of Biology at St Andrews and the Heinrich Pette Institute – Leibniz Institute for Experimental Virology (HPI) at the University of Hamburg in Germany. The student will be supervised by Dr Michael Nevels (University of St Andrews) and Professor Thomas Dobner (HPI/University of Hamburg).

Additional Criteria:

Applicants must not already (i) hold a doctoral degree; or (ii) be matriculated for a doctoral degree at the University of St Andrews or another institution.

Duration of award:

Up to 3.5 years. The student will be expected to spend approximately half of the award term at the University of St Andrews and half at the HPI/University of Hamburg. The successful candidate will be expected to have completed the doctorate degree by the end of the award term. The award term excludes the continuation period and any extension periods.

How to apply:

Apply for admission as a doctoral student – please see the advice on applying for research degree programmes.

Please indicate in your application that you wish to be considered for this Global St Andrews scholarship (reference Nevels).

Informal enquiries regarding this scholarship may be addressed to Dr Michael Nevels – email [Email Address Removed], or Prof Thomas Dobner – email [Email Address Removed].

Please contact us should you have any questions regarding the scholarship: [Email Address Removed]