Skip to main content

PhD project title

 

Understanding Antiviral Immunity in the Lung During Infection with Established and Emerging Viruses as Causes of Acute Respiratory Distress Syndrome (ARDS)

Outline description, including interdisciplinary, intersectoral and international dimensions 

 

The COVID-19 pandemic caused by SARS-CoV-2 has highlighted the paucity in our understanding of the molecular pathogenesis of viral infections in the lung with regards to identifying successful treatments. This challenge is compounded by the rapid international spread in an inter-connected world of previously-unknown and diverse emerging viruses that jump from animals into humans. Identification of successful interventions thus requires an interdisciplinary approach between both human and veterinary scientists and clinicians operating across academia and industry.

Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical syndrome characterized by respiratory failure with high morbidity and mortality and no specific treatment options. Diverse established and emerging viruses can cause ARDS in people, such as influenza viruses and coronaviruses. The ability of viruses to productively infect and/or cause dysfunction and inflammation in alveolar epithelium cells in the lung can precipitate ARDS. Therefore, targeting host/pathogen interactions may thus be expected to prevent and treat ARDS. However, our understanding of lung antiviral immunity in alveoli is lacking.

This proposed project aims to characterise the antiviral immune landscape of alveolar epithelial cells in vitro and in vivo during infection and inflammation with a panel of pathogenic viruses to identify core protective and pathogenic responses that could comprise targets for therapeutic intervention and/or inform vaccine development.

The successful candidate will combine cutting-edge virus and cell molecular biological approaches, involving high-containment SARS-CoV-2 work, experience in large animal in vivo experiments, and use of clinical ARDS samples from COVID-19 patients. Techniques include the generation of recombinant viruses, host gene editing, and epithelial cell biology. This project is built on an intersectoral collaboration between academic QUB ARDS and human virology researchers and veterinary molecular virologists at AFBI. It is expected that during this project the candidate will generate a robust understanding of fundamental molecular cell biology, virology and innate immunology.

The research will address the ability of common respiratory viral pathogens to infect the lower airways of patients including the coronavirus that causes Covid-19 but also other viruses including rhinovirus. These are pathogens that infect a lot of patient groups including people with Cystic Fibrosis and Chronic Obstructive Pulmonary Disease (COPD). The implications for the research are wide-reaching as COPD in particular affects more than 250 million people worldwide. As such, the research findings will be published in high impact journals such as the American Journal of Respiratory and Critical Care Medicine  and presented at International meetings such as the American Thoracic Society and European Respiratory Society meetings which are attended by more than 20,000 people each every year.

Key words/descriptors

Viruses, SARS-CoV-2, Lung, ARDS

Fit to CITI-GENS theme(s)

This project fits into the Life Sciences CITI-GENS theme.  

Supervisor Information

 

 

First Supervisor: Prof. Cliff Taggart   School: Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine Dentistry and Biomedical Sciences

Second Supervisor: Prof. Danny McAuley    School: Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine Dentistry and Biomedical Sciences

Third Supervisor: Dr Ken Lemon              Company:  Virology Branch/Veterinary Division, Agri-Food and Biosciences Institute (AFBI), Stormont, Belfast, NI, UK.

Name of non-HEI partner(s)

Agri-Food and Biosciences Institute (AFBI)

Contribution of non-HEI partner(s) to the project:

 

 

The successful candidate will carry out placement(s) at the collaborating non-HEI partner, AFBI (Belfast), with molecular virologist and Principal Scientific Officer Dr Ken Lemon.

AFBI already has a number of existing collaborations with QUB. AFBI is a large multi-disciplinary organisation involved in high technology research and development, diagnostic and analytical testing for DAERA and other Government departments, public bodies and commercial companies in NI, and worldwide. With relevance to this project, AFBI has a focus on “Animal, plant and human health and welfare”. AFBI's ‘non-departmental public body’ status enables it to be innovative and entrepreneurial in its approach to business development. AFBI is forging new partnerships with other scientific institutes and research organisations and extending the range of services it offers. This enables AFBI’s unique breadth of scientific capabilities in the areas of agriculture, animal health, food, environment and biosciences to be offered to a wider prospective national and international customer base.

Dr Lemon has over two decades of experience in molecular virology and viral pathogenesis of human and animal viruses having worked in academia at QUB and in industry at AstraZeneca/MedImmune helping develop the ‘flu-mist’ influenza vaccine for children. While now at AFBI, Dr Lemon is currently working on a number of projects to understand the molecular pathogenesis of lung viral infections in large animals, including influenza A in pigs, influenza D in cows and bovine respiratory syncytial virus or coronavirus infection in cows. AFBI/Dr Lemon’s major interest is in the successful generation of safe and efficacious vaccines for animals. Specifically, the candidate will 1) avail of AFBI’s experience in molecular virology, and 2) exploit access to large animal infection models of lung viral infections and disease. Dr Lemon’s experience in molecular virology and viral pathogenesis will be integral to the success of this project. It is foreseen that this collaboration will aid both QUB (human virology/clinical side) but also AFBI in the development and marketing of safer vaccines to protect against severe lung disease in pigs and cows. Furthermore, this project will aid the development of closer links between human and animal virologists and clinicians at QUB and AFBI.

 

 

Research centre / School

 Wellcome-Wolfson Institute for Experimental Medicine (WWIEM)

Subject area

Virology, Innate immunology, Inflammation