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      Research Statement

       

      Human respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants worldwide and also causes considerable morbidity and mortality in the elderly and immunecompromised individuals. Re-infections are common throughout life. Despite more than 50 years of research there are no vaccines or specific therapeutics against RSV. Importantly, the mechanisms by which RSV causes disease in humans remain poorly understood. 

      The Power group has developed models of RSV infection based on well-differentiated primary paediatric airway epithelial cell cultures (WD-PAEC), the primary targets of RSV infection in vivo. These cultures are derived from both bronchial and nasal brushes of airway epithelium in ethically approved protocols. Our RSV/WD-PAEC model derived from bronchial epithelium demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs, both at the cellular and molecular levels. This research indicated that our model provides an authentic surrogate for RSV infection of lower airway epithelium in vivo. Similarly, our RSV/WD-PAEC model derived from nasal epithelium provided the means to comprehensively study RSV infection in authentic paediatric upper respiratory tract epithelium tissue. Our exploitation of these models has provided several novel insights into the consequences of RSV infection of paediatric airway epithelial cells that are the basis of ongoing research. In particular, using nasal-derived WD-PAECs from cohorts of infants with defined histories of severe and mild RSV disease, respectively, we have generated data identifying potential gene biomarkers of severe RSV disease in infants and are currently validating them. 

      We are confident that these models will provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines and/or therapeutics. Be extension, we expect that they will also provide the basis for authentic pre-clinical models to test novel anti-RSV therapeutics. 

      Although our models are based on RSV infections, these cultures will be undoubtedly adaptable to studying the molecular pathogenesis of other important respiratory viruses, such as influenza virus and human parainfluenza viruses. Indeed, by way of comparison with RSV, we have extensively characterised the consequences of WD-PAEC infection with Sendai virus, a murine parainfluenza virus type 1 (mPIV1) that is considered non-pathogenic in humans. Sendai virus is of interest to us and others as a live attenuated viral vaccine vector for RSV antigens. As such, studying its interaction with WD-PAECs provided novel insights into the cytopathogenesis of Sendai virus in paediatric airway epithelial cells. 

      This research programme is the result of highly productive collaboration with Prof. Mike Shields and members of the Respiratory Research Cluster at QUB. It has attracted substantial peer-reviewed research funding from local and national funding agencies, as well as substantial research investment from international pharmaceutical and biotechnology companies.

       

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        ISSNs: 0264-410X

        Additional searchable ISSN (Electronic): 0264-410X

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        ISSNs: 1932-6203

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      Contribution to conference papers, events and activities

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