The interaction of classical swine fever virus (CSFV) with porcine cells
Classical swine fever virus (CSFV) is a highly contagious virus that is exotic virus to the UK and an outbreak of CSF would have severe socioeconomic and animal welfare impacts. While there is a very potent vaccine available, its use is limited by the inability to differentiate vaccinated from infected animals. To gain insights into the mechanisms of vaccine protection to inform on the generation of better vaccines this project will involve the characterisation of the porcine host response to the existing potent vaccine and comparison to immune responses induced upon infection with pathogenic CSFV strains to identify the mechanisms of protection verses infection.
Start date1 October 2022
This studentship covers the University of Surrey registration fee, doctoral stipend matching UK Research Council National Minimum and bench fees. Due to funding constraints only UK applications can be considered. This is a full time PhD project, which is planned for a period of three years.
Classical swine fever virus (CSFV) is a highly contagious often fatal virus that infect pigs and other suidae. Clinical signs of disease include fever, loss of appetite and haemorrhages. CSFV is exotic to the UK but an outbreak would have severe consequences to the swine industry with socioeconomic and animal welfare impacts. While there is a very potent vaccine available, its use is limited due to the inability to differentiate infected from vaccinated animals (DIVA). Gaining a better insight into the immune mechanisms which afford vaccine protection would inform the generation of better vaccines with DIVA properties. This project therefore aims to better understand and characterise the porcine host response to the existing potent vaccine and to directly compare these responses to those induced upon infection with a pathogenic CSFV strain. This would serve to identify the immune mechanisms which provide protection verses the mechanisms modulated by viral infection.
While the project will make use of established in vivo animal models it will also aim to develop and employ in vitro techniques to study virus and vaccine interactions with single tonsillar cell populations in addition to mixed populations of tonsillar cells in vitro including developing methods for organoid cultures. To achieve these aims, the student will employ methods beyond cell culture, such as microscopy (including confocal), multi-parameter flow cytometry (including cell sorting), and transcriptomic technology.
This project builds on an existing long running programme of research in this area, where the team has already concluded several successful projects and successfully supervised a number of previous and ongoing PhD students.
The project will be carried out in collaboration with the APHA and the successful candidate will be mainly working at their Weybridge labs. This project will require working in containment, where health and security clearances will be required before starting the PhD.
Graham SP, Everett HE, Haines FJ, Johns HL, Sosan OA, Salguero FJ, Clifford DJ, Steinbach F, Drew TW, Crooke HR (2012) Challenge of pigs with classical swine fever viruses after C-strain vaccination reveals remarkably rapid protection and insights into early immunity PLoS One.;7:e29310. DOI: 10.1371/journal.pone.0029310
Edwards, J.C., Everett, H.E., Pedrera, M., Mokhtar, H., Marchi, E., Soldevila, F., Kaveh, D.A., Hogarth, P.J., Johns, H.L., Nunez-Garcia, J., Steinbach, F., Crooke, H.R., Graham, S.P., 2017. CD1- and CD1+ porcine blood dendritic cells are enriched for the orthologues of the two major mammalian conventional subsets. Nat Sci Rep 7, 40942. DOI: 10.1038/srep40942
Soldevila F, Edwards JC, Graham SP, Stevens LM, Crudgington B, Crooke HR, Werling D & Steinbach F (2018) Characterization of the Myeloid Cell Populations Resident in the Porcine Palatine Tonsil. Front. Immunol. 9:1800 DOI: 10.3389/fimmu.2018.01800
McCarthy RR, Everett HE, Graham SP, Steinbach F, Crooke HR (2019) Head Start Immunity: Characterizing the Early Protection of C Strain Vaccine Against Subsequent Classical Swine Fever Virus Infection. Front Immunol. 2019 Jul 23;10:1584. DOI: 10.3389/fimmu.2019.01584.
The project will be under the supervision of Prof. Falko Steinbach (University of Surrey) and Dr. Helen Crooke (Animal and Plant Health Agency-Weybridge).
Applicants should hold a BSc (Hons) degree in a relevant biological subject. A master's degree (or equivalent training) in Virology/Microbiology or Immunology is desirable.
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If English is not your first language, please check our Veterinary, Medicine and Science programme page for language and other requirements before application.
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