PhD project

Investigation of salivary peptides as SARS-CoV-2 entry inhibitors

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Application deadline

31 October 2022

The global pandemic caused by the emergence of a novel Coronavirus in Wuhan during 2019 has had a huge impact on all aspects of human health. Among the many features that make the virus SARS-CoV-2 difficult to control are the periods of viral shedding that either precede symptoms or occur in individuals that remain asymptomatic. Therefore the oral cavity is not only an important site of viral entry but also acts as s significant source of infective material. Consequently key steps in addressing COVID-19 include understanding the sensitivity of different oral tissues to infection, assessing the importance of salivary components in priming the virus for entry, and determining if the anti-viral properties previously assigned to molecules naturally present in the mouth impact on adhesion and cell entry. It is the aim of this PhD project to develop a method to monitor the binding of viral Spike protein to oral cell lines and use this to screen for fusion inhibitors that could be utilised in therapeutic interventions that include the adaptation of oral mouthwashes to include components that can limit viral entry and onward transmission of primed virions. 

We currently have access to recombinant SARS-CoV-2 Spike protein, three oral cells lines and reagents that have allowed us to establish the expression of theproteins including ACE2, Furin and TMPRSS2. In addition, we know that under experimental conditions that upon exposure to Spike these cell lines form Syncytia, multi-nucleate cells formed by membrane fusion. Preliminary work shows that there formation can be delayed by the addition of a inhibitory peptide already described in the literature. The PhD will involve training in molecular and biochemical techniques that will enable the student to refine the experimental conditions for profiling cellular responses. The second year will exploit the techniques and conditions established to screen a number of naturally occurring anti-viral peptides found in saliva and is intended to produce insights into how important these molecules could be in protecting people from infection and also limiting the ability of an individual’s saliva to transmit infective material. It is projected that in the final year of study the most promising material and platforms will form the basis for establishing collaborations within Dundee, SLS Drug Discovery Unit, and internationally, i.e. NMI, Tuebingen, Germany.

Studies will be performed in the Molecular Biology Facility of Dundee Dental School, and students will obtain a range of skills associated with cell biology, protein analysis, transcriptional profiling and bioinformatics. The project requires a detailed understanding of Oral Science, and collaboration with DDS clinical colleagues who have expertise in Saliva, Taste bud biology, and Biomarkers will provide the applicant with a unique skill set. The supervisors have previously been successful in obtaining seed funding for this research area and are registered with the MRC/Wellcome protein portal that enables access to key COVID-19 reagents. Initial studies have been promising and the project has a high likelihood of generating significant insights into our understanding the role of the oral cavity in COVID-19 infections. 

How to apply

Deadline

31 October 2022

  1. Email Dr David Edwards to
    • Send a copy of your CV
    • Discuss your potential application and any practicalities (e.g. suitable start date).
  2.  After discussion with Dr Edwards, formal applications can be made via our direct application system. 
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Supervisors

Principal supervisor