BBSRC EASTBIO DTP CASE: Synthetic-interferon mimetics as potential cross-species therapeutics

The interferons (IFNs) are a family of cytokines that protect against disease and viral infection and which can be exploited in immunotherapy strategies to treat a range of diseases across mammalian species. The consequences of introducing therapeutic IFN to patients are both a direct effect on the target cells and a more indirect response through activation of the immune system (Parker et al. 2016; Zitvogel et al., 2015). A major barrier to widespread use of naturally occurring IFN-molecules in both humans and companion animals, such as dogs, is their pleiotropic nature and severe side-effects when delivered at appropriate doses.

The University of Edinburgh is working with Alfacyte whose mission is to develop innovative synthetic alpha-interferons with an improved side-effect profile as biologics to treat a variety of conditions. In Edinburgh, we aim to generate and characterise the mechanism of action of IFN-mimetics generated form bespoke synthetic combinatorial libraries that can be used to screen for biologics with desirable characteristics, such as stability and bioavailability. We are also seeking synthetic IFN derivatives which favour activation of one branch of the immune response over another. Using information gained from screening in combination with computational biology we aim to optimise potential IFN-pathway targeted biologics as new across-species agents.

To understand the mechanism of action of IFN-mimetics the effect of potential biologics on cellular signalling and proteostasis will be investigated using a systems proteomic approach. This will involve a systematic analysis on the localisation, interactions, modification and function of key downstream IFN-activated signalling pathways/protein in appropriate primary cell, stem cell and immune cell models. This approach is designed to identify ‘omics’-based biomarkers as a readout of the response to synthetic-IFN and determine the potential utility of next generation IFN-mimetics in the treatment of diseases such as cancer which would benefit from the One Health approach of comparative medicine to treat both humans and companion animals.

The student will work as part of team focused on using synthetic- and computational-biology to identify candidate biologics in the first part of their PhD. They will then carry-out systems proteomics and bioinformatics analysis in selected cell models in the second half of their studies before validating candidate biomarkers. In addition, the student will have access to expertise and training with Alfacyte. The student will therefore receive interdisciplinary training in biochemistry, synthetic biology and in silico protein modelling as well as systems based proteomic analysis linked to bioinformatics and industry standard immunological assay development.

Application procedures:
Completed application forms along with your curriculum vitae should be sent to our PGR student team at [Email Address Removed]

Reference Request Form – please fill in your name and send the form to two academic referees. Your referees should send the completed forms to our PGR student team at [Email Address Removed]

Downloads:
Application form - http://www.roslin.ed.ac.uk/postgraduate/eastbio/eastbio-application-form-2017.doc

Reference request form - http://www.roslin.ed.ac.uk/postgraduate/eastbio/eastbio-reference-request-form-2017.doc