Postdoc Research Assistant/Associate in Interferon-mediated Neuropathology

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The Role
Type I interferons (IFN-I) are best known as an essential mediator of antiviral immunity, yet their neurotoxic potential is increasingly acknowledged. A common signature of dysregulated IFN-I signalling has been identified across a diverse range of neurological disease states, including Alzheimer's and Parkinson's diseases as well as aging and vascular diseases of the CNS.

Identification of shared pathomechanism in these disorders would offer an efficient route to therapy. Dementias alone cost the UK economy more than £17 billion according to UK government estimates. The burden of disease is expected to rise as populations age, with projections suggesting 25% of the European population will be aged over 65 in 2030. Yet fundamental questions remain unanswered concerning the possible involvement of IFN-I in neurological disease, foremost among them whether IFN-I contributes directly to CNS disease or is induced as a consequence of neurological damage.

Arguably the strongest evidence for a directly causal role in neuropathology comes from a group of rare inborn errors of immunity termed type I interferonopathies [PMID: 34671122]. Our group previously identified a type I interferonopathy associated with homozygous mutation of STAT2 [PMID: 31836668]. We have generated a mouse model of this disorder, in which neurological disease is recapitulated and where multiple CNS cell types including microglia, neurones and endothelial cells exhibit pathological effects (unpublished). This project explores the cellular drivers of IFN-mediated pathology using conditional in vivo expression of the pathogenic allele in individual cell types, allied with human induced pluripotent stem cell (hiPSC) models of the corresponding cell types in vitro. We will also assess novel IFN-I inhibitors developed in partnership with medicinal chemistry collaborators. This project will shed light on direct and indirect pathogenic properties of IFN-I in the CNS, providing a framework for interpreting pathomechanism in neurological disease.

This post is funded by the UK Medical Research Council and is fixed-term until 10th July 2027.

For informal enquiries contact:
Dr Christopher Duncan: christopher.duncan@ncl.ac.uk
Prof Sophie Hambleton: sophie.hambleton@ncl.ac.uk

Find out more about the Faculty of Medical Sciences here: https://www.ncl.ac.uk/medical-sciences/.

Find out more about our Research Institutes here: https://www.ncl.ac.uk/medical-sciences/research/institutes/.

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