How does aberrant innate immune activation damage the microvasculature of the brain? (360G-Wellcome-215621_Z_19_Z)
Systemic lupus erythematosus and Aicardi-Goutières syndrome are chronic autoimmune disorders which can affect the brain of adults and children. Despite their high disease burden, there is no effective treatment for the neurological manifestations of these conditions, highlighting the need to identify defined immune pathways which drive brain damage. These diseases are characterised by aberrant activation of the type I interferon response and we have shown this pathway can damage small blood vessels of the brain. However the cellular and molecular mechanisms by which this occurs are unknown. In this proposal we will develop mouse models of interferon dysregulation, linked to human experimental medicine studies of "interferonopathic" diseases such as neurolupus. Our overarching aim is to understand the role of this pathophysiological axis in mediating brain disease in disorders such as lupus, with a view to developing therapeutic interventions. Goal 1. To determine the cellular and molecular targets of type I interferon within the brain’s microvasculature. Goal 2. To identify the influence of type I interferon subtype on microvascular disease Goal 3. To understand how microvascular disease arises in a lupus model of spontaneous interferon activation
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Grant Details
| Region | Scotland |
| Award Date | 2019-04-02T00:00:00+00:00 |
| Sponsor(s) | Prof Giles Hardingham |
| Internal ID | 215621/Z/19/Z |
| Planned Dates: End Date | 2026-08-31T00:00:00+00:00 |
| Planned Dates: Start Date | 2019-09-01T00:00:00+00:00 |
| Amount Awarded | 1613892 |
| Financial Year | 2018/19 |
| Lead Applicant | Dr David Hunt |
| Grant Programme: Title | Senior Research Fellowship |
| Applicant Surname | Hunt |
| Approval Committee | Science Interview Panel |
| Recipient Org: Country | United Kingdom |
| Recipient Org: City | Edinburgh |
| Has the grant transferred? | No |
| Research conducted at multiple locations? | No |
| Total amount including partnership funding | 1613892 |