Completed Infection & Immunity Genetics & Molecular Biology

Contribution of the miRNA-interferon interaction to human disease

Funder Wellcome Charity-funded
Recipient organisation University of Edinburgh
Funding £1.8M
Period Feb 2021 — Jan 2026

In plain English

AI plain-English summary

When a person catches a cold, their body unleashes a flood of antiviral proteins called interferons—but if that flood never stops, it can trigger lupus or other autoimmune diseases. This project investigates how tiny RNA molecules called microRNAs act as a brake on interferon production, and how that brake can fail. The problem is that doctors currently have no way to predict or prevent the harmful overproduction of interferons in autoimmune patients. The researcher has already shown that microRNAs and interferons regulate each other in a tight feedback loop. Now they want to map exactly how that loop breaks in two specific conditions: 22q11.2 deletion syndrome, where microRNA levels are abnormal, and systemic lupus erythematosus, where interferon levels are too high. If this fundamental science succeeds, it will reveal the molecular wiring that connects microRNA defects to immune overreaction. That knowledge could eventually point to new drug targets for autoimmune diseases—conditions that affect hundreds of thousands of people in the UK alone. This is curiosity-driven research into a basic biological mechanism, but similar work on microRNA regulation has already led to experimental therapies for hepatitis and cancer. A clearer map of the interferon–microRNA interaction could open the same path for autoimmune disease.

View original technical description
The type I interferon (IFN) response is the major antiviral pathway in mammals but needs to be tightly regulated to ensure effective defence against viruses whilst avoiding the negative consequences of their overproduction, resulting in autoimmune and autoinflammatory diseases. I have recently demonstrated a central role for microRNAs (miRNAs) in maintaining optimal IFN levels, and conversely, that IFNs are important regulators of miRNA expression. These results led me to hypothesise that there is a tight interaction between the IFN and miRNA pathways, which contributes to specific traits of human diseases where one component of this interaction is altered. Supporting this hypothesis, our unpublished results show that diseases characterised by altered miRNA expression, such as 22q11.2DS, exhibit a dysregulated IFN response. Vice versa, diseases characterised by an abnormal IFN response, such as systemic lupus erythematosus, display altered miRNA levels. I aim to identify the mechanisms by which the miRNA biogenesis and IFN pathways interact and study the role of this interaction in diseases where the IFN or miRNA biogenesis pathways are altered. These results will provide a mechanistic perspective to some of the common but unexplained traits presented in these diseases and provide novel targets for intervention strategies.

View the original record at the funder ↗

Researchers

Sara Macias (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Molecular mechanisms for type-I Interferon dysregulation
Elaboration of the type I interferonopathies
Control of type III interferon expression and Herpes simplex virus type 1 replication by miR-200
Splitting STAT Dimers to Understand Interferon Balance: A Strategy to Dissociate Beneficial and Detrimental Interferon Effects in Infection?
MicroRNA coupling of the sterol metabolic network to the antiviral immune response

Original classification

Senior Research Fellowship

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.