HREM image of mouse head during development

This project is now closed

Investigating the role of miRNAs in type-2 immune responses during allergic inflammation and helminth infection

Project supervisor: Mark Wilson (Molecular Immunology)

The regulated development of an immune response against an invading pathogen is essential for host protection. Immunity to parasitic helminth worms, which infect almost 1/3 of the world’s population, is mediated by a type-2 immune response orchestrated by T helper 2 (Th2) cells. A dysregulated type-2 response to infectious and non-infectious material, such as allergens, can cause significant immune-mediated pathology including local tissue damage, fibrosis and organ failure, observed in severe asthma and some helminth-infected cases. Understanding how Th2 cells and the downstream type-2 immune cascade is regulated will allow for more focused intervention to either inhibit type-2 immune responses (to prevent severe allergic diseases) or enhance type-2 immune responses (to enhance anti-parasite immunity).

Small (~22nucleotides) non-protein coding RNA species, such as miRNA’s, regulate protein-coding genes at the mRNA level. By binding to the 3’UTR region of mRNAs, miRNA’s inhibit translation, degrade or de-adenylate mRNA. We have identified several candidate miRNA’s that target genes involved in type-2 immune responses. We hypothesise that these miRNA’s, acting together or alone, influence the magnitude and function of type-2 immunity and the severity of allergic reactions and potency of anti-helminth immunity.

This project will involve in vitro (cell culture systems, transfection and gene manipulation assays, high throughput proteomics and embryonic stem cell technologies to generate new animal models) and in vivo disease modelling (intestinal and / or tissue helminth and allergic disease) to address the following three aims:

  1. Identify and validate the tissue- and cell-specific expression of candidate miRNA’s, mRNA and protein target levels in helminth-infected or allergic diseased tissues.
  2. Identify the function of candidate miRNA’s in the development of type-2 immune responses.
  3. Manipulate miRNA’s using genetic approaches to identify the requirement of the candidate miRNA’s and their targets in anti-helminth immunity and allergic reactions.

See also

Top of page

© MRC National Institute for Medical Research
The Ridgeway, Mill Hill, London NW7 1AA