Regulation of anti-parasite macrophage function by non-coding RNA

This project will assess the role of long non-coding RNA in the function of macrophages that are important in anti-helminth immunity.

Parasitic helminths continue to infect more than 2 billion people worldwide and cause a range of diseases. Host protection against these parasites depends on strong type-2 immune responses, which directs macrophages towards an “alternative-activation” phenotype. These cells carry out multiple roles within the host, including parasite killing and repair of tissue damage.

Whilst the function of proteins that are characteristic of type-2 macrophages is now becoming clearer, the role of non-coding RNA in controlling cell function is much less well understood. In this regard, large-scale RNA sequencing projects revealed two surprising findings: the majority of the mammalian genome is transcribed, but the bulk of this is not translated into protein. So-called small non-coding RNAs (200nt) non-coding (lnc) RNA. Unlike miRNA, lncRNA do not appear to have a conserved mechanism of function, and can be active in the cytosol or nucleus, at unique or multiple chromosomal locations. A number of recent studies have characterised lncRNA function in macrophages that are activated by microbial stimuli (“classically activation”) and identified several molecules that coordinate the anti-microbial response. However, the role of lncRNA in type-2 macrophages is unknown.

This project will focus on understanding the role of lncRNA in type-2 macrophage function. This will involve the student using a variety of cellular and molecular techniques (e.g. analysis of our own RNAseq data, gene-editing, in situ hybridisation, RNA-IP), in vitro cell culture and in vivo infection studies. This collaborative project will provide training in host immunity and host-pathogen interactions, and be supervised by experts in helminth immunity and the control of cellular function by non-coding RNA. The project will be carried out in the Centre for Immunology and Infection, Department of Biology at the University of York. The student will benefit from a strong research environment with multiple groups studying the cellular and molecular basis of infectious and non-infectious diseases, as well as access to cutting-edge experimental platforms in the Bioscience Technology Facility. This project will be suitable for a graduate in biology, biomedical sciences, or related subjects, with a strong interest in the control of gene expression, immunology or infection biology.