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

Supervisor:   Dr James Hewitson

Co-Supervisor:  Dr Dimitris Lagos

Project description:

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) include well-characterized microRNAs (miRNA) that regulate mRNA translation, but much less is known about the function of the long (>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.

We strongly encourage you to email the project supervisor prior to submitting an application to discuss your suitability for this project.  Please email:  james.hewitson@york.ac.uk

Funding:  This studentship is fully funded for 3 years by the Department of Biology and covers: (i) a tax-free stipend at the standard Research Council rate (£14,533 for 2017-2018, to be confirmed for 2018-2019), (ii) research costs, and (iii) tuition fees at the UK/EU rate.

Start date: October 2018

Please read the 'How to apply' tab before submitting your application.

Applications are now closed

Interviews will be held on Monday 5 or Tuesday 6 February 2018 - TBC