BBSRC SWBio DTP PhD studentship: A role for lncRNAs in the transcriptional co-ordination of neighbouring genes

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP) which is a BBSRC-funded PhD training programme in the biosciences, delivered by a consortium comprising the Universities of Bath, Bristol, Cardiff and Exeter, along with the Rothamsted Research Institute. The partnership has a strong track record in advancing knowledge through high quality research and teaching, in collaboration with industry and government.

Studentships are available for entry in September/October 2019.

All SWBio DTP projects will be supervised by an interdisciplinary team of academic staff and follow a structured 4-year PhD model, combining traditional project-focussed studies with a taught first year which includes directed rotation projects.

SUPERVISORY TEAM:

Lead supervisor - Dr Hans-Wilhelm Nuetzmann, Department of Biology & Biochemistry (University of Bath)
Co-supervisors - Prof Laurence Hurst (University of Bath), Dr Keith Vance (University of Bath)
Collaborator - Dr Selene Lizbeth Fernández Valverde (LANGEBIO, National Laboratory of Genomics for Biodiversity, Irapuato, Mexico)

THE PROJECT:

How is co-ordinate regulation between neighbouring eukaryotic genes accomplished? How is the coregulation of groups of genes affected by non-coding genetic elements?

These are the questions at the heart of this PhD project that combines chromatin genetics, bioinformatics, research on non-coding RNAs and plant sciences to improve our fundamental understanding of eukaryotic gene regulation.

While prokaryotes have well described multicistronic transcripts (i.e. operons), in eukaryotes, such structures are the exception that prove the rule. Indeed, diverse examples for co-localised and coregulated functionally related genes have been identified in eukaryotes that resemble gene order in prokaryotes. Such eukaryotic gene clusters are associated with essential biological processes, from imprinting and embryonic development to antibiotic production. Co-ordinated expression is central to the activity of these clusters. But how is it that coordinated expression is achieved in eukaryotic gene clusters?

Here we will address this question by investigating the role of long noncoding RNAs in the regulation of clusters of genes in the model plant Arabidopsis thaliana. LncRNAs have emerged as important modulators of transcriptional activity across the eukaryotes. They have been shown to induce changes to chromatin modifications and three-dimensional chromosome structure.

In this interdisciplinary project, we will analyse the role of lncRNA in the transcriptional co-ordination on three levels. Firstly, the student will be trained in the bioinformatic analysis of large-scale datasets to generate a map of co-expressed neighbouring genes and their associated lncRNAs in A. thaliana. Secondly, the student will perform a focused functional analysis of the molecular role of lncRNAs at described gene clusters in A. thaliana. This will involve chromatin immunoprecipitation, RNA-DNA binding assays, chromosome conformation and gene expression analysis. Thirdly, a comprehensive evolutionary analysis of cluster-associated lncRNAs will be implemented. LncRNAs will be analysed on sequence, RNA structure and positional level across closely related plant species and animals. A machine learning approach will be devised to identify signatures that may define cluster associated lncRNAs.

The doctoral researcher will be based at the newly established Milner Centre for Evolution at the University of Bath and integrated into an ongoing collaboration between the Milner Centre and the National Laboratory of Genomics for Biodiversity (LANGEBIO), Irapuato, Mexico.

We are looking for an applicant who is curious about genetics and gene regulation and excited to apply both molecular and bioinformatics techniques. Practical skills in plant molecular biology/chromatin genetics and bioinformatics/coding are advantageous but not required and specialised training will be provided.

APPLICATIONS:

Applicants must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology.

Applications should be submitted on the University of Bath’s online application form for a PhD in Biosciences:
https://samis.bath.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=RDUBB-DT01&code2=0003

Please ensure that you quote the supervisor’s name and project title in the ‘Your research interests’ section. You may apply for more than one project if you wish but you should submit a separate personal statement relevant to each one.