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EASTBIO: Exploiting big-data genomics to understand the parallel evolution of gene operons in eukaryotes


School of Medicine, Medical Sciences & Nutrition

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Dr J Pettitt , Dr B Mueller , Dr M Wenzel , Prof I Stansfield No more applications being accepted Competition Funded PhD Project (European/UK Students Only)

About the Project

Supervisors:

Dr Jonathan Pettitt (University of Aberdeen)
https://www.aberdeenwormlab.org/

Dr Berndt Mueller (University of Aberdeen)
https://www.aberdeenwormlab.org/

Dr Marius Wenzel (University of Aberdeen)
https://www.abdn.ac.uk/people/marius.wenzel

Professor Ian Stansfield (University of Aberdeen)
https://www.abdn.ac.uk/people/i.stansfield

A fascinating question in evolutionary biology is how particular phenotypes have evolved multiple times independently in distantly related lineages in the tree of life. Striking examples are the parallel evolution of flight in birds and mammals or adaptations to aquatic life styles in fish and mammals. Comparing the fundamental developmental and genetic underpinning of such recurrent evolution is important, because it reveals the available pathways and constraints for evolutionary change.
An intriguing example of parallel evolution at the molecular level is the occurrence of eukaryotic operons. This gene-expression strategy has evolved many times in several eukaryotic lineages and allows the expression of a set of neighbouring genes as a single transcription unit. The RNA produced by eukaryotic operons must be processed into single-gene transcripts for translation in the cytoplasm. Since this strategy evolved as a modification of the highly conserved eukaryotic RNA splicing machinery, studying the diversity of eukaryotic operon gene expression mechanisms can tell us about the functional evolutionary constraints that exist within the eukaryotic cell.
This project asks what elements of eukaryotic operonic gene expression are functionally constrained or variable across a broad range of eukaryotes. The project will initially involve comparative computational analysis of publicly available genomes and transcriptomes. The student will develop analysis pipelines in a Linux and R-based environment with a focus on processing high-throughput sequence data, genome assembly, genome annotation and statistical comparative genomics. Pilot data that validated this approach in nematode species is available and full training will be provided for all computational approaches.

In parallel to this, we will investigate the rules underlying the evolution of operonic RNA processing using a yeast-based experimental evolution system. We will use forced evolution in the laboratory to select for increases in the efficiency operon processing, exploiting synthetic biology approaches in a yeast strain expressing nematode RNA factors that we have developed to specifically study this problem. This will allow us to identify the changes that occur during the emergence of polycistronic RNA processing and complement our studies of organisms in which this process is already well established.

The study of operonic gene expression across the Eukarya offers a unique opportunity to investigate the constraints that operate during the diversification of a conserved molecular process. Many of the eukaryote groups that employ operons as an essential gene expression strategy contain important human, animal and plant pathogens. Thus, these studies will also highlight potential avenues for the development of novel therapeutic interventions to treat parasitic infections.

Application Procedure:
http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO application form, along with academic transcripts and CV to Alison McLeod at [Email Address Removed]. Two references should be provided by the deadline using the EASTBIO reference form. Please advise your referees to return the reference form to [Email Address Removed].

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership. This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body. Queries on eligibility? Email Alison McLeod ([Email Address Removed]).

Candidates should have (or expect to achieve) a minimum of a First Class Honours degree in a relevant subject. Applicants with a minimum of a 2:1 Honours degree may be considered provided they have a Distinction at Masters level.

References

Maeso I, Roy SW, Irimia M. Widespread recurrent evolution of genomic features. Genome Biol Evol. 2012;4: 486–500.

Wenzel MA, Johnston C, Müller B, Pettitt J, Connolly B. Deep evolutionary origin of nematode SL2 trans-splicing revealed by genome-wide analysis of the Trichinella spiralis transcriptome [Internet]. bioRxiv. 2019. p. 642082. doi:10.1101/642082


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