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  (BBSRC DTP) Complexity of heart development arising from evolution of signalling systems


   Faculty of Biology, Medicine and Health

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  Dr Kathryn Hentges, Dr D Talavera, Prof Simon Lovell  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

Protein families grow or shrink in size during evolution due to gene duplication and gene loss events. These events provide opportunities for protein function specialisation or innovation. No protein families have experienced more dramatic expansions during the evolution of multicellular organisms than those involved in the sensing, integration and response to stimuli. These protein families, which we term signalling systems, include ligands, signal receptors and transducers, and transcription factors. Expansion and contraction of protein families as well as sequence variation occurring within particular lineages may have a huge effect on the signalling pathways, and the subsequent activation/inhibition of biological processes. Achieving an overall understanding of the evolution of signalling systems requires not only studying the evolution of individual genes, but also understanding the variation of the system as a whole from the most upstream to the most downstream elements.

The cardiovascular system is critical for the transport of nutrients, signals and gases to and from the cells in the body. The vast majority of animal phyla have either an open or a closed circulatory system. Circulation requires a muscular organ capable of pumping the fluid throughout the body: the heart. Notably, there are many different types of hearts in the animal kingdom in spite of the fact that some of the key regulators of heart development are found from fruitfly to human. We are interested in understanding how evolution of particular signalling systems has shaped cardiac development throughout the evolution of vertebrates.

The project will enhance our understanding of the evolution of signalling systems involved in cardiac development, and how complexity may arise from a stochastic combination of gene duplication and deletion events. The student will use a mix of lab and computational approaches including cell culture, phylogenetics and network analyses, and structural bioinformatics. The project builds on the existing knowledge and complementary expertise of the different laboratories involved. It represents an ideal opportunity for an individual with a keen interest in molecular evolution and development biology, and eagerness to learn both experimental and computational methodologies.

https://www.research.manchester.ac.uk/portal/kathryn.hentges.html
https://www.research.manchester.ac.uk/portal/david.talavera.html
https://www.research.manchester.ac.uk/portal/simon.lovell.html

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website www.manchester.ac.uk/bbsrcdtpstudentships

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

• Putnam, N.H., et al., The amphioxus genome and the evolution of the chordate karyotype. Nature, 2008. 453(7198): p. 1064-71.
• Ames, R.M., et al., Determining the evolutionary history of gene families. Bioinformatics, 2012. 28(1): p. 48-55.
• Talavera, D. et al., Covariation Is a Poor Measure of Molecular Coevolution. Mol Biol Evol, 2015. 32(9): p. 2456-68.
• Ramos-Vicente, D. et al., Metazoan evolution of glutamate receptors reveals unreported phylogenetic groups and divergent lineage-specific events. eLife, 2018. 7:e35774