Evolutionary insights for engineering improved globin oxygen carriers at University of Liverpool on FindAPhD.com

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Dr M Berenbrink Applications accepted all year round Self-Funded PhD Students Only

About the Project

Around 2 million red blood cell units at a cost of 120.00 GBP per unit are transfused annually in England alone (http://www.nhsbt.nhs.uk/what-we-do/blood-transfusion/). These costs, together with a shortage of donors and inherent infection risks, have led to the drive for development of artificial, haem-based oxygen carriers.

Myoglobin, the oxygen-binding protein in muscle, is a prototype for developing haem-based oxygen carriers. The problem of myoglobin production in recombinant expression systems is that the protein tends to form non-functional and even dangerous aggregates at the high concentrations required for industrial production.

Research at Liverpool has revealed that myoglobin in diving mammals and birds has special properties that allow it to maintain its stability and proper function at much higher cellular concentrations than in terrestrial mammals. See: https://www.youtube.com/watch?v=vjk6e3kSNuY

The aim of this project is to determine the molecular mechanism(s) behind the increased stability and maximal concentration of myoglobin in diving animals and to use this knowledge for the development of an improved oxygen carrier. This project provides multi-disciplinary training in bioinformatics and genomics, biochemical and biophysical techniques and evolutionary physiology and ecology.

For further information see the website: https://www.liverpool.ac.uk/integrative-biology/

To apply:
The email form below can be used for both enquiries and full applications (CV and covering letter). Informal enquiries are openly encouraged.

Funding Notes

This is project is available to self-funded students. The PhD will start in October 2017. Applicants should have, or be expecting to receive, a least 2.1 Hons degree (or equivalent) in a relevant subject.

A fees bursary may be available.

References

Scott Mirceta, Anthony V. Signore, Jennifer M. Burns, Andrew R. Cossins, Kevin L. Campbell, Michael Berenbrink (2013). Evolution of mammalian diving capacity traced by myoglobin net surface charge. Science 340, 1234192. DOI: 10.1126/science.1234192

The work is show-cased in a video featured on the BBSRC website: http://webarchive.nationalarchives.gov.uk/20160108075453/http://www.bbsrc.ac.uk/news/health/2013/130614-pr-study-diving-mammals-underwater-endurance/

The work exemplifies the world class science aspired to in this studentship and summaries the all-pervasive integrative approach that links genotypes to the phenotypes of organisms from the molecular, to the cellular, organ system, and whole organism level of biological organisation, including environmental and evolutionary dimensions. It demonstrates the use of ancestral sequence reconstruction and modelling of protein net surface charge.

Where will I study?

University of Liverpool

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Evolutionary insights for engineering improved globin oxygen carriers

University of Liverpool Institute of Integrative Biology