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Evolutionary insights for engineering improved globin oxygen carriers


Institute of Integrative Biology

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Dr M Berenbrink , Dr J Madine 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/

The project is suited to a student with at least a good B.Sc. Upper Second in Biological or Life Sciences (particularly Biomedicine, Biochemistry, Molecular Biology, Bioinformatics, or Comparative Physiology).

Funding Notes

The project is open to both European/UK and International students. It is UNFUNDED and applicants are encouraged to contact the Principal Supervisor directly to discuss their application and the project.

Assistance will be given to applications who are applying to international funding schemes.

The successful applicant will be expected to provide the funding for tuition fees and living expenses as well as research costs of £3.000 per year.

A fee bursary may be available for well qualified and motivated applicants.

Details of costs can be found on the University website: https://www.liverpool.ac.uk/study/postgraduate-taught/finance/#living-expenses

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/

Davies H.A., Madine J., Middleton D.A. (2015). Comparison with amyloid-β reveal an aspartate residue that stabilizes fibrils of the aortic amyloid polypeptide medin, The Journal of Biological Chemistry 290: 7791-7803
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