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Bionic vesicles for enhanced performance of membrane proteins in biotechnology

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  • Full or part time
    Dr P Beales
    Dr Lars Jeuken
    Dr S Muench
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Membrane proteins are by far the most common target for existing and future pharmaceuticals, while their enzymatic properties hold great promise in biotechnology. We wish to expand on the application of membrane proteins in pharmaceutical research and biotechnology by creating bottom-up synthetic biology constructs with vastly enhanced functionality and longevity. This PhD project will develop hybrid systems that combine the stability of polymer systems with the biofunctionality of phospholipid biomembranes to create synthetic constructs with functional activity and durability appropriate for application of membrane proteins in novel technologies.
The student will learn skills in expression, purification, reconstitution and functional characterization of membrane proteins. Advanced biophysical techniques including confocal microscopy and cryo-TEM will be applied to gain detailed insights into the behaviour and properties of these proteins in hybrid membranes. A wide range of membrane proteins will be studied to investigate the generality of hybrid vesicles as a robust, biocompatible construct to enhance their stability and function. Hybrid vesicles will also be developed to specifically enhance the performance (functional activity and lifetime) of membrane proteins relevant to biotechnology and pharmaceutical industries. Examples include cytochrome P450s for pharmaceutical screening and respiratory enzymes (ubiquinol oxidase, F-ATPase, etc.) for proto-organelles in synthetic biology.

Funding Notes

BBSRC White Rose Mechanistic Biology DTP 4 year studentship.
Studentships covers UK/EU fees and stipend (c.£14,296) for 4 years to start in Oct 2017. Applicants should have/be expecting at least a 2.1 Hons. degree in a relevant subject. EU candidates require 3 years of UK residency in order to receive full studentship.
Not all projects advertised will be funded; the DTP will appoint a limited number of candidates via a competitive process and the projects selected by the successful candidates will be funded.
There are 2 stages to the application process. Please see our website for more information: http://www.fbs.leeds.ac.uk/postgraduate/phdopportunities.php

References

Khan S., Li M., Muench S.P., Jeuken L.J.C. and Beales P.A.; Durable Proteo-Hybrid Vesicles for the Extended Functional Lifetime of Membrane Proteins in Bionanotechnology. Chem. Commun. 52, 11020 - 11023 (2016)

Nam J., Vanderlick T.K. and Beales P.A.; Formation and dissolution of phospholipid domains with varying textures in hybrid lipo-polymersomes. Soft Matter 8, 7982-7988 (2012)

Nam J., Beales P.A. and Vanderlick T.K.; Giant Phospholipid/Block Copolymer Hybrid Vesicles: Mixing Behavior and Domain Formation. Langmuir 27 (1), 1-6 (2011)

Radu, V., Frielingsdorf, S., Evans, S.D., Lenz, O., Jeuken, L.J.C. (2014) Enhanced Oxygen-Tolerance of the Full Heterotrimeric Membrane-Bound [NiFe]-Hydrogenase of Ralstonia eutropha, J. Am. Chem. Soc., 136, 8512-8515.

Postis V, Rawson S, Mitchell JK, Lee SC, Parslow RA, Dafforn TR, Baldwin SA, Muench SP; The use of SMALPs as a novel membrane protein scaffold for structure study by negative stain electron microscopy Biochim Biophys Acta. 2015 Feb;1848(2):496-501

How good is research at University of Leeds in Chemistry?

FTE Category A staff submitted: 34.40

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