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Bionic protocells for enhanced performance of membrane proteins in biotechnology

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  • Full or part time
    Dr P Beales
    Prof 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

Protocells are seen as a stepping-stone to understanding the origin of life and are being developed to generate novel cell-like biotechnologies. They are typically vesicles made from phospholipids, which have short lifespan. In this project you will use principles of synthetic biology to enhance the stability of protocells by creating hybrid bionic systems that combine advantages of liposomes and polymersomes. Incorporation of membrane proteins will provide transport, catalytic and signalling functionalities with potential for wide-ranging applications.

You will build on recent advanced in hybrid vesicles as a durable membrane protein reconstitution system: we recently demonstrated a tenfold increase in functional lifetime of a respiratory enzyme compared to conventional proteoliposomes. A wider range of membrane proteins will be characterized in hybrid vesicles, in particular protocells will be developed for membrane proteins relevant to biotechnology and pharmaceutical industries. Multiple proteins will be incorporated into protocells resulting in emergent phenomena, for example combining respiratory enzymes (ubiquinol oxidase, F-ATPase, etc.) for proto-organelles in synthetic biology. You will learn skills in expression, purification, reconstitution and functional characterization of membrane proteins. Advanced biophysical characterization techniques including confocal microscopy and cryo-TEM will be applied to gain detailed insights into the behaviour of these proteins in hybrid membranes.

Funding Notes

BBSRC White Rose Mechanistic Biology DTP 4 year studentship.

Studentships covers UK/EU fees and stipend (c.£14,553) for 4 years to start in Oct 2018. 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

Beales P.A., Khan S., Muench S.P. and Jeuken L.J.C.; Durable vesicles for reconstitution of membrane proteins in biotechnology. Biochem. Soc. Trans. 45(1), 15-26 (2017).

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.

Li, M., Jørgensen, S.K., McMillan, D.G.G., Krzemiński, L., Daskalakis, N.N., Partanen, R.H., Tutkus, M., Tuma, R., Stamou, D., Hatzakis, N.S., Jeuken, L.J.C. Single enzyme experiments reveal a long-lifetime proton leak state in a heme-copper oxidase, J. Am. Chem. Soc., 137, 6055-16063 (2015).

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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