***Fully-funded 4 year BBSRC CASE studentship available to UK students to start in October 2015*** to work on "A tandem bio-chemo catalytic approach to the sustainable production of high performance coatings additives from glucose" in collaboration with Karen Wilson in Aston's Engineering & Applied Science School and Chemoxy Ltd. EU students are eligible to apply but will receive no stipend. Please contact Roslyn Bill for further details. Apply here.
We also welcome enquiries from PhD-qualified researchers from all countries outside the UK wishing to apply for a European Commission-funded Marie Sklodowska-Curie Individual Fellowship to come to work with us at Aston. Subject areas might include recombinant protein production in yeast, translational processes in recombinant protein production, bioprocessing and the regulation of aquaporin water channels. Please contact Roslyn Bill for further details.
Membrane proteins play pivotal roles in all cellular functions. These include the transport of nutrients, the export of toxins and cell-cell interactions. They are also ubiquitous: ~30% of all proteins in all cells are membrane proteins. Consequently they are already key drug targets, with the majority of prescription pharmaceuticals on the market being targeted to this class of protein. Unfortunately, however, they are neither naturally abundant nor stable, which means that in the vast majority of cases extracting them from natural sources is not a viable option in order to study their structures, functions and biochemistry.
A main theme of our research activity is developing yeast as a “cell factory” to make membrane proteins in sufficient quantity and of appropriate quality for further study. Our approach is to move away from “trial and error” and to rationalize recombinant protein production by understanding the host cell response to it. We aim to:
- increase the volumetric yield – Microb Cell Fact. 2010, 9:47;
- increase the yield “per cell” – BMC Genomics. 2008, 9:365; Microb Cell Fact. 2009, 8:1; Microb Cell Fact. 2009, 8:35; and
- understand the molecular mechanisms involved – Nat Biotechnol. 2011, 29: 335-340.
Our review in Biochem Soc Trans provides a good overview of our approach – see Biochem Soc Trans. 2011, 39: 719-723.
To listen to an interview on BBC Midlands Today click here. To see a podcast on what we do, click here. Our yeast engineering work is also highlighted in a recent meeting report and in The New Optimists - click here to see the interview
A second theme of our work is examining in detail the regulation of water channel proteins (aquaporins), which is one of the protein families we produce in our yeast cell factories and are of interest as novel drug targets. We recently showed that AQP1 is regulated by extracellular water availability (Biochemistry. 2010, 49:821-3). This work was featured on the front cover of its issue, and as part of the 50th birthday cover. To listen to a podcast on our work on membrane proteins more generally click here.
To read more about our work on G protein-coupled receptors, click here* and here.
We acknowledge EPSRC, BBSRC, the Technology Strategy Board, AstraZeneca Ltd, Alpha Biologics Ltd, Applikon Biotechnology, Johnson & Johnson, Glycoform Ltd, GlaxoSmithKline, Polytherics Ltd, Sauflon Ltd and the European Commission for their support.
We have co-ordinated three Framework Programme 6 projects: European Membrane Protein Consortium (E-MeP), E-MeP-Lab and OptiCryst. We were a partner of the Framework Programme 7 EDICT project.We are part of the IMI-funded ENABLE project.
We are currently two postdoctoral fellows, one Marie Sklodowska-Curie International Incoming Fellow, four PhD students and a placement student working with OPPF-UK.
Dr Sarah Routledge is a BBSRC-funded postdoctoral fellow supported by a project in collaboration with Professor David Poyner, Aston University and Professors Mark Wheatley and Tim Dafforn, University of Birmingham
Dr Stephanie Cartwright is a European Commission funded postdoctoral fellow working in collaboration with Professor Justin MacDonald, University of Calgary, Canada
Professor Justin MacDonald, University of Calgary, Canada, is an International Incoming Fellow visiting our laboratory with funding from the European Commission
Ms Michelle Clare is a 4th year PhD student supported by a BBSRC CASE studentship with Johnson & Johnson
Ms Anjana Patel is a 2nd year PhD student supported by a BBSRC CASE studentship with Sauflon Ltd
Ms Lina Mikaliunaite is a 2nd year PhD student supported by a BBSRC CASE studentship with GlaxoSmithKline Ltd
I also co-supervise Mr David Hardy with Dr Alice Rothnie; David is a 1st year PhD student supported by a BBSRC CASE studentship with Calixar
Mr Bilaal Salad is a placement student working with OPPF-UK
Dr Marvin Dilworth, supported by a BBSRC CASE studentship with Glycoform Ltd, passed his viva on 23rd June 2014
Dr Zharain Bawa, supported by a BBSRC CASE studentship with AstraZeneca Ltd, passed her viva on 3rd June 2014 and took up a poaition at Public Health England
Dr Debasmita Sarkar, a postdoctoral fellow supported by Aston University in collaboration with OPPF-UK, took up a BBSRC-funded research fellow position at Aston University, Birmingham
Dr Stephanie Cartwright, supported by a BBSRC targeted priority studentship in ageing, passed her viva on 15th August 2013 and took up a European-Commission-funded postdoctoral position at Aston University, Birmingham
Ms Charlie Bland, a research technician supported the EDICT project, took up a research technician post at Aston Research Centre for Healthy Ageing
Dr Matthew Conner, a postdoctoral researcher supported by the EDICT project, took up a lectureship at Sheffield Hallam University
Dr Sarah Routledge, supported by an EPSRC CASE studentship with Applikon Biotechnology, passed her viva on 2nd March 2012 and took up a BBSRC-funded postdoctoral position at Aston University, Birmingham
Dr Nicklas Bonander, a postdoctoral researcher supported by the OptiCryst project, took up a position at Chalmers University of Technology, Gothenburg
Dr Nagamani Bora, a postdoctoral researcher supported by the Technology Programme, funded through EPSRC, in collaboration with Glycoform Ltd and Polytherics Ltd, took up a senior lectureship at De Montfort University
Dr Richard Darby, a former postdoctoral researcher supported by the E-MeP project, took up a position at the John Radcliffe Hospital, University of Oxford
Dr Ljuban Grgic, a former postdoctoral researcher supported by the E-MeP project, took up a position at the MRC Mitochondrial Biology Unit, University of Cambridge
Dr Mohammed Jamshad, a former postdoctoral researcher supported by the E-MeP project, took up a position at the School of Biosciences, University of Birmingham
Dr William Holmes, supported by an EPSRC CASE award with Alpha Biologics, passed his viva on 11th March 2009 and took up a position at MedImmune, Cambridge
M Eric Bourguignon, a former European Research Project Officer supported by E-MeP, took up a position as a project administrator at the Technical University in Munich
Dr Daniela Tomescu is a former European Research Project Officer supported by E-MeP, took up a position as a project administrator at the University of Cambridge
Corresponding authorship is highlighted with an asterisk (*)
For a full listing go to my ResearcherID page at http://www.researcherid.com/rid/D-4554-2012 (requires institutional login)
See also my Google Scholar Profile
Recommended reading! Recombinant Protein Production in Yeast, Bill RM, Ed, in the Methods in Molecular Biology series, Springer
Prielhofer R, Cartwright SP, Graf AB, Valli M, Bill RM*, Mattanovich D* and Gasser B (2015)
Pichia pastoris regulates its gene-specific response to different carbon sources at the transcriptional, rather than the translational, level
BMC Genomics, in press
Jamshad M, Charlton J, Lin Y-P, Routledge SJ, Bawa Z, Knowles TJ, Overduin M, Dekker N, Dafforn TR, Bill RM, Poyner DR, Wheatley M* (2015)
G-protein-coupled receptor solubilization and purification for biophysical analysis and functional studies in the total absence of detergent
Biosci Rep, in press
Bill RM* (2014)
Recombinant protein sub-unit vaccine synthesis in microbe: a role for yeast?
J Pharm Pharmacol, in press
Bawa Z, Routledge SJ, Jamshad, Clare M, Sarkar D, Dickerson I, Ganzlin M, Poyner DR, Bill RM* (2014)
Functional recombinant protein is present in the pre-induction phases of Pichia pastoris cultures when grown in bioreactors, but not shake-flasks
Microb Cell Fact 13(1):127
Routledge SJ*, Poyner DR, Bill RM (2014)
Antifoams: the overlooked additive?
Pharm. Bioprocess; 2(2), 103–106
Bill RM* (2014)
Playing catch-up with Escherichia coli: using yeast to increase success rates in recombinant protein production experiments
Front Microbiol; 5:85
Day RE, Kitchen P, Owen D, Bland C, Marshall L, Conner AC, Bill RM*, Conner MT (2013)
Human aquaporins: Regulators of transcellular water flow
Biochim Biophys Acta; 1840(5):1492-506
Bonander N, Jamshad M, Oberthür D, Clare M, Barwell J, Hu K, Farquhar MJ, Stamataki Z, Harris HJ, Dierks K, Dafforn TR, Betzel C, McKeating JA and Bill RM* (2013)
Production, purification and characterization of recombinant, full-length human claudin-1
PLOS ONE, 8(5): e64517 Hipkiss AR, Cartwright SP, Bromley C, Gross SR and Bill RM* (2013)
Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?Chem Cent J, 7; 38 - see also the Chem Cent J blog and Daily Express coverage!
Conner AC, Bill RM, Conner MT (2013)
An emerging consensus on aquaporin translocation as a regulatory mechanism
Mol Membr Biol, 30; 101-112
Bonander N, Bill RM* (2012)
Optimising yeast as a host for recombinant protein production
Methods Mol Biol, 866; 1-9
Darby RAJ, Cartwright SP, Dilworth MV, Bill RM* (2012)
Which species shall I choose? Saccharomyces cerevisiae versus Pichia pastoris
Methods Mol Biol, 866; 11-23
Routledge SJ, Bill RM (2012)
The effect of antifoam addition on protein production yield
Methods Mol Biol, 866: 87-97
Bora N, Bawa N, Bill RM, Wilks MDB (2012)
The implementation of a design of experiments strategy to increase recombinant protein yields in yeast
Methods Mol Biol, 866: 115-127
Cartwright SP, Bill RM*, Hipkiss AR* (2012)
L-Carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner
PLOS ONE, 7(9): e45006
Conner MT, Conner AC, Bland CE, Taylor LHJ, Brown JEP, Parri HR, Bill RM* (2012)
Rapid aquaporin translocation regulates cellular water flow: the mechanism of hypotonicity-induced subcellular localization of the aquaporin 1 water channel
J Biol Chem,287:11516-11525; evaluated by F1000 as a "must read"
Kitson SM, Mullen W, Cogdell RJ, Bill RM, Fraser NJ (2011)
GPCR production in a novel yeast strain that makes cholesterol-like sterols
Öberg F, Sjöhamn J, Conner MT, Bill RM, Hedfalk K (2011)
Improving recombinant eukaryotic membrane protein yields in Pichia pastoris: the importance of codon optimisation and clone selection
Mol Membr Biol, 28:398-411
Bill RM*, Henderson PJF, Iwata S, Kunji ERS, Michel H, Neutze R, Newstead S, Poolman B, Tate CG and Vogel H (2011)
Overcoming barriers to membrane protein structure determination
Nat Biotechnol, 29: 335-340.
Routledge SJ, Hewitt CJ, Bora N and Bill RM* (2011)
Antifoam addition to shake flask cultures of recombinant Pichia pastoris increases yield
Microbial Cell Factories, 10,17.
Garcia-Caballero A, Gavira J, Pineda-Molina E, Chayen N, Govada L, Kurshid S, Saridakis E, Boudjemline A, Swann M, Shaw Stewart P, Briggs R, Kolek S, Oberthur D, Dierks K, Betzel C, Santana M, Hobbs J, Thaw P, Savill T, Mesters J, Hilgenfeld R, Bonander N and Bill RM* (2011)
Optimization of protein crystallization: the OptiCryst project
Cryst Growth Des, 11: 2112-2121.
Bawa Z, Bland CE, Bonander N, Bora N, Cartwright SP, Conner MT, Darby RAJ, Dilworth MV, Holmes WJ, Jamshad M, Routledge SJ, Gross SR and Bill RM* (2011)
Understanding the yeast host cell response to recombinant membrane protein production
Biochem Soc Trans, 39: 719-723. and 39:1113
Jamshad M, Lin YP, Knowles TJ, Parslow RA, Harris C, Wheatley M, Poyner DR, Bill RM, Thomas ORT, Overduin M and Dafforn TR (2011)
Surfactant-free purification of membrane proteins with intact native membrane environment
Biochem Soc Trans, 39: 813-8.
Ashe MP and Bill RM* (2011)
Mapping the yeast host cell response to recombinant membrane protein production: relieving the biological bottlenecks.
Biotechnol J, 6: 707-14.
Bonander N, Jamshad M, Hu K, Farquhar MJ, Stamataki Z, Balfe P, McKeating JA and Bill RM* (2011)
Structural characterisation of CD81/Claudin-1 Hepatitis C virus receptor complexes.
Biochem Soc Trans, 39: 537-40.
Ferndahl C, Bonander N, Logez C, Wagner R, Gustafsson L, Larsson C, Hedfalk K, Darby RAJ and Bill RM* (2010)
Increasing cell biomass in Saccharomyces cerevisiae increases recombinant protein yield: the use of a respiratory strain as a microbial cell factory.
Microbial Cell Factories, 9, 47.
Conner MT, Conner AC, Brown JE and Bill RM* (2010)
Membrane trafficking of AQP1 is mediated by PKC via microtubules and regulated by tonicity.
Biochemistry, 49: 821-823 as featured on the front cover of the journal and the 50th birthday edition
Bonander N and Bill RM* (2009)
Relieving the first bottleneck in the drug discovery pipeline: using array technologies to rationalise membrane protein production
Expert Rev Proteomics, 6, 501-5
Holmes WJ, Darby RAJ, Wilks MDB, Smith R and Bill RM* (2009)
Developing a scalable model of recombinant protein yield from Pichia pastoris: the influence of culture conditions, biomass and induction regime
Microbial Cell Factories, 8, 35.
Chan KLA, Govada L, Bill RM, Chayen NE and Kazarian SG (2009)
ATR-FTIR spectroscopic imaging of protein crystallization
Anal Chem, 81, 3769–3775 as featured on the front cover of the journal
Bonander N, Darby RAJ, Grgic L, Bora N, Wen J, Brogna S, Poyner DR, O’Neill MAA and Bill RM* (2009)
Altering the Ribosomal Subunit Ratio in Yeast Maximises Recombinant Protein Yield
Microbial Cell Factories, 8,10.
Bonander N, Ferndahl C, Mostad P, Wilks M D B, Chang C, Showe L, Gustafsson L, Larsson C, Bill RM* (2008)
Transcriptome analysis of a respiratory Saccharomyces cerevisiae strain suggests the expression of its phenotype is glucose insensitive and predominantly controlled by Hap4, Cat8 and Mig1
BMC Genomics, 9, 365.
- Jamshad M, Rajesh S, Stamataki Z, McKeating JA, Dafforn T, Overduin M and Bill RM* (2008)
Structural Characterization of Recombinant Human CD81 Produced in Pichia pastoris
Prot Expr Purif, 57, 206-16.
- Nyblom M, Öberg F, Petersson-Lindkvist K, Findlay H, Wikström J, Karlsson A, Hansson, Booth PJ, Bill RM, Neutze R and Hedfalk K (2007)
Exceptional Overproduction of a Functional Human Membrane Protein
Prot Expr Purif, 56, 110-120.
- Fantoni A, Bill RM, Gustafsson L and Hedfalk K (2007)
Improved Yields of Full-length Functional Human FGF1 can be Achieved using the Methylotrophic Yeast Pichia pastoris
Prot Expr Purif, 52, 31-39.
- Aricescu A R, Assenberg R, Bill R M, Busso D, Chang V T, Davis S J, Dubrovsky A, Gustafsson L, Hedfalk K, Heinemann U, Jones I M, Ksiazek D, Lang C, Maskos K, Messerschmidt A, Macieira S, Peleg Y, Perrakis A, Poterszman A, Schneide r G, Sixma T K, Sussman J L, Sutton G, Tarboureich N, Zeev-Ben-Mordehai T and Jones E Y (2006)
Eukaryotic Expression: Developments for Structural Proteomics
Acta Cryst, D62, 1114-1124. Download the pdf here.
- Petterson N, Hagström J, Bill R M and Hohmann S (2006)
Expression of Heterologous Aquaporins for Functional Analysis in Saccharomyces cerevisiae
Curr Genet, 50, 247-55.
- Saidijam M, Benedetti G, Ren Q, Xu Z, Hoyle C J, Palmer S L, Ward A, Bettaney K E, Szakonyi G, Meuller J, Morrison S, Pos M K, Butaye P, Walravens K, Langton K, Herbert R B, Brown M H, Skurray R A, Paulsen I T, O’Reilly J, Rutherford N G, Bill R M and Henderson P J F (2006)
Microbial Drug Efflux Proteins of the Major Facilitator Superfamily
Curr Drug Targets, 7, 793-811.
- Henricsson C, de Jesus Ferreira MC, Hedfalk K, Elbing K, Larsson C, Bill R M, Norbeck J, Hohmann S and Gustafsson L (2005)
Engineering of a Novel Saccharomyces cerevisiae Wine Strain with a Respiratory Phenotype at High External Glucose Concentrations.
Appl Env Microbiol, 71, 6185-92.
- Saidijam M, Bettaney KE, Szakonyi G, Psakis G, Shibayama K, Suzuki S, Clough JL, Blessie V, Abu-Bakr A, Baumberg S, Meuller J, Hoyle CK, Palmer SL, Butaye P, Walravens K, Patching SG, O'Reilly J, Rutherford NG, Bill RM, Roper DI, Phillips-Jones MK, Henderson PJ (2005)
Active Membrane Transport and Receptor Proteins from Bacteria.
Biochem Soc Trans, 33, 867-72.
- Bonander N, Hedfalk K, Larsson C, Mostad P, Chang C, Gustafsson L, Bill RM* (2005)
Design of Improved Membrane Protein Production Experiments: Quantitation of the Host Response
Protein Sci, 14, 1729-40.
- Karlgren S, Pettersson N, Nordlander B, Mathai J C, Brodski J L, Zeidel M L, Bill R M, Hohmann S (2005)
Conditional Osmotic Stress in Yeast: A System to Study Transport Through Aquaglyceroporins and Osmostress Signalling.
J Biol Chem, 280, 7186-93.
A full listing is also available on Pubmed
- Bill RM, Bonander N, Darby RAJ, Grgic L
Protein Expression System.
UK Patent Application Number 0813253.2, filed 18th July 2008.
- Bill R M, Boles E, Gustafsson L, Hohmann S, Larsson C and Otterstedt K
Recombinant Saccharomyces cerevisiae Expressing Chimeric Glucose Transporters.
Patent Application Number WO0200880, published 3rd January 2002.
- Bill R M, Revers L and Wilson I B H: Protein Glycosylation.
Kluwer Academic Publishers, Norwell, 1998, 508 pages.
- Darby R A J, Jamshad M, Grgic L, Holmes W J and Bill R M (2010)
Production of Recombinant G-protein-coupled Receptor in Yeast for Structural and Functional Analysis.
In: G-protein Coupled Receptors: Essential Methods (David Poyner and Mark Wheatley, Eds). John Wiley and Sons, Chichester, UK, 2010, Chapter 5, p85-107.
- Roach PCJ, O’Reilly J, Norbertczak HT, Hope RJ, Venter H, Patching SG, Jamshad M, Stockley PG, Baldwin SA, Herbert RB, Rutherford NG, Bill RM and Henderson PJF (2008)
Equipping a Research-Scale Fermentation Laboratory for Production of Membrane Proteins.
In: Practical Fermentation Technology (Brian McNeil and Linda Harvey, Eds.). John Wiley and Sons, Chichester, UK, Chapter 3, p 37-67.
- Clough J, Saidijam M, Bettaney K, Szakonyi G, Meuller J, Suzuki S, Bacon M, Barksby E, Ward A, Gunn F, O’Reilly J, Rutherford N, Bill RM and Henderson PJF (2006)
Prokaryote Membrane Transport Proteins: Amplified Expression and Purification.
In: Structural Genomics on Membrane Proteins (Kenneth Lundstrom, Ed.). Taylor & Francis, Boca Raton, p21-42.
- Kayingo G, Bill R M, Calamita G, Hohmann S and Prior B A (2001)
Microbial Water and Glycerol Channels: Function, Regulation and Physiological Roles.
In: Aquaporins (Peter Agre, Stefan Hohmann, Soren Nielsen, Eds.). Academic Press, New York, p335-370.
- Bill R M, Hedfalk K, Karlgren S, Rydström J and Hohmann S (2000)
Functional Analysis of the Unusual Signature Motifs of the Yeast MIP Channel, Fps1p.
In: Molecular Biology and Physiology of Water and Solute Transport: the MIP Family of Channel Proteins (Stefan Hohmann, Soren Nielsen Eds.). Kluwer/Plenum, New York, p3-11.
- Hedfalk K, Bill R M, Hohmann Sand Rydström J (2000)
Overexpression and Purification of the Glycerol Transport Facilitators, Fps1p and GlpF, in S. cerevisiae and E. coli
In Molecular Biology and Physiology of Water and Solute Transport: the MIP Family of Channel Proteins (Stefan Hohmann, Soren Nielsen Eds.). Kluwer/Plenum, New York, p29-34.