Professor Roslyn M. Bill

Professor of Biotechnology

School of Life & Health Sciences
email: r.m.bill@aston.ac.uk
telephone:  +44 121 204 4274  
fax: +44 121 204 4175

Research Convenor for the Molecular & Cell Biology Research Group
Member of the Biomedical Sciences Research Area
Member - Aston Research Centre for Healthy Ageing  

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We welcome enquiries from PhD-qualified researchers from all countries outside the UK wishing to apply for a Marie Curie Fellowship to come to work with us at Aston; the next call opens on 14th March with a deadline of 14th August 2013. There are two Fellowship Schemes available:

• One for early- to mid-career researchers of any nationality currently working in Europe (Intra-European fellowship, IEF); 
  
• One for researchers at mid-career plus working in any country outside of Europe (International Incoming Fellowship, IIF).

Subject areas might include translational processes in recombinant protein production, bioprocessing and  the regulation of aquaporin water channels. Please contact Roslyn Bill for further details.

Research Interests

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 50^th birthday cover. To listen to a podcast on our work on membrane proteins more generally click here.

We acknowledge EPSRC, BBSRC, the Technology Strategy Board, AstraZeneca Ltd, Alpha Biologics Ltd, Applikon Biotechnology, Johnson & Johnson, Glycoform Ltd, Polytherics 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 are also a partner of the Framework Programme 7 EDICT project.

Current Group Members

We are currently two postdoctoral fellows, five PhD students and a technician.

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 (left)

Dr Debasmita Sarkar is a postdoctoral fellow supported by Aston University in collaboration with Isis Innovation (not shown)

Dr Nagamani Bora is a postdoctoral researcher supported by the Technology Programme, funded through EPSRC, in collaboration with Glycoform Ltd and Polytherics Ltd (not shown)

Ms Charlie Bland is a research technician supported by Aston Research Centre for Healthy Ageing (not shown)

Ms Zharain Bawa is a 3rd year PhD student supported by a BBSRC CASE studentship with AstraZeneca Ltd (right)

Ms Stephanie Cartwright is a 3rd year PhD student supported by a BBSRC targeted priority studentship in ageing (second from left)

Ms Michelle Clare is a 2nd year PhD student supported by a BBSRC CASE studentship with Johnson & Johnson (not shown)

Mr Marvin Dilworth is a 1st year PhD student supported by a BBSRC CASE studentship with Glycoform Ltd (not shown)

I also co-supervise Mr Gabriel Kuteyi, a 3rd year PhD student with Professor David Poyner (not shown)

Former Group Members

Dr Matthew Conner, a postdoctoral researcher supported by the EDICT project, took up a lectureship at Sheffield Hallam University (second from right)

Dr Sarah Routledge, supported by an EPSRC CASE studentship with Applikon Biotechnology, passed her viva on 2^nd March 2012 and took up a BBSRC-funded postdoctoral position at Aston University, Birmingham (left)

Dr Nicklas Bonander, a postdoctoral researcher supported by the OptiCryst project, took up a position at Chalmers University of Technology, Gothenburg 

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 (shown third from right)

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 11^th 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

Recent Publications

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

Just published - Recombinant Protein Production in Yeast, Bill RM, Ed, in the Methods in Molecular Biology series, Springer

• 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
  Methods, 55:287-92

• 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

Patents

• Bill RM, Bonander N, Darby RAJ, Grgic L
  Protein Expression System.
  UK Patent Application Number 0813253.2, filed 18^th 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.

Book

• Bill R M, Revers L and Wilson I B H: Protein Glycosylation.
  Kluwer Academic Publishers, Norwell, 1998, 508 pages.

Book Chapters

• 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.