School of Life & Health Sciences email: email@example.com telephone: +44 121 204 4274 fax: +44 121 204 4175
Molecular Biomedical Research
Aston Research Centre for Healthy Ageing (ARCHA)
PhD studentships available! Please contact Roslyn Bill for further details.
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.
2016-date LHS Associate Dean Research
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:
Our review in Current Opinion in Structural Biology provides a good overview of our approach.
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 The New Optimists - click here to see the interview. Some of our favourite microbes are yeasts. Click here to read about fantastic yeasts and where to find them! Click here to see an animation describing our work on making recombinant enzymes to convert waste products into useful chemicals.
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 were the first to show 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. Click here to watch my lecture on cell membranes, how they control the flow of water into and out of cells and what happens when that goes wrong!
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 three postdoctoral fellows, five PhD students and a placement student.
Dr Michelle Clare is a BBSRC-funded postdoctoral fellow supported by a project in collaboration with Drs Alex Cameron and Corinne Smith, Warwick University, and Professor Jane MacKeating, University of Birmingham
Dr Stephanie Cartwright is a European Commission funded postdoctoral fellow working on the ENABLE project
Dr Pinar Karagoz is a postdoctoral fellow funded by BBSRC's FoodWasteNet NiBB in collaboration with Professor Karen Wilson.
Ms Anjana Patel is a 3rd year PhD student supported by a BBSRC CASE studentship with Sauflon Ltd
Ms Lina Mikaliunaite is a 3rd year PhD student supported by a BBSRC CASE studentship with GlaxoSmithKline Ltd
I also co-supervise 2nd year PhD students, Mr David Hardy and Mr Floren Low, with Dr Alice Rothnie; David is supported by a BBSRC CASE studentship with Calixar
Miss Ravneet Kaur is a first year PhD student supported by a BBSRC CASE studentship with Chemoxy Ltd, in collaboration with Professor Karen Wilson
Miss Simran Lallie is a placement student working with Lina Mikaliunaite
Dr Marvin Dilworth, supported by a BBSRC CASE studentship with Glycoform Ltd, passed his viva on 23rd June 2014 and took up a position at King's College London with Professor Paula Booth
Dr Zharain Bawa, supported by a BBSRC CASE studentship with AstraZeneca Ltd, passed her viva on 3rd June 2014 and took up a position 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
Analyzing Recombinant Protein Production in Pichia pastoris with Targeted Proteomics Bill, R. M., Ulke-Lemée, A., Cartwright, S. P., Far, R., Kim, J. & MacDonald, J. A., 9 Feb 2019,
Recombinant Protein Production in Yeast. Gasser, B. & Mattanovich, D. (eds.). Humana Press, Vol. 1923. p. 187-209 23 p. (Methods in molecular biology (Clifton, N.J.)).
Aquaporins and Their Regulation after Spinal Cord InjuryHalsey, A. M., Conner, A. C., Bill, R. M., Logan, A. & Ahmed, Z., 18 Oct 2018, In : Stem cells. 7, 10, 174.
Biomimetic water channels: general discussion Baaden, M., Barboiu, M., Bill, R. M., Chen, C-L., Davis, J., Di Vincenzo, M., Freger, V., Fröba, M., Gale, P. A., Gong, B., Hélix-Nielsen, C., Hickey, R., Hinds, B., Hou, J-L., Hummer, G., Kumar, M., Legrand, Y-M., Lokesh, M., Mi, B., Murail, S., Pohl, P., Sansom, M., Song, Q., Song, W., Törnroth-Horsefield, S., Vashisth, H. & Vögele, M., 18 Sep 2018, In : Faraday Discussions. 209, 0, p. 205-229 25 p.
Structure and function of natural proteins for water transport: general discussion Baaden, M., Barboiu, M., Bill, R. M., Casanova, S., Chen, C-L., Conner, M., Freger, V., Gong, B., Góra, A., Hinds, B., Horner, A., Hummer, G., Kumar, M., Lokesh, M., Mitra, S., Noy, A., Pohl, P., Sadet, A., Sansom, M., Törnroth-Horsefield, S. & Vashisth, H., 14 Sep 2018, In : Faraday Discussions. 209, 0, p. 83-95 13 p.
Recombinant Membrane Protein Methods Bill, R. M., Goddard, A. D. & Rothnie, A. J., 1 Sep 2018, In : Methods. 147, p. 1-2 2 p.
Downregulation of aquaporin 3 inhibits cellular proliferation, migration and invasion in the MDA‑MB‑231 breast cancer cell line Arif, M., Kitchen, P., Conner, M., Hill, E., Nagel, D., Bill, R., Dunmore, S., Armesilla, A., Gross, S., Carmichael, A., Conner, A. & Brown, J., 21 May 2018, 16, 1, p. 713-720
Microbial expression systems for membrane proteins Dilworth, M. V., Piel, M. S., Bettaney, K. E., Ma, P., Luo, J., Sharples, D., Poyner, D. R., Gross, S. R., Moncoq, K., J. F. Henderson, P., Miroux, B. & Bill, R. M., 12 Apr 2018, In : Methods.
Transcriptome Analysis of Gene Expression Provides New Insights into the Effect of Mild Therapeutic Hypothermia on Primary Human Cortical Astrocytes Cultured under Hypoxia Salman, M. M., Kitchen, P., Woodroofe, M. N., Bill, R. M., Conner, A. C., Heath, P. R. & Conner, M. T., 14 Dec 2017, In : Frontiers in Cellular Neuroscience. 11, p. 386
Hypothermia increases aquaporin 4 (AQP4) plasma membrane abundance in human primary cortical astrocytes via a calcium/transient receptor potential vanilloid 4 (TRPV4)- and calmodulin-mediated mechanism Salman, M. M., Kitchen, P., Woodroofe, M. N., Brown, J. E., Bill, R. M., Conner, A. C. & Conner, M. T., 13 Oct 2017, In : European Journal of Neuroscience. 46, 9, p. 2542-2547 6 p.
A new panel of epitope mapped monoclonal antibodies recognising the prototypical tetraspanin CD81 Grove, J., Hu, K., Farquhar, M. J., Goodall, M., Walker, L., Jamshad, M., Drummer, H. E., Bill, R. M., Balfe, P. & McKeating, J. A., 7 Sep 2017, 2, p. 82Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy Salman, M. M., Sheilabi, M. A., Bhattacharyya, D., Kitchen, P., Conner, A. C., Bill, R. M., Woodroofe, M. N., Conner, M. T. & Princivalle, A. P., 1 Sep 2017, In : European Journal of Neuroscience. 46, 5, p. 2121-2132 12 p.
Rapid expression and purification of the hepatitis delta virus antigen using the methylotropic yeast Pichia pastoris Cartwright, S., Bill, R. M., Bui, S. T., Van, H. T. & Nguyen, H. M., 27 Jul 2017, In : BMC Research Notes. 10, 6 p., 340.
Pichia pastoris versus Saccharomyces cerevisiae: a case study on the recombinant production of human granulocyte-macrophage colony-stimulating factor Tran, A-M., Nguyen, T-T., Nguyen, C-T., Huynh-Thi, X-M., Nguyen, C-T., Trinh, M-T., Tran, L-T., Cartwright, S. P., Bill, R. M. & Tran-Van, H., 4 Apr 2017, In : BMC Research Notes. 10, 1, 8 p., 148.
Constitutively-stressed yeast strains are high-yielding for recombinant Fps1: implications for the translational regulation of an aquaporin Cartwright, S. P., Darby, R. A. J., Sarkar, D., Bonander, N., Gross, S. R., Ashe, M. P. & Bill, R. M., 9 Mar 2017, In : Microbial Cell Factories. 16, 1, 41.
Membrane protein production in the Yeast, S. cerevisiae Cartwright, S. P., Mikaliunaite, L. & Bill, R. M., 3 Aug 2016, Heterologous expression of membrane proteins. Mus-Veteau, I. (ed.). New York (US): Springer, p. 23-35 13 p. (Methods in Molecular Biology; vol. 1432).
Overcoming bottlenecks in the membrane protein structural biology pipelineHardy, D., Bill, R. M., Jawhari, A. & Rothnie, A. J., 9 Jun 2016, In : Biochemical Society Transactions. 44, 3, p. 838-844 7 p.
GPCR-styrene maleic acid lipid particles (GPCR-SMALPs): their nature and potential Wheatley, M., Charlton, J., Jamshad, M., Routledge, S. J., Bailey, S., La-Borde, P. J., Azam, M. T., Logan, R. T., Bill, R. M., Dafforn, T. R. & Poyner, D. R., 15 Apr 2016, In : Biochemical Society Transactions. 44, 2, p. 619-623 5 p.
Structural determinants of oligomerization of the aquaporin-4 channel Kitchen, P., Conner, M. T., Bill, R. M. & Conner, A. C., 25 Mar 2016, In : Journal of Biological Chemistry. 291, 13, p. 6858-6871 14 p.
The synthesis of recombinant membrane proteins in yeast for structural studiesRoutledge, S., Mikaliunaite, L., Patel, A., Clare, M., Cartwright, S. P., Bawa, Z., Wilks, M. D. B., Low, F., Hardy, D., Rothnie, A. J. & Bill, R. M., 15 Feb 2016, In : Methods. 95, p. 26-37 12 p.
Beyond water homeostasis: diverse functional roles of mammalian aquaporinsKitchen, P., Day, R. E., Salman, M. M., Conner, M. T., Bill, R. M. & Conner, A. C., Dec 2015, In : BBA - General Subjects. 1850, 12, p. 2410-2421 12 p.Plasma membrane abundance of human aquaporin 5 is dynamically regulated by multiple pathways Kitchen, P., Öberg, F., Sjöhamn, J., Hedfalk, K., Bill, R. M., Conner, A. C., Conner, M. T. & Törnroth-Horsefield, S., 16 Nov 2015, In : PLoS ONE. 10, 11, 17 p., e0143027.
Rapid tonicity induced re-localisation of endogenous aquaporin 4 in primary rat astrocytes - a therapeutic target for cytotoxic brain oedema? Day, R., Kitchen, P., Salman, M., Bill, R., Conner, A. & Conner, M., 31 Aug 2015, 63, Suppl.S1, p. E406-E407 2 p., T13-01B.
Identification and molecular mechanisms of the rapid tonicity-induced relocalization of the aquaporin 4 channel Kitchen, P., Day, R. E., Taylor, L. H. J., Salman, M. M., Bill, R. M., Conner, M. T. & Conner, A. C., 3 Jul 2015, In : Journal of Biological Chemistry. 290, p. 16873-16881 9 p.
Structural basis for receptor activity-modifying protein-dependent selective peptide recognition by a G protein-coupled receptor Booe, JM., Walker, C. S., Barwell, J., Kuteyi, G., Simms, J., Jamaluddin, MA., Warner, ML., Bill, R. M., Harris, PW., Brimble, MA., Poyner, D. R., Hay, D. L. & Pioszak, AA., 18 Jun 2015, In : Molecular Cell. 58, 6, p. 1040-1052 13 p.
Editorial overview: new protein production tools for structural biology Berger, I. & Bill, R. M., Jun 2015, In : Current Opinion in Structural Biology. 32, p. v–vii 3 p.
Hijacked then lost in translation: the plight of the recombinant host cell in membrane protein structural biology projects Bill, R. M. & von der Haar, T., Jun 2015, In : Current Opinion in Structural Biology. 32, p. 147-155 9 p.
Pichia pastoris regulates its gene-specific response to different carbon sources at the transcriptional, rather than the translational, level Prielhofer, R., Cartwright, S., Graf, A. B., Valli, M., Bill, R., Mattanovich, D. & Gasser, B., 11 Mar 2015, In : BMC Genomics. 16, 1, 17 p., 167.
G-protein-coupled receptor solubilization and purification for biophysical analysis and functional studies, in the total absence of detergent Jamshad, M., Charlton, J., Lin, Y-P., Routledge, S. J., Bawa, Z., Knowles, T. J., Overduin, M., Dekker, N., Dafforn, T. R., Bill, R. M., Poyner, D. R. & Wheatley, M., 27 Feb 2015, In : Bioscience Reports. 35, 2, 10 p., e00188.
Recombinant protein subunit vaccine synthesis in microbes: a role for yeast? Bill, R. M., 2015, In : Journal of Pharmacy and Pharmacology. 67, 3, p. 319-328 10 p.
Functional recombinant protein is present in the pre-induction phases of Pichia pastoris cultures when grown in bioreactors, but not shake-flasks Bawa, Z., Routledge, S. J., Jamshad, M., Clare, M., Sarkar, D., Dickerson, I., Ganzlin, M., Poyner, D. R. & Bill, R. M., 4 Sep 2014, In : Microbial Cell Factories. 13, 1, 13 p., 127.Contribution to journal › ArticleHuman aquaporins: regulators of transcellular water flow Day, R. E., Kitchen, P., Owen, D., Bland, C., Marshall, L., Conner, A. C., Bill, R. M. & Conner, M. T., 1 May 2014, In : BBA - General Subjects.
Playing catch-up with Escherichia coli: using yeast to increase success rates in recombinant protein production experiments Bill, R. M., 5 Mar 2014, In : Frontiers in Microbiology. 5, 5 p., 85.
Antifoams: the overlooked additive? Routledge, S. J., Poyner, D. R. & Bill, R. M., 2014, In : Pharmaceutical Bioprocessing. 2, 2, p. 103-106 4 p.
Production, purification and characterization of recombinant, full-length human claudin-1 Bonander, N., Jamshad, M., Oberthür, D., Clare, M., Barwell, J., Hu, K., Farquhar, M. J., Stamataki, Z., Harris, H. J., Dierks, K., Dafforn, T. R., Betzel, C., McKeating, J. A. & Bill, R. M., 21 May 2013, In : PLoS ONE. 8, 5, 12 p., e64517.
Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential? Hipkiss, A. R., Cartwright, S. P., Bromley, C., Gross, S. R. & Bill, R. M., 25 Feb 2013, In : Chemistry Central Journal. 7, 1, 38.
An emerging consensus on aquaporin translocation as a regulatory mechanismConner, A. C., Bill, R. M. & Conner, M. T., Feb 2013, In : Molecular Membrane Biology. 30, 1, p. 101-112 12 p.
Foreword for EDICT Special Edition, volume 2 Bill, R. M. & Byrne, B., 23 Jan 2013, In : Molecular Membrane Biology. 30, 2, p. 113 1 p.
Introduction to EDICT volume 1 Bill, R. M. & Byrne, B., 19 Nov 2012, In : Molecular Membrane Biology. 30, 1, p. 2 1 p.
L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner Cartwright, S. P., Bill, R. M. & Hipkiss, A. R., 12 Sep 2012, In : PLoS ONE. 7, 9, 7 p., e45006.
The effect of antifoam addition on protein production yields Routledge, S. J. & Bill, R. M., 23 Apr 2012, Recombinant protein production in yeast: methods and protocols. Bill, R. M. (ed.). Humana Press, p. 87-97 11 p. (Methods in molecular biology; vol. 866)(Springer protocols).
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