Bonnie Ann Wallace

Professor of Molecular Biophysics
Department of Crystallography
Institute of Structural and Molecular Biology
Birkbeck College
University of London
London WC1E 7HX U.K.

phone: 44-(0)207-631-6800
fax: 44-(0)207-631-6803
email: ubcg25a@mail.cryst.bbk.ac.uk

Ph.D. (Molecular Biophysics and Biochemistry) Yale University
Jane Coffin Childs Postdoctoral Fellow, Harvard University
Jane Coffin Childs Postdoctoral Fellow, MRC-LMB, Cambridge
Fellow, AAAS; Fellow, Institute of Biology; Fellow, Royal Society of Chemistry; Fellow, IUPAC
2009 Royal Society of Chemistry Interdisciplinary Prize
2010 AstraZeneca Award from the Biochemical Society

Book on CD and SRCD:

"Modern Techniques for Circular Dichroism and Synchrotron Radiation Circular Dichroism Spectroscopy"

B.A. Wallace and R.W. Janes, Editors
click here for information on contents and how to order

 

 

New PhD studentship available on “Structure and Function of Voltage-Gated Sodium Channels” (starting academic year 2014-2015)


 

My lab focuses on structure/function studies of membrane proteins and polypeptides, especially those involved in ion translocation and transport. Of particular interest are voltage-gated sodium channels: we have recently determined the first crystal structure of a sodium channel in its open conformation . We have also determined the first crystal structures of complex of a sodium channel with several eukaryotic sodium channel blockers, which we have shown (in collaboration with the Clapham Lab at Harvard) block prokaryotic channels, making this channel an excellent candidate for drug discovery/development.  In the past we have determined the crystal structures of the polypeptide ion channels such as antiamoebin , and trichtoxin (polypeptide antibiotics that act as ion channels). We have also developed a new chimeric approach for expression of membrane proteins, and have produced a functional "minimal" sodium channel pore .

My lab uses the techniques of X-ray crystallography and circular dichroism spectroscopy, cloning and expression, bioinformatics, and molecular modelling, as well as functional studies to examine structure/function relationships for ion channels.

Methodologically, we develop techniques and applications for synchrotron radiation circular dichroism (SRCD)spectroscopy of proteins, especially for its use in Structural and Functional Genomics, and for circular dichroism spectroscopy of membrane proteins, including ways of mitigating solvent shifts, differential scattering, and absorption flattening effects. We have created the DICHROWEB website for secondary structural calculations , new soluble and membrane protein reference databases for CD analyses, a CD data processing and archive package "CDtool" for use with conventional CD and SRCD beamline data.

In a collaborative project with R.W. Janes of Queen Mary, University of London, we have created the Protein Circular Dichroism Data Bank (PCDDB), a deposition and archiving data bank and associated validation software for circular dichroism spectra and the DichroMatch method for structural analyses.

Selected Publications:

[journal cover]

·         McCusker, E.C., D'Avanzo, N., Nichols, C.G., and Wallace, B.A. (2011) Simplified Bacterial "Pore" Provides Insight into the Assembly, Stability and Structure of Sodium Channels. J. Biol. Chem. 286:16386-16391.

·         McCusker, E.C., Bagneris, C., Naylor, C.E., Cole, A.R., D'Avanzo, N., Nichols, C.G., and Wallace, B.A. (2012) Structure of a Bacterial Voltage-Gated Sodium Channel Pore Reveals Mechanisms of Opening and Closing. Nature Communications 3:1102.

·         O'Reilly, A.O., Eberhardt, E., Weidner, C., Alzheimer, C., Wallace, B.A., Lampert, A. 2012. Bisphenol A binds to the local anesthetic receptor site to block the human cardiac sodium channel. PLOS One 7:e41667

·         Erdmanis, L., O’Reilly, A.O., Williamson, M.S., Field, L.M., Turberg, A., and Wallace, B.A. (2012) Association of Neonicotinoid Insensitivity with a Conserved Residue in the Loop D Binding Region of the Tick Nicotinic Acetylcholine Receptor. Biochemistry 51: 4627-4629.

·         Powl, A.M., Miles, A.M., and Wallace, B.A. (2012) Transmembrane and extramembrane contributions to membrane protein thermal stability: studies with the nachbac sodium channel. Biochim. Biophys. Acta (Biomembranes) 1818:889-895. doi:10.1016/j.bbamem.2011.12.019.

·         Klose, D., Wallace, B.A., and Janes, R.W. (2012) DichroMatch: A website for similarity searching of circular dichroism spectra. Nucleic Acids Res. 40:547-552.

·         Janes, R.W., Miles, A.J., Woollett, B., Whitmore, L., Klose, D., and Wallace, B.A. (2012) Circular Dichroism Spectral Data and Metadata in the Protein Circular Dichroism Data Bank (PCDDB): A Tutorial Guide to Accession and Deposition. Chirality 24: 751-63.

·         Woollett, B., Klose, D., Cammack, R., Janes, R.W., and Wallace, B.A. (2012) JCAMP-DX for circular dichroism spectra and metadata. Pure and Applied Chemistry 84: 2171-2182.

·         Ulmschneider, M.B., Bagneris, C., McCusker, E.C., DeCaen, P.G., Delling, M., Clapham, D.E., Ulmschneider, J.P. and Wallace, B.A. (2013) Molecular dynamics of ion transport through the open conformation of a bacterial voltage-gated sodium channel. Proc. Nat. Acad. Sci. USA 110, 6364-6369.

·         D'Avanzo, N., McCusker, E.C., Powl, A.M., Miles, A.J., Nichols, C.G., and Wallace, B.A. (2013) Differential Lipid Dependence of the Function of Bacterial Sodium Channels. PLOSone 8: e61216.

·         Lopes, J.L.S., Orcia, D., Araujo, A.P.U., DeMarco, R., and Wallace, B.A.(2013) Folding factors and partners for the intrinsically disordered protein micro-exon gene 14 (MEG-14). Biophysical Journal 104:2512-2520.

·         Fernandez, D. I., Sani, M.–A., Miles, A. J, Wallace, B A, and Separovic, F. (2013) Membrane defects enhance the interaction of antimicrobial peptides, aurein 1.2 versus caerin 1.1. Biochimica et Biophysica Acta 1828: 1863–1872.

·         Woollett, B., Whitmore, L., Janes, R.W., and Wallace, B.A. (2013) ValiDichro: a website for validating and quality control of protein circular dichroism spectra. Nucleic Acids Research 41:W417-421.

·         Miles, A.J, Fedosova, N.U, Hoffmann, S.V., Wallace, B.A., Esmann, M. (2013) Stabilisation of Na,K-ATPase structure by the cardiotonic steroid ouabain. BBRC 435:300-305.

·         Bagneris, C., DeCaen, P.G., Hall, B.A., Naylor, C.E., Clapham, D.E., Kay, C.W.M., Wallace, B.A. (2013) Role of the C-terminal domain in the structure and function of tetrameric sodium channels, Nature Communications 4:2645.

·         O’Reilly, A.O., Cole, A.R., Lopes, J.L.S., Lampert, A., Wallace, B.A. (2013) Chaperone-mediated native folding of a B-scorpion Toxin in the periplasm of Escherichia coli. BBA (General Subjects) 1840:10-15.

·         Assuero F. Garcia; Jose L.S. Lopes; Antonio J. Costa-Filho; B. A. Wallace, Ana P.U. Araujo. (2013) Membrane Interactions of Calgranulin C (S100A12). PLOSone 8:e82555.

·         Kalsi, S. Powl, A.M. Wallace, B.A., Morgan, H., de Planque, M.R.R. (2014) Shaped apertures in photoresist films enhance the lifetime and mechanical stability of suspended lipid bilayers.  Biophysical J 106:1650-1659.  

·         Bagneris, C., DeCaen, P.G., Naylor, C.E., Pryde, D., Nobeli, I., Clapham, D.E., & Wallace, B.A. (2014) The Prokaryotic NavMs Channel as a Structural and Functional Model for Eukaryotic Sodium Channel Antagonism. Proc. Natl. Acad. Sci. USA 111:.8428-8433.


 

Our work is and has been supported by grants from the BBSRC, the EPSRC, the MRC and the Wellcome Trust.


In collaboration with Dr. Alison Rodger of Warwick University, we organise the EU/UK Annual CD Summer School. This year it will be held on 7-9 June 2014. Details of the associated UK/EU Annual CD meeting can be accessed here.

 

Current Group Members

 

Postdocs:  Dr. Lee Whitmore, Dr. Andrew Miles, Dr. Claire Bagneris, Dr. Claire Naylor, Dr. Juliana Yoneda

PhD Students:  Wayne Miller, Alex Henderson, Elliot Drew, Matthew Colledge

Shared PhD Students:  Chris Penny (UCL), Manoli Kavishwar (RVC), Tomasz Kosciolek (UCL)