Dr Mark Howard
- Contact details
The University of Western Australia (M310)
35 Stirling Highway
CRAWLEY WA 6009
- +61 8 6488 4485
- Room 1.07, Bayliss Building, Perth campus
- Mark has a BSc and a PhD Chemistry from The University of Aston where he studied from 1988-1994. He moved to take up a post-doctoral position at Cambridge University with Prof. Richard Perham FRS, where he moved into biological NMR, before becoming Facility Technical Officer at The University of Kent in 1997. He became NMR Facility Manager at the Medical Research Councul Centre for Protein engineering (MRC CPE) at Cambridge, under the directorship of Prof. Sir Alan Fersht FRS before taking a brief spell in industry working on the NMR method development of DNP Hypersense for metabolism applications. Mark returned to Kent as NMR Facility Manager in 2001 and was promoted to academic status in 2005 and gained a postgraduate certificate in higher education (PGCHE) from Kent. He stayed at Kent for 15 years before moving to UWA in May 2016.
- Key research
- NMR studies of molecular interactions including protein-ligand, protein-protein and pharmaceutical drug discovery.
- Pharmaceutical and biopharmaceutical quality control using NMR spectroscopy.
- NMR-based metabolism, metabolomics and biological profiling.
- Multidimensional NMR structure and function studies of proteins, peptides and natural products.
- BOOK CHAPTERS
M.L.Rowe, J.L.Wagstaff and M. J. Howard. (2014) NMR in Ligand Binding Studies. Modern NMR Techniques for Synthetic Chemistry, Pp 63-124. Ed. J. Fisher, CRC Press.
M. J. Howard. (2005) Sample Preparation Procedures for High-Resolution Nuclear Magnetic resonance Studies of Aqueous and Stabilized Solutions of Therapeutic Peptides. Therapeutic Proteins: Methods and Protocols, Humana Press.
J. Homer, S.U. Patel, and M.J. Howard. (1992) NMR Spectroscopy with Ultrasound, Current Trends in Sonochemistry, pp 136 - 147, ed. G.J. Price, Royal Society of Chemistry
SELECTED RECENT PAPERS
K.L.Richards, M.L.Rowe, P.B.Hudson, R.A.Williamson and M.J.Howard (2016). Combined ligand-observe 19F and protein-observe 15N,1H-HSQC NMR suggests phenylalanine as the key Δ-somatostatin residue recognized by human protein disulfide isomerase Sci. Rep. 5, 19518; doi: 10.1038/srep19518.
J.L.Sorge, J.L.Wagstaff, M.L.Rowe, R.A.Williamson, and M.J.Howard. (2015). Q2DSTD NMR deciphers epitope-mapping variability for peptide recognition of integrin αvβ6. Org. Biomol Chem. 13, 8001-7.
S.Blanchet, M.Rowe, T.von der Haar, C.Fabret, S.Demais, M.J.Howard* and O.Namy*. (2015). New insights into stop codon recognition by eRF1. Nucleic Acids Res. 43, 3298-3308.
R.Curtis-Marof, D.Doko, M.L.Rowe, K.L.Richards, R.A.Williamson and M.J.Howard. (2014). 19F NMR spectroscopy monitors ligand binding to recombinantly fluorine-labelled b’x from human protein disulphide isomerase (hPDI). Org. Biomol. Chem., 2014, 12 (23), 3808 – 3812.
A.D.Lawrence, S.Frank, S.Newnham, M.Lee, I.Brown, W.Xue, M.L.Rowe, D.P.Mulvihill, M.Prentice, M.J.Howard* and M.J. Warren* (2014). Solution structure of a bacterial microcompartment targeting peptide and its application in the construction of an ethanol bioreactor. ACS Synth. Biol. 3(7):454-65.
N.Ley, M.Rowe, R.A.Williamson and M.J.Howard. (2014). Optimising selective excitation pulses to maximise saturation transfer difference NMR spectroscopy. RSC Adv. 4, 7347.
A.G.Irvine, A.K.Wallis, N.Sanghera, M.L.Rowe, L.W.Ruddock, M.J.Howard, R.A.Williamson, C.A.Blindauer and R.B. Freedman. (2014). Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway. PLoS One 9, e82511.
J.L.Wagstaff, R.J.Masterton, J.F.Povey, C.M.Smales*, M.J.Howard* (2013). 1H NMR Spectroscopy Profiling of Metabolic Reprogramming of Chinese Hamster Ovary Cells upon a Temperature Shift during Culture. PLoS One 8, e77195.
Y.K.S.Man, D.DiCara, N.Chan, S.Vessillier, S.J.Mather, M.L.Rowe, M.J.Howard, J.F.Marshall and A.Nissim (2013). Structural guided scaffold phage display libraries as a source of bio-therapeutics. PLoS One, 8, e70452.
S.L.Taylor, H.Crawley-Snowdon, J.L.Wagstaff, M.L.Rowe, M.Shepherd, R.A.Williamson and M.J.Howard (2013). Measuring protein reduction potentials using 15N HSQC NMR Spectroscopy. Chem. Commun., 49, 1847-1849.
N.T. Amin, A.K. Wallis, S.A. Wells, M.L. Rowe, R.A. Williamson, M.J. Howard* and R.B. Freedman* (2013). High-resolution NMR studies of structure and dynamics of human ERp27 indicate extensive inter-domain flexibility. Biochem. J. 450, 321-331.
J.L.Wagstaff, M.L.Rowe, S.Hsieh, D.DiCara, J.F.Marshall, R.A.Williamson and M.J.Howard. (2012) 15N NMR relaxation and structural elucidation of peptides in the presence and absence of trifluoroethanol illuminates the critical molecular nature of integrin αvβ6 ligand specificity. RSC Adv., 2, 11019-11028.
J.L. Wagstaff, S. Vallath, J.F. Marshall, R. A. Williamson* and M.J. Howard* (2010). Two-dimensional heteronuclear saturation transfer difference NMR reveals detailed integrin αvβ6 protein-peptide interactions. Chem. Commun. 46, 7533-7535.
M.L. Rowe, L.W. Ruddock, G. Kelly, J.M.Schmidt, R.A. Williamson* and M.J. Howard* (2009). Solution Structure and Dynamics of ERp18: a Small ER Resident Oxidoreductase. Biochemistry, 48, 4596-4606.
- Roles, responsibilities and expertise
- Mark is the Academic Lead of the CMCA NMR Facility housed in the School of Chemistry and Biochemistry and UWA where he uses NMR method development to answer specific questions.
He has over 25 years of expertise in NMR spectroscopy that has included proteins, peptides, natural products and metabolomics. He has solved several structures of proteins and studied protein-ligand interactions using ligand-observe and protein observe methods using 1H, 13C, 15N, 31P and 19F NMR. Ligand-observe approaches are of special interest in the field of pharmaceutical drug discovery.
Mark also uses NMR spectroscopy to study dynamic processes in molecules in solution and has extensive experience in measuring nuclear relaxation properties and applying such data to timescales and exchange phenomena.
His is also developing applications of 19F NMR as a specific probe for both biology and chemistry. He has developed 19F NMR to monitor protein-ligand binding and physical properties using fluorinated species.
Mark is keen to use NMR spectroscopy to answer new scientific questions and promotes utility of this technique; please contact him if you think NMR can help your research project or technical questions.
- Chartered Scientist
Member of the Royal Society of Chemistry
- Current projects
- 1.Enhancing ligand-observe NMR spectroscopy for pharmaceutical drug discovery and protein-ligand interactions. The main thrust is the development of quantitative NMR approaches to increase efficiency in the drug-discovery pipeline.
2.Using NMR spectroscopy as a quality control tool in pharmaceutical product analysis. Liquid and solid-state NMR spectroscopy provides excellent tools to study pharmaceutical formulations and probe the effects of preparation and storage of drugs prior to dispensing and use.
3.This research involves the development and application of NMR in metabolism and metabolomics research. Our interests cover a wide variety of projects with medical, biological, ecological and consumer applications to identify markers that flag important changes. For example, changes due to disease, nutrients, environment or batch production.
4.NMR and biophysical characterisation of thioredoxin (Trx) proteins involved as disulphide bond catalysis and protein-folding chaperones in the endoplasmic reticulum (ER). Protein folding in the ER is of great interest in fundamental biochemistry as well as the biopharmaceutical industry as it directly correlates to antibody drug production. Structure-function studies of Trx proteins using protein-ligand interactions, 19F biological NMR, dynamic NMR and other approaches in order to understand the molecular bases of ER protein operation.
- Research profile
Research profile and publications