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Durham University

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Staff Profile

Professor Martin Cann

Professor in the Department of Biosciences
Telephone: +44 (0) 191 33 43985
Fax: (+44) 191 334 1201
Visiting Professor in the Department of Chemistry

Contact Professor Martin Cann (email at m.j.cann@durham.ac.uk)

My laboratory is interested in a variety of signal transduction mechanisms mediated by nucleotides. We are based within the Department of Chemistry and work closely with physicists, chemists, and mathematicians on a number of research questions.

1. Carbon dioxide sensing. CO2 is a critical constituent of all known biological systems yet its molecular interactions with the cell are relatively unexplored. Cells are exposed to fluctuating CO2 through altered environmental conditions, changes in cell metabolism, and the effects of lifestyle and pathology. Our current work is directed toward understanding how CO2 impacts on cell function through alterations in cellular levels of the second messenger molecule, cAMP.

2. Resistance protein function. Plant resistance proteins trigger disease resistance in response to pathogen (avirulence) proteins. R-proteins typically consist of a nucleotide binding (NB) domain adjacent to one or more ARC domains and a Leucine Rich Repeat (LRR). The LRR is involved in pathogen sensing and is thought to transmit this signal, via the ARC domains, to the NB domain. The role of the NB domain is uncertain but is presumed to specify an ATPase. My laboratory is developing methodology for the expression of recombinant proteins corresponding to the key signalling domains of R-proteins and using these proteins to investigate the biochemistry of these key molecules of the plant immune system. This work is performed in collaboration with Dr Lars-Olof Palsson (Chemistry, BSI) and Dr Gary Sharples (SBBS, BSI) and is supported by the BBSRC.

3. Protein dynamics. We are interested in how protein thermal motion can contribute to function. In particular, we are investigating dynamics contributes to allostery in the Catabolite Activated Protein (CAP) of Escherichia coli. We using a combination of coarse grained modelling, atomic simulations, biochemistry, and structural biology to achieve these aims. This work is performed in collaboration with Prof Tom McLeish (Physics, BSI), Prof Mark Wilson (Chemistry, BSI), and Dr Ehmke Pohl (SBBS/Chemistry, BSI).

 

Research Groups

Department of Biosciences

Research Interests

  • Cell biology of bicarbonate and carbon dioxide
  • Cyclic nucleotide signaling
  • Signal transduction

Teaching Areas

  • Level 1 Molecular Basis of Life (6 hours/year.)
  • Level 2 Animal Physiology (13 hours/year.)
  • Level 2 Clinical and Metabolic Biochemistry (23 hours/year.)
  • Level 3 Stress and Responses to the Environment (10 hours/year.)

Publications

Authored book

  • Townsend, PD, Rodgers, TL, Pohl, E, Wilson, MR, Cann, MJ & McLeish, T C B (2015). Physical Biology of Proteins and Peptides. Springer.

Chapter in book

  • Holmes AP, Nunes AR, Cann MJ, & Kumar P (2015). Ecto-5'-Nucleotidase, Adenosine and Transmembrane Adenylyl Cyclase Signalling Regulate Basal Carotid Body Chemoafferent Outflow and Establish the Sensitivity to Hypercapnia. In Arterial Chemoreceptors in Physiology and Pathophysiology. 860: 279-289.

Journal Article

  • Slootweg, Erik J., Spiridon, Laurentiu N., Martin, Eliza C., Tameling, Wladimir I.L., Townsend, Philip D., Pomp, Rikus, Roosien, Jan, Drawska, Olga, Sukarta, Octavina C.A., Schots, Arjen, Borst, Jan Willem, Joosten, Matthieu H.A.J., Bakker, Jaap, Smant, Geert, Cann, Martin J., Petrescu, Andrei-Jose & Goverse, Aska (2018). Distinct Roles of Non-Overlapping Surface Regions of the Coiled-Coil Domain in the Potato Immune Receptor Rx1. Plant Physiology 178(3): 1310-1331.
  • Linthwaite, V.L., Janus, J.M., Brown, A.P., Wong-Pascua, D., O’Donoghue, A.C., Porter, A., Treumann, A., Hodgson, D.R.W. & Cann, M.J. (2018). The identification of carbon dioxide mediated protein post-translational modifications. Nature Communications 9: 3092.
  • Townsend, P.D., Dixon, C.H., Slootweg, E.S., Sukarta O.C.A., Yang, A.W.H., Hughes, T.R., Sharples, G.J., Palsson, L.-O., Takken, F.L.W., Goverse, A. & Cann, M.J. (2018). The intracellular immune receptor Rx1 regulates the DNA-binding activity of a Golden2-like transcription factor. The Journal of Biological Chemistry 293(9): 3218-3233.
  • Turner, M.J., Saint-Crib, V., Patel, W., Ibrahim, S.H., Verdon, B., Ward, C., Garnett, J.P., Tarran, R., Cann, M.J. & Gray, M.A. (2016). Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator-dependent anion and fluid secretion in airway epithelia. The Journal of Physiology 594(6): 1643-1661.
  • Fenyk, S., Dixon, C.H., Kittens, W.H., Townsend, P.D., Sharpies, G.J., Pålsson, L.-O., Takken, F.L.W. & Cann, M.J. (2016). The tomato Nucleotide-Binding Leucine-Rich Repeat (NLR) Immune Receptor I-2 couples DNA-Binding to Nucleotide-Binding Domain Nucleotide Exchange. Journal of Biological Chemistry 291(3): 1137-1147.
  • McLeish, T.C.B., Cann, M.J. & Rodgers, T.L. (2015). Dynamic Transmission of Protein Allostery without Structural Change: Spatial Pathways or Global Modes? Biophysical Journal 109(6): 1240-1250.
  • Townsend, P.D., Rogers, T.L., Pohl, E., Wilson, M.R., McLeish, T.C.B. & Cann, M.J. (2015). Global low-frequency motions in protein allostery: CAP as a model system. Biophysical Reviews 7(2): 175-182.
  • Fenyk, Stepan, Townsend, Philip D., Dixon, Christopher H., Spies, Gerhard B., de San Eustaquio Campillo, Alba, Slootweg, Erik J., Westerhof, Lotte B., Gawehns, Fleur K.K., Knight, Marc R., Sharples, Gary J., Goverse, Aska, Pålsson, Lars-Olof, Takken, Frank L.W. & Cann, Martin J. (2015). The Potato Nucleotide-Binding Leucine-Rich Repeat (NLR) Immune Receptor Rx1 is a Pathogen Dependent DNA-Deforming Protein. Journal of Biological Chemistry 290(41): 24945-24960.
  • Townsend, P.D., Rodgers, T.L., Glover, L.C., Korhonen, H.J., Richards, S.A., Colwell, L.J., Pohl, E., Wilson, M.R., Hodgson, D.R.W., McLeish, T.C.B. & Cann, M.J. (2015). The role of protein-ligand contacts in allosteric regulation of the Escherichia coli Catabolite Activator Protein. Journal of Biological Chemistry 290(36): 22225-22235.
  • Townsend, P., Jungwirth, B., Pojer, P., Bußmann, M., Money, V.A., Cole, S.T., Pühler, A., Tauch, A., Bott, M., Cann, M.J. & Pohl, E. (2014). The crystal structures of apo and cAMP-bound GlxR from Corynebacterium glutamicum reveal structural and dynamic changes upon cAMP binding in CRP/FNR family transcription factors. PlosONE 9(12): e113265.
  • Meigh, L., Greenhalgh, S.A., Rodgers, T.L., Cann, M.J., Roper, D.I. & Dale, N. (2013). CO2 directly modulates connexin 26 by formation of carbamate bridges between subunits. eLife 2: e01213.
  • Rodgers, TL, Townsend, PD, Burnell, D, Jones, ML, Richards, SA, McLeish, TCB, Pohl, E, Wilson, MR & Cann, MJ (2013). Modulation of Global Low-Frequency Motions Underlies Allosteric Regulation: Demonstration in CRP/FNR Family Transcription Factors. PLoS Biology 11(9): e1001651.
  • Fenyk, S, de San Eustaquio Campillo, A, Pohl, E, Hussey, PJ & Cann, MJ (2012). A Nucleotide Phosphatase Activity in the Nucleotide Binding Domain of an Orphan Resistance Protein from Rice. The Journal of Biological Chemistry 287(6): 4023-4032.
  • Topal, H, Fulcher, NB, Bitterman, J, Salazar, E, Buck, J, Levin, LR, Cann, MJ, Wolfgang, MC & Steegborn, C (2012). Crystal Structure and Regulation Mechanisms of the CyaB Adenylyl Cyclase from the Human Pathogen Pseudomonas aeruginosa. Journal of Molecular Biology 416(2): 271-286.
  • Cook, Z.C., Gray, M.A. & Cann, M.J. (2012). Elevated Carbon Dioxide Blunts Mammalian cAMP Signaling Dependent on Inositol 1,4,5-Triphosphate Receptor-mediated Ca2+ Release. Journal of Biological Chemistry 287(31): 26291-26301.
  • Fulcher, NB, Holliday, PM, Klem, E, Cann, MJ & Wolfgang, MC (2010). The Pseudomonas aeruginosa Chp chemosensory system regulates intracellular cAMP levels by modulating adenylate cyclase activity. Molecular Microbiology 76(4): 889-904.
  • Townsend, PD, Holliday, PM, Fenyk, S, Hess, KC, Gray, MA, Hodgson, DRW & Cann, MJ (2009). Stimulation of Mammalian G-protein-responsive Adenylyl Cyclases by Carbon Dioxide. Journal Of Biological Chemistry 284(2): 784-791.
  • Cann, M (2007). A subset of GAF domains are evolutionarily conserved sodium sensors. Molecular Microbiology 64(2): 461-472.
  • Cann, M.J. (2007). Sodium regulation of GAF domain function. Biochemical Society Transactions 35(5): 1032-1034.
  • Williamson, D., Cann, M.J. & Hodgson, D.R.W. (2007). Synthesis of 5'-Amino-5'-deoxyguanosine-5'-N-phosphoramidate and its Enzymatic Incorporation at the 5'-Termini of RNA Molecules. Chemical Communications 2007(47): 5096-5098.
  • J.H. Yu, D. Parker, R. Pal, R.A. Poole & M.J. Cann (2006). A europium complex that selectively stains nucleoli of cells. Journal of the American Chemical Society 128(7): 2294-2299.
  • Hammer, A., Hodgson, D.R.W. & Cann, M.J. (2006). Regulation of prokaryotic adenylyl cyclases by CO₂. Biochemical Journal 396(2): 215-218.
  • R. A. Poole, G. Bobba, M. J. Cann, J. C. Frias, D. Parker & R. D. Peacock (2005). Synthesis and characterisation of highly emissive and kinetically stable lanthanide complexes suitable for usage 'in cellulo'. Organic & Biomolecular Chemistry 3(6): 1013-1024.
  • Cann, M.J. (2004). Bicarbonate stimulated adenylyl cyclases. IUBMB Life 56(9): 529-534.
  • Y. Bretonniere, M. J. Cann, D. Parker & R. Slater (2004). Design, synthesis and evaluation of ratiometric probes for hydrogencarbonate based on europium emission. Organic & Biomolecular Chemistry 2(11): 1624-1632.
  • Cann, M.J. (2004). Signalling through cyclic nucleotide monophosphates in cyanobacteria. New Phytologist 161(23-34).
  • Cann, M.J., Hammer, A., Zhou, J. & Kanacher, T. (2003). A defined subset of adenylyl cyclases is regulated by bicarbonate ion. Journal of Biological Chemistry 278(37): 35033-35038.
  • J. C. Frias, G. Bobba, M. J. Cann, C. J. Hutchison & D. Parker (2003). Luminescent nonacoordinate cationic lanthanide complexes as potential cellular imaging and reactive probes. Organic and Biomolecular Chemistry 1(6): 905-907.
  • M.J. Cann (2003). Signalling through cyclic nucleotide monophosphates in cyanobacteria. New Phytologist 161: 23-34.
  • M.J. Cann & L.R. Levin (2002). Identification of transmembrane adenylyl cyclase isoforms. Methods Enzymol 345: 150-9.
  • Bretonnière, Y., Cann, M.J., Parker, D. & Slater, R. (2002). Ratiometric probes for hydrogencarbonate analysis in intracellular or extracellular environments using europium luminescence. Chemical Communications 2002(17): 1930-1931.
  • Cann, M.J., Chung, E. & Levin, L.R. (2000). A new family of adenylyl cyclase genes in the male germline of Drosophila melanogaster. Development Genes and Evolution 210(4): 200-206.
  • Cann, M.J. & Levin, L.R. (2000). Restricted expression of a truncated adenylyl cyclase in the cephalic furrow of Drosophila melanogaster. Development Genes and Evolution 210(1): 34-40.
  • Chen, Y., Cann, M.J., Litvin, T.N., Iourgenko, V., Sinclair, M.L., Levin, L.R. & Buck, J. (2000). Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor. Science 289(5479): 625-628.
  • Buck, J., Sinclair, M.L., Schapal, L., Cann, M.J. & Levin, L.R. (1999). Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals. Proceedings of the National Academy of Sciences 96(1): 79-84.
  • Cann, M.J. & Levin, L.R. (1998). Genetic characterization of adenylyl cyclase function. Advances in Second Messenger and Phosphoprotein Research 32: 121-135.
  • Iourgenko, V., Kliot, B., Cann, M.J. & Levin, L.R. (1997). Cloning and characterization of a Drosophila adenylyl cyclase homologous to mammalian type IX. FEBS Letters 413(11): 104-108.

Supervises