Associate Professor Boris Martinac
Associate Professor
Molecular Biophysics
P harmacology Unit M510
School of Medicine and Pharmacology
QEII Medical Centre
The University of Western Australia
Crawley , WA 6009, Australia

Personal Website Address: http://www.pharm.uwa.edu.au/aussie/research/biophys/biophys.html
Email : bmartinac@receptor.pharm.uwa.edu.au

Research Aims

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The Big Question

• Molecular basis of mechanotransduction in living cells.

The Short-term goals

• Biophysics, molecular biology and pharmacology of prokaryotic - bacterial and archaeal - mechanosensitive (MS) ion channels.
• Biophysics and molecular biology of bacterial porins.

Group (lab) Members and areas of research

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Dr Christel Norman, Postdoctoral Research Associate
(Molecular biology of prokaryotic MS channels)

Dr Zhen-Wei Liu, Postdoctoral Research Associate
(Electrophysiology of prokaryotic MS channels)

Mr Albert Raso, Graduate Research Assistant
(In vivo studies in bacteria)

Thom Nguyen, PhD student
(Pharmacology of bacterial MS channels)

Grischa R Meyer, PhD student
(Molecular dynamics simulations and molecular modelling in prokaryotic MS channels)

John Rayment, PhD student
(Site-directed mutagenesis and electronparamagnetic (EPR) resonance spectroscopy of bacterial MS channels)

I-Jung Tsai, Laboratory Assistant
(Site-directed mutagenesis and EPR spectroscopy of bacterial MS channels)

Funding

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Current

1. ARC Discovery Project (2003-2005): "Early evolutionary origins of mechanosensory transduction: structure, function and phylogenetic studies of the family of mechanosensitive channels in cell-walled organisms".
2. ARC Discovery Project (2004-2006): "The role of mechanosensitive (MS) channels in magnetoreception".

Applications submitted or planned

1. NH&MRC Project Grant: "Bacterial mechanosensitive channels as novel targets for antibacterial agents."

Techniques in the Laboratory

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Besides molecular-biological methods and electrophysiological patch-clamp and planar bilayer techniques presently used in the laboratory, also electron-crystallography, as well as computer and mathematical modeling have successfully been employed through the expertise provided by several overseas (USA and Europe) laboratories with which the laboratory has established close collaboration.

Employing electron paramagnetic resonance (EPR) technique has recently expanded the current multidisciplinary approach in structure and function studies of MS ion channels.  

Currently active

Site-directed mutagenesis, PCR, gene cloning, gel and column chromatography, patch-clamp recording, planar bilayer recording, EPR spectroscopy (in collaboration with Department of Molecular Physiology and Biological Physics, University of Virginia, USA and Chemistry Unit, School of Biomedical and Chemical Sciences, UWA), molecular dynamics simulations (in collaboration with the Beckman Institute, University of Illinois at Urbana-Champaign, USA).

In development

Green fluorescent protein (GFP) labelling technique

Main areas of expertise

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Top three areas of knowledge

1. Structure and function of ion channels
2. Membrane biophysics
3. Biophysics and physiology of mechanotransduction

Top three technical skills

1. Patch-clamp recording
2. Planar bilayer recording
3. EPR spectroscopy

A statement on your most significant contributions to this research field

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A/Prof Boris Martinac has co-pioneered characterisation of ion channels in several microorganisms (ciliated protozoa, yeast, bacteria and archaea) by applying electrophysiology to microbial cells. The discovery of mechanosensitive (MS) ion channels in bacteria presents his major original contribution to the ion channel research field has been. Dr Martinac was the leader of a group of researchers at the University of Wisconsin - Madison , who succeeded in cloning MscL, the first MS channel identified at the molecular level. To date over twenty laboratories in Australia , Europe, the USA and Japan have been using MscL as a prototype MS channel for structural and functional studies of molecular principles of mechanosensory transduction in living cells. The major aim of Dr Martinac's research carried out at the University of Western Australia is to elucidate the role of mechanical force in biophysics of ion channels, and to understand the evolutionary origins of mechanosensensory transduction at the molecular level.

Other evidence of impact and contributions to the field

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Honours and awards:

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• 1976 - 1980 PhD Fellowship Nuclear Research Center , Jülich , Germany .
• 1980 - 1983 Postdoctoral Research Fellowship, Deutsche Forschungsgemeinschaft (SFB 114), Germany .
• 1995 - Research Fellowship for Visiting Scientists by the French Ministry of Research and Higher Education.
• 1995 - Member of the IUAPB Delegation Visiting China .
• 1996 - Invited Member of the Editorial Board of the Croatian Medical Journal
• 1998 - Invited Professor, Université Paris-Sud, Orsay , France .
• 1998 - 2002 State Representative for WA of the Australian Society for Biophysics.
• 1998 - Excellence in Teaching Award for best Coursework Unit (Pharmacology 200).
• 2001 - 2003 Reader for the Australian Research Council.
• 2002 - Elected Vice-President of the Australian Society for Biophysics.
• 2003 - Barbara Ell Seminar Series Lecturer, Victor Chang Cardiac Research Institute, Sydney , Australia .
• 1988 - present Invitations to national and international symposia and conferences (30 in total).
• 1988 - present Invited presentations at universities and research centres in Europe, USA and Australia (40 in total).

Publications - Last 5 years

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• Martinac, B . Mechanosensitive ion channels: Molecules of mechanotransduction. J. Cell Sci. 2004 (in press).

• Park, K.H., Berrier, C., Martinac, B . and Ghazi, A. Purification and functional reconstitution of N- and C-halves of the MscL channel. Biophys. J. 2004 (in press).

• Martinac, B . and Kloda, A. Evolutionary origins of mechanosensitive ion channels. Progress Biophys. Mol. Biol. 82: 11-24, 2003.

• Macdonald, A. G., Martinac, B . and Bartlett, D. H. Patch clamp experiments with porins extracted from a marine bacterium (Photobacterium profundum strain SS9) and reconstituted in liposomes. Cell Biochem. Biophys. 37: 157-168, 2002.

• Macdonald, A.G. Martinac, B. and Bartlett, D.H.: High pressure expriments with the porins from the barophile Photobacterium profundum SS9. Trends in High Pressure Bioscience and Biotechnology, R. Hayashi (ed.) pp. 311-316, 2002.

• Perozo, E., Cortes, D.M., Sompornpisut, P. Kloda, A. and Martinac, B . Structure of MscL in the open state and the molecular mechanism of gating in mechanosensitive channels. Nature 418: 942-948, 2002.

• Perozo, E., Kloda, A., Cortes, D.M. and Martinac, B . Physical principles underlying the transduction of bilayer deformation forces during mechanosensitive channel gating. Nature Struct. Biol. 9: 696-703, 2002.

• Martinac, B . and Hamill, O.P.: Gramicidin A channels can switch between stretch-activation and stretch-inactivation depending upon bilayer thickness. Proc. Natl. Acad. Sci. USA 99: 4308-4312, 2002.

• Dobson, J., Stewart, Z. and Martinac, B .: Preliminary evidence for weak-field

• magnetic effect on mechanosensitive ion channel sub-conducting states in E. coli. Electromagnetic Biology and Medicine 21: 89-95, 2002.

• Kloda, A. and Martinac, B .: Mechanosensitive channels of bacteria and archaea share a common ancestral origin. European Biophys. J. 36: 14-25, 2002.

• Kloda, A. and Martinac, B .: Common evolutionary origins of mechanosensitive ionchannels in archaea, bacteria and cell-walled eukaryotic organisms. Archaea 1: 35-44, 2002.

• Perozo, E., Kloda, A., Cortes, D.M. and Martinac, B .: Site-directed spin-labeling analysis of reconstituted MscL in the closed state. J. Gen. Physiol. 118: 193-206, 2001.

• Kloda, A. and Martinac, B .: Structural and functional similarities and differences between MscMJLR and MscMJ, two homologous MS channels of M. jannashii. EMBO J. 20: 1888-1896, 2001.

• Kloda, A. and Martinac, B .: Mechanosensitive ion channels in Archaea. Cell Biochem. Biophys. 34: 349-381, 2001.

• Kloda, A. and Martinac, B .: Mechanosensitive channel in Thermoplasma a cell wall-less Archaea: cloning and molecular characterization. Cell Biochem. Biophys. 34: 321-347, 2001.

• Martinac, B .: Mechanosensitive channels in prokaryotes. Cellular Physiol. Biochem. 11: 61-76, 2001.

• Hamill, O. P. and Martinac, B .: Molecular basis of mechanotransduction in living cells.Physiol. Rev. 81: 685-740, 2001.

• Kloda, A. and Martinac, B .: Molecular identification of a mechanosensitive ion channel in Archaea. Biophys. J. 80: 229-240, 2001.

• Stewart, Z., Martinac, B . and Dobson, J. : Evidence for mechanosensitive trans-membrane ion channels of small conductance in magnetotactic bacteria. Electro- and Magnetobiology 19: 81-89, 2000.

• Ajouz, B., Berrier, C., Besnard, M., Martinac, B . and Ghazi, A.: Contributions of the different extramembranous domains of the mechanosensitive ion channel MscL to its response to membrane tension. J. Biol. Chem. 275: 1015-1022, 2000.

• Martinac, B .: Mechanosensitive ion channels: universal biological transducers of mechanical stimuli. Australian Biochemist (Showcase in Research) 30: 6-10, 1999 .

• Oakley, A. J., Martinac, B . and Wilce, M. C. J.: Structure and function of the bacterial mechanosensitive channel of large conductance. Protein Science 8: 1915-1921, 1999.

• Macdonald, A.G. and Martinac, B .: Effect of high hydrostatic pressure on the porin OmpC from E. coli. FEMS Microbiol. Letters, 173: 327-334, 1999.

• Saimi, Y., Loukin, S., Zhou, X.-L., Martinac, B . and Kung, C.: Ion channels of Microbes - A Forward Genetics Approach. In: Methods in Enzymology, vol 294 Ion Channels, Part C (ed. P.M. Conn) Academic Press, San Diego, CA, pp 507-524, 1999.

• Blount, P., Sukharev, S., Martinac, B. and Kung, C.: Mechanosensitive channels in bacteria. In: Methods in Enzymology, vol. 294 Ion Channels, Part C (ed. P.M. Conn) Academic Press, San Diego , CA , pp 458-482, 1999.

Ten career-best publications

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1. Martinac, B., Buechner, M., Delcour, A.H.., Adler, J. & Kung, C. : Pressure-sensitive ion channel in Escherichia coli. Proc. Natl. Acad. Sci. USA 84: 2297-2301, 1987.

2. Gustin, M. C., Zhou, X. L., Martinac, B. and Kung, C.: A mechanosensitive ion channel in the yeast plasma membrane. Science 242: 762-765, 1988.

3. Martinac, B., Adler, J. & Kung, C.: Mechanosensitive ion channels of E. coli activated by amphipaths. Nature 348: 261-263, 1990.

4. Sukharev, S.I., Blount, P., Martinac, B. , Blattner, F.R., & Kung, C. : mscLalone encodes a functional large-conductance mechanosensitive channel in E. coli. Nature, 368: 265-268, 1994.

5. Perozo, E., Kloda, A., Cortes, D.A. and Martinac, B .: Site-directed spin-labeling analysis of reconstituted MscL in the closed state. J. Gen. Physiol. 118: 193-206, 2001.

6. Kloda, A. and Martinac, B.: Structural and functional similarities and differences between MscMJLR and MscMJ, two homologous MS channels of M. jannashii. EMBO J. 20: 1888-1896, 2001.

7. Hamill, O. P. and Martinac, B.: Molecular basis of mechanotransduction in living cells. Physiol. Rev. 81: 685-740, 2001.

8. Martinac, B. and Hamill, O.P.: Gramicidin A channels can switch between stretch-activation and stretch-inactivation depending upon bilayer thickness. Proc. Natl. Acad. Sci. USA 99: 4308-4312, 2002.

9. Perozo, E., Kloda, A., Cortes, D.M. and Martinac, B. Physical principles underlying the transduction of bilayer deformation forces during mechanosensitive channel gating. Nature Struct. Biol. 9: 696-703, 2002.

10. Perozo, E., Cortes, D.M., Sompornpisut, P. Kloda, A. and Martinac, B. Structure of MscL in the open state and the molecular mechanism of gating in mechanosensitive channels. Nature 418: 942-948, 2002.