Staff profile

Professor Michael Ryan

Professor

Faculty of Science, Technology and Engineering
School of Molecular Sciences
Department of Biochemistry
La Trobe Institute for Molecular Science

LIMS1 Room 525, Melbourne (Bundoora)

Qualifications

BSc Hons, PhD La Trobe

Membership of professional associations

Australian Society for Biochemistry and Molecular Biology (president elect)

Area of study

Biochemistry and Molecular Biology
Biomedical Science

Brief profile

Mike’s research career has focused on understanding mitochondrial function. With an Alexander von Humboldt fellowship, he was a group leader in the Pfanner laboratory, Germany. Using reconstitution studies, he contributed to discovering that Tom40 is the outer membrane protein translocase channel (Hill et al., Nature 1998), and Tom22 is the organizer of the TOM complex (van Wilpe, Ryan et al. Nature 1999, equal 1st author). Through a detailed import and assembly study, he led the characterisation of subunit assembly into the TOM complex (Model et al., Nat. Struct. Biol., 2001). This work subsequently led to a novel pathway for Tom40 assembly resulting in the identification of the SAM machinery for the assembly of beta-barrel proteins (Wiedemann et al., Nature 2003). Mike has been involved in a number of studies into the biogenesis of metabolite carrier proteins (Ryan et al., JBC 1999; Wiedemann et al., EMBO J 2001) and more recently, the structure and function of the small TIM proteins (Webb et al., Mol. Cell 2006). His work on assembly of membrane protein complexes extended to understanding the assembly of respiratory chain complex I and defects in disease. This has led to a number of high impact publications (e.g. Dunning et al., EMBO J 2007; Kirby et al J. Clin. Invest. 2004,; Lazarou et al., Mol. Cell. Biol. 2007; Tucker et al., Cell Metabolism 2011; Stroud et al.,2013 JBC ). His research has also expanded to understand the dynamics of mitochondria in health and disease (Stojanovski et al., J. Cell. Sci. 2004 ; Lazarou et al. JBC 2010; Palmer et al., EMBO Rep. 2011; Plamer et al., JBC 2013). Mike’s publications have been highly cited and he has an H-index of 40 (Thomson Reuters http://www.researcherid.com/rid/C-6673-2011) or 44 (Google scholar http://scholar.google.com.au/citations?user=lrr21M4AAAAJ&hl=en&oi=ao ).

Since 2000, Mike has supervised 8 PhD student and 27 honours student completions. His students have received numerous poster prizes and other awards. For example, two of his students recently won poster prizes at the 2013 Lorne Conference on Protein Structure and Function and his former student and current postdoc, Dr Catherine Palmer, was awarded the 2013 Fred CollinsASBMB Travel Fellowship award for work conducted during her PhD. Six of his PhD students have undertaken postdoctoral work overseas with two receiving prestigious Alexander von Humboldt fellowships and another working at the NIH (Bethesda, USA). Mike also helps mentor ECRs involved in mitochondrial research including former lab members Mat McKenzie (former NHMRC CDA fellow, now Future Fellow at Monash), Dr Diana Stojanovski (group leader at U Melb), Dr Ann Frazier (Human Frontiers Fellow and now CDA1 fellow, MCRI) and Dr Michael Lazarou (NIH postdoctoral fellow) along with members of his current team including David Stroud (NHMRC fellowship).

Mike maintains a full lecturing load and undertakes various administrative tasks including as Head of the Department of Biochemistry (2010-2013).  Mike has also been appointed President-elect of the Australian Society for Biochemistry and Molecular Biology (ASBMB).

Other achievements:

- H-factor: 40 (ThosonReuters) or 44 (Google scholar)

- 2006 Roche Medal and Plenary lecture, awarded by the Australian Society for Biochemistry & Molecular Biology to an “outstanding Australian biochemist or molecular biologist with less than 15 years postdoctoral experience”.

- Member of the Australian Mitochondrial Diseases Foundation (AMDF) Scientific & Medical Advisory Board

- Executive Member of the ARC Centre of Excellence for Coherent X-Ray Science (2005-2013) and Head of Biology program

- Advisory Board Member, La Trobe Institute for Molecular Science (2010-2013)

- Alexander von Humboldt Research Fellow (1997 – 1998)  - Head of Program Committee for OzBio2010 incorporating IUBMB, FAOBMB and ComBio (ASBMB, APP and ASCB societies), Melbourne Convention Centre, 1600 delegates

- Secretary and Executive member of the Organising Committee, Annual Lorne Conference on Protein Structure & Function (2007-2010) and member of the Program Committee (2005-2013)

- 2012-2017: Member of the Editorial Board for The Journal of Biological Chemistry  

Research interests

Mitochondria biogenesis and disease

- Assembly of membrane protein complexes in health and disease

Teaching units

Mike lectures into Biochemistry and Molecular Biology at second and third year levels.

Recent publications

Tucker EJ, Wanschers BF, Szklarczyk R, Mountford HS, Wijeyeratne XW, van den Brand MA, Leenders AM, Rodenburg RJ, Reljić B, Compton AG, Frazier AE, Bruno DL,  Christodoulou J, Endo H, Ryan MT, Nijtmans LG, Huynen MA, Thorburn DR. Mutations in the UQCC1-Interacting Protein, UQCC2, Cause Human Complex III Deficiency Associated with Perturbed Cytochrome b Protein Expression. PLoS Genet. 2013 Dec;9(12):e1004034. doi: 10.1371/journal.pgen.1004034.

Stroud DA, Ryan MT. Mitochondria: organization of respiratory chain complexes becomes "cristae-lized". Curr Biol. 2013 Nov 4;23(21):R969-71.

Palmer CS, Elgass KD, Parton RG, Osellame LD, Stojanovski D, Ryan MT. Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission. J Biol Chem. 2013 Sep 20;288(38):27584-93.

Ma S, Hockings C, Anwari K, Kratina T, Fennell S, Lazarou M, Ryan MT, Kluck RM, Dewson G. Assembly of the Bak apoptotic pore: a critical role for the Bak protein α6 helix in the multimerization of homodimers during apoptosis. J Biol Chem. 2013 Sep 6;288(36):26027-38. doi: 10.1074/jbc.M113.490094.

Gene Knockout Using Transcription Activator-like Effector Nucleases (TALENs) Reveals That Human NDUFA9 Protein Is Essential for Stabilizing the Junction between Membrane and Matrix Arms of Complex I. Stroud DA, Formosa LE, Wijeyeratne XW, Nguyen TN, Ryan MT. J Biol Chem. 2013 18;288(3):1685-90.

 

Mitochondrial dysfunction in a novel form of autosomal recessive ataxia. Murad NA, Cullen JK, McKenzie M, Ryan MT, Thorburn D, Gueven N, Kobayashi J, Birrell G, Yang J, Dörk T, Becherel O, Grattan-Smith P, Lavin MF. Mitochondrion. 2012 Nov 22. doi:pii: S1567-7249(12)00254-1. 

 

Impaired folding of the mitochondrial small TIM chaperones induces clearance by the i-AAA protease. Baker MJ, Mooga VP, Guiard B, Langer T, Ryan MT, Stojanovski D. J Mol Biol. 2012 Dec 14;424(5):227-39.

 

Mitofusins 'bridge' the gap between oxidative stress and mitochondrial hyperfusion. Ryan MT, Stojanovski D. EMBO Rep. 2012 Oct;13(10):870-1. 

 

Recent advances into the understanding of mitochondrial fission. Elgass K, Pakay J, Ryan MT, Palmer CS. Biochim Biophys Acta. 2013 Jan;1833(1):150-61.

 

Proteomic and Metabolomic Analyses of Mitochondrial Complex I-deficient Mouse Model Generated by Spontaneous B2 Short Interspersed Nuclear Element (SINE) Insertion into NADH Dehydrogenase (Ubiquinone) Fe-S Protein 4 (Ndufs4) Gene. Leong DW, Komen JC, Hewitt CA, Arnaud E, McKenzie M, Phipson B, Bahlo M, Laskowski A, Kinkel SA, Davey GM, Heath WR, Voss AK, Zahedi RP, Pitt JJ, Chrast R, Sickmann A, Ryan MT, Smyth GK, Thorburn DR, Scott HS. (2012) J Biol Chem. 287, 20652-63.

 

Tissue-specific splicing of an Ndufs6 gene-trap insertion generates a mitochondrial complex I deficiency-specific cardiomyopathy. Ke BX, Pepe S, Grubb DR, Komen JC, Laskowski A, Rodda FA, Hardman BM, Pitt JJ,Ryan MT, Lazarou M, Koleff J, Cheung MM, Smolich JJ, Thorburn DR. (2012) Proc Natl Acad Sci U S A. 109, 6165-70.

Next Generation Sequencing in molecular diagnosis: NUBPL mutations highlight the challenges of variant detection and interpretation. Tucker EJ, Mimaki M, Compton AG, McKenzie M, Ryan MT, Thorburn DR. 2012 Human Mutat. Feb;33(2):411-8.

Understanding mitochondrial complex I assembly in health and disease. Mimaki M, Wang X, McKenzie M, Thorburn DR, Ryan MT. Biochim Biophys Acta. 2011 Mar;1808(3):1002-11.

Mutations in the Gene Encoding C8orf38 Block Complex I Assembly by Inhibiting Production of the Mitochondria-Encoded Subunit ND1. McKenzie M, Tucker EJ, Compton AG, Lazarou M, George C, Thorburn DR, Ryan MT. 2011 J Mol Biol. 2;414(3):413-26.

Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation. Tucker EJ, Hershman SG, Köhrer C, Belcher-Timme CA, Patel J, Goldberger OA, Christodoulou J, Silberstein JM, McKenzie M, Ryan MT, Compton AG, Jaffe JD, Carr SA, Calvo SE, RajBhandary UL, Thorburn DR, Mootha VK. Cell Metab. 2011 Sep 7;14(3):428-34.

The regulation of mitochondrial morphology: intricate mechanisms and dynamic machinery. Palmer CS, Osellame LD, Stojanovski D, Ryan MT. Cell Signal. 2011 Oct;23(10):1534-45.  Review.

MiD49 and MiD51, new components of the mitochondrial fission machinery. Palmer CS, Osellame LD, Laine D, Koutsopoulos OS, Frazier AE, Ryan MT. EMBO Rep. 2011 Jun;12(6):565-73.

Inhibition of Bak activation by VDAC2 is dependent on the Bak transmembrane anchor. Lazarou M, Stojanovski D, Frazier AE, Kotevski A, Dewson G, Craigen WJ, Kluck RM, Vaux DL, Ryan MT. J Biol Chem. 2010 Nov 19;285(47):36876-83.

Mitochondrial protein import machineries and lipids: A functional connection. Gebert N, Ryan MT, Pfanner N, Wiedemann N, Stojanovski D. Biochim Biophys Acta. 2010 Aug 7.

Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome. Riley LG, Cooper S, Hickey P, Rudinger-Thirion J, McKenzie M, Compton A, Lim SC, Thorburn D, Ryan MT, Giegé R, Bahlo M, Christodoulou J. Am J Hum Genet. 2010 Jul 9;87(1):52-9.

Assembly factors of human mitochondrial complex I and their defects in disease. Mckenzie M, Ryan MT. IUBMB Life. 2010 Jul;62(7):497-502.

Human Miltons associate with mitochondria and induce microtubule-dependent remodeling of mitochondrial networks. Koutsopoulos OS, Laine D, Osellame L, Chudakov DM, Parton RG, Frazier AE, Ryan MT. Biochim Biophys Acta. 2010 May;1803(5):564-74. Epub 2010 Mar 15.

Mitochondrial cardiolipin involved in outer-membrane protein biogenesis: implications for Barth syndrome. Gebert N, Joshi AS, Kutik S, Becker T, McKenzie M, Guan XL, Mooga VP, Stroud DA, Kulkarni G, Wenk MR, Rehling P, Meisinger C, Ryan MT, Wiedemann N, Greenberg ML, Pfanner N. Curr Biol. 2009 Dec 29;19(24):2133-9

Assembly of nuclear DNA-encoded subunits into mitochondrial complex IV, and their preferential integration into supercomplex forms in patient mitochondria. Lazarou M, Smith SM, Thorburn DR, Ryan MT, McKenzie M. FEBS J. 2009 276(22): 6427 - 6824

Chapter 18 Analysis of respiratory chain complex assembly with radiolabeled nuclear and mitochondrial encoded subunits. McKenzie M, Lazarou M, Ryan MT. Methods Enzymol. 2009. 456:321-39.

Assembly of mitochondrial complex I and defects in disease. Lazarou M, Thorburn DR, Ryan MT, McKenzie M. Biochim Biophys Acta. 2009 1793(1):78-88.

Structural and functional requirements for activity of the Tim9-Tim10 complex in mitochondrial protein import. Baker MJ, Webb CT, Stroud DA, Palmer CS, Frazier AE, Guiard B, Chacinska A, Gulbis JM, Ryan MT. Mol. Biol. Cell. 2009 20(3):769-79. Epub 2008 Nov 26.

Structural and functional requirements for activity of the Tim9-Tim10 complex in mitochondrial protein import. Mutation of C20orf7 disrupts complex I assembly and causes lethal neonatal mitochondrial disease. Sugiana C, Pagliarini DJ, McKenzie M, Kirby DM, Salemi R, Abu-Amero KK, Dahl HH, Hutchison WM, Vascotto KA, Smith SM, Newbold RF, Christodoulou J, Calvo S, Mootha VK, Ryan MT, Thorburn DR. Am J Hum Genet. 2008 83(4):468-78.

Mitochondrial protein import: precursor oxidation in a ternary complex with disulfide carrier and sulfhydryl oxidase. Stojanovski D, Milenkovic D, Müller JM, Gabriel K, Schulze-Specking A, Baker MJ, Ryan MT, Guiard B, Pfanner N, Chacinska A. J Cell Biol. 2008 183(2):195-202.

Mitochondrial protein-import machinery: correlating structure with function. Baker MJ, Frazier AE, Gulbis JM, Ryan MT. Trends Cell Biol. 2007 17(9):456-64. Review.

Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease. Dunning CJ, McKenzie M, Sugiana C, Lazarou M, Silke J, Connelly A, Fletcher JM, Kirby DM, Thorburn DR, Ryan MT. EMBO J. 2007 26(13):3227-37.

Analysis of the assembly profiles for mitochondrial- and nuclear-DNA-encoded subunits into complex I. Lazarou M, McKenzie M, Ohtake A, Thorburn DR, Ryan MT. Mol Cell Biol. 2007 27(12):4228-37.

Analysis of mitochondrial subunit assembly into respiratory chain complexes using Blue Native polyacrylamide gel electrophoresis. McKenzie M, Lazarou M, Thorburn DR, Ryan MT. Anal Biochem. 2007 364(2):128-37.

 

Research projects