Professor Phillip Robinson

Professor
Medicine, Children's Medical Research Institute

C29 - Children's Hospital Westmead
The University of Sydney
NSW 2006 Australia

T: 02 8865 2915
F: 02 9687 2120
E:

Curriculum vitae

Biographical details

Phil has a B.Sci. (Hons) in Biochemistry from Sydney University and in 1984 he completed a PhD in Medical Biochemistry at the University of Newcastle. After postdoctoral studies at the National Institutes of Health (NIH, USA), Merrell Dow Research Institute Cincinnati, and St. Vincent's Institute of Medical Research Melbourne, he became Principal Hospital Scientist at the John Hunter Hospital Newcastle. He took up his present position as Head of the Cell Signalling Unit at the Children’s Medical Research Institute (CMRI) Sydney in 1996 and is also a Professor in Medicine at the Universities of Sydney and Newcastle, and is one of only ~70 Australian scientists holding a Principal Research Fellowship from the NHMRC. He leads a team of 21 scientists, postdocs and graduate students.

Research interests

His research program focuses on understanding the molecular mechanisms of synaptic transmission in the nervous system. His work brings together cell signalling with protein chemistry and medicinal chemistries to: a) understand the basic science of nerve communication and b) develop drugs to control diseases of nerve terminals like epilepsy. Nerve communication involves neurotransmitter release at contact points between nerves – synapses. It occurs from small storage vesicles, synaptic vesicles, which accumulate at synapses. They must be recycled locally or synaptic transmission stops, resulting in paralysis. The main focus is on proteins called the dynamins, which are self-assembling molecular machines acting in many intracellular functions. Dynamin can self-assemble as a helix at the neck of newly forming synaptic vesicles to cut it free into the cell a process called endocytosis. There are three dynamin genes: dynI (neuron specific), dynII (ubiquitously expressed) and dynIII (low levels in neurons and testes) and dynII mutations cause Charcot-Marie Tooth neurodegeneration, the muscle disease Centronuclear Myopathy and childhood leukaemia.


Phil and his team have made many discoveries about the molecular mechanisms of endocytosis at the synapse. His work revealed that synaptic vesicle endocytosis is a highly regulated process in neurons, triggered by protein dephosphorylation. He uses mass spectrometry for phosphoproteomics to identify all phosphosites in all endocytic proteins and to rank them by abundance and physiological relevance. By working together with the Medicinal Chemist, Adam McCluskey, at the University of Newcastle they have utilised the new knowledge to develop potential new drugs. This represents part of an overall strategy to develop dynamin and endocytosis inhibitors: a) as tools for medical researchers to solve significant biological problems, and b) as potential candidate therapeutics for human disease indications in which harnessing endocytosis pathways may alleviate disease symptoms for epilepsy, cancer, infectious diseases and chronic kidney disease.

Current national competitive grants*

2012

The role of clathrin in the spindle assembly checkpoint and as an anti-cancer target
Chircop M, Robinson P, McCluskey A, Sakoff J
NHMRC Project Grants ($629,685 over 3 years)

Mechanism of action of dynamin ring stabilizer compounds controlling the actin cytoskeleton
Robinson P, McCluskey A
NHMRC Project Grants ($637,020 over 3 years)

* Grants administered through the University of Sydney

Keywords

Cell biology; Biochemistry; Neuropharmacology; Neurosciences; Epilepsy

Publications

2014 | 2013 | 2012 | 2011 | 2010 | 2009 | 2008

2014

   
  • Macgregor, K., Robertson, M., Young, K., von Kleist, L., Stahlschmidt, W., Whiting, A., Chau, N., Robinson, P., Haucke, V., McCluskey, A. (2014), Development of 1,8-Naphthalimides as Clathrin Inhibitors. Journal of Medicinal Chemistry. 57, 131-143. [Abstract]

2013

   
  • McCluskey, A., Daniel, J., Hadzic, G., Chau, N., Clayton, E., Mariana, A., Whiting, A., Gorgani, N., Lloyd, J., Quan, A., Moshkanbaryans, L., Krishnan, S., Perera, S., Chircop, M., von Kleist, L., McGeachie, A., Howes, M., Parton, R., Campbell, M., Sakoff, J., Wang, X., Sun, J., Robertson, M., Deane, F., Nguyen, T., Meunier, F., Cousin, M., Robinson, P. (2013), Building a better dynasore: the dyngo compounds potently inhibit dynamin and endocytosis. Traffic. 14(12), 1272-1289. [Abstract]
  • Anggono, V., Koc-Schmitz, Y., Widagdo, J., Kormann, J., Quan, A., Chen, C., Robinson, P., Choi, S., Linden, D., Plomann, M., Huganir, R. (2013), PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression. Proceedings of the National Academy of Sciences of the United States of America. 110(34), 13976-13981. [Abstract]
  • McGeachie, A., Odell, L., Quan, A., Daniel, J., Chau, N., Hill, T., Gorgani, N., Keating, D., Cousin, M., van Dam, E., Mariana, A., Whiting, A., Perera, S., Novelle, A., Young, K., Deane, F., Gilbert, J., Sakoff, J., Chircop, M., McCluskey, A., Robinson, P. (2013), Pyrimidyn Compounds: Dual-Action Small Molecule Pyrimidine-Based Dynamin Inhibitors. ACS Chemical Biology. 8(7), 1507-1518. [Abstract]
  • Quan, A., Robinson, P. (2013), Syndapin, a membrane remodelling and endocytic F-BAR protein. The FEBS Journal. 280(21), 5198-5212. [Abstract]
  • Harper, C., Popoff, M., McCluskey, A., Robinson, P., Meunier, F. (2013), Targeting membrane trafficking in infection prophylaxis: dynamin inhibitors. Trends in Cell Biology. 23(2), 90-101. [Abstract]
  • Gordon, C., Venn-Brown, B., Robertson, M., Young, K., Chau, N., Mariana, A., Whiting, A., Chircop, M., Robinson, P., McCluskey, A. (2013), Development of second-generation indole-based dynamin GTPase inhibitors. Journal of Medicinal Chemistry. 56(1), 46-59. [Abstract]
  • Smith, C., Haucke, V., McCluskey, A., Robinson, P., Chircop, M. (2013), Inhibition of clathrin by pitstop 2 activates the spindle assembly checkpoint and induces cell death in dividing HeLa cancer cells. Molecular Cancer. 12, 4. [Abstract]
  • Ma, M., Robinson, P., Chircop, M. (2013), Sorting nexin 9 recruits clathrin heavy chain to the mitotic spindle for chromosome alignment and segregation. PloS One. 8(7), e68387. [Abstract]

2012

   
  • Reid, A., Lord, T., Stanger, S., Roman, S., McCluskey, A., Robinson, P., Aitken, R., Nixon, B. (2012), Dynamin regulates specific membrane fusion events necessary for acrosomal exocytosis in mouse spermatozoa. Journal of Biological Chemistry. 287(45), 37659-37672. [Abstract]
  • Bolderson, E., Savage, K., Mahen, R., Pisupati, V., Graham, M., Richard, D., Robinson, P., Venkitaraman, A., Khanna, K. (2012), Kruppel-associated Box (KRAB)-associated co-repressor (KAP-1) Ser-473 phosphorylation regulates heterochromatin protein 1β (HP1-β) mobilization and DNA repair in heterochromatin. Journal of Biological Chemistry. 287(33), 28122-28131. [Abstract]
  • Luwor, R., Chin, X., McGeachie, A., Robinson, P., Zhu, H. (2012), Dynamin II function is required for EGF-mediated Stat3 activation but not Erk1/2 phosphorylation. Growth Factors. 30(4), 220-229. [Abstract]
  • Graham, M., Stone, R., Robinson, P., Payne, R. (2012), Synthesis and protein binding studies of a peptide fragment of clathrin assembly protein AP180 bearing an O-linked β-N-acetylglucosaminyl-6-phosphate modification. Organic & Biomolecular Chemistry. 10(13), 2545-2551. [Abstract]
  • Quan, A., Xue, J., Wielens, J., Smillie, K., Anggono, V., Parker, M., Cousin, M., Graham, M., Robinson, P. (2012), Phosphorylation of syndapin I F-BAR domain at two helix-capping motifs regulates membrane tubulation. Proceedings of the National Academy of Sciences of the United States of America. 109(10), 3760-3765. [Abstract]
  • Smith, C., Bensing, S., Burns, C., Robinson, P., Kasperlik-Zaluska, A., Scott, R., K��mpe, O., Crock, P. (2012), Identification of TPIT and other novel autoantigens in lymphocytic hypophysitis: immunoscreening of a pituitary cDNA library and development of immunoprecipitation assays. European Journal of Endocrinology. 166(3), 391-398. [Abstract]
  • Robertson, M., Hadzic, G., Ambrus, J., Pomè, D., Hyde, E., Whiting, A., Mariana, A., von Kleist, L., Chau, N., Haucke, V., Robinson, P., McCluskey, A. (2012), The Rhodadyns, a new class of small molecule inhibitors of dynamin gtpase activity. ACS Medicinal Chemistry Letters. 3(5), 352-356.
  • Nguyen, T., Maucort, G., Sullivan, R., Schenning, M., Lavidis, N., McCluskey, A., Robinson, P., Meunier, F. (2012), Actin- and dynamin-dependent maturation of bulk endocytosis restores neurotransmission following synaptic depletion. PLoS One. 7(5), e36913. [Abstract]
  • Daniel, J., Malladi, C., Kettle, E., McCluskey, A., Robinson, P. (2012), Analysis of synaptic vesicle endocytosis in synaptosomes by high-content screening. Nature Protocols. 7(8), 1439-1455. [Abstract]
  • Brymora, A., Duggin, I., Berven, L., van Dam, E., Roufogalis, B., Robinson, P. (2012), Identification and Characterisation of the RalA-ERp57 Interaction: Evidence for GDI Activity of ERp57. PLoS One. 7(11), e50879. [Abstract]

2011

   
  • Nguyen, M., Joya, J., Kee, A., Domazetovska, A., Yang, N., Hook, J., Lemckert, F., Kettle, E., Valova, V., Robinson, P., North, K., Gunning, P., Mitchell, C., Hardeman, E. (2011), Hypertrophy and dietary tyrosine ameliorate the phenotypes of a mouse model of severe nemaline myopathy. Brain. 134(Pt 12), 3516-3529. [Abstract]
  • Harper, C., Martin, S., Nguyen, T., Daniels, S., Lavidis, N., Popoff, M., Hadzic, G., Mariana, A., Chau, N., McCluskey, A., Robinson, P., Meunier, F. (2011), Dynamin inhibition blocks botulinum neurotoxin type A endocytosis in neurons and delays botulism. The Journal of Biological Chemistry. 286(41), 35966-35976. [Abstract]
  • Chircop, M., Sarcevic, B., Larsen, M., Malladi, C., Chau, N., Zavortink, M., Smith, C., Quan, A., Anggono, V., Hainsa, P., Graham, M., Robinson, P. (2011), Phosphorylation of dynamin II at serine-764 is associated with cytokinesis. Biochimica et biophysica acta. 1813(10), 1689-99. [Abstract]
  • Xue, J., Graham, M., Novelle, A., Sue, N., Gray, N., McNiven, M., Smillie, K., Cousin, M., Robinson, P. (2011), Calcineurin Selectively Docks with the Dynamin Ixb Splice Variant to Regulate Activity-dependent Bulk Endocytosis. Journal of Biological Chemistry. 286(35), 30295-30303. [Abstract]
  • Chircop, M., Perera, S., Mariana, A., Lau, H., Ma, M., Gilbert, J., Jones, N., Gordon, C., Young, K., Morokoff, A., Sakoff, J., O'Brien, T., McCluskey, A., Robinson, P. (2011), Inhibition of dynamin by dynole 34-2 induces cell death following cytokinesis failure in cancer cells. Molecular cancer therapeutics. 10(9), 1553-62. [Abstract]
  • von Kleist, L., Stahlschmidt, W., Bulut, H., Gromova, K., Puchkov, D., Robertson, M., MacGregor, K., Tomilin, N., Tomlin, N., Pechstein, A., Chau, N., Chircop, M., Sakoff, J., von Kries, J., Saenger, W., Kräusslich, H., Shupliakov, O., Robinson, P., McCluskey, A., Haucke, V. (2011), Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition. Cell. 146(3), 471-484. [Abstract]
  • Graham, M., Thaysen-Andersen, M., Bache, N., Craft, G., Larsen, M., Packer, N., Robinson, P. (2011), A Novel Post-translational Modification in Nerve Terminals: O-Linked N-Acetylglucosamine Phosphorylation. Journal of Proteome Research. 10(6), 2725-2733. [Abstract]
  • Kozlov, S., Graham, M., Jakob, B., Tobias, F., Kijas, A., Tanuji, M., Chen, P., Robinson, P., Taucher-Scholz, G., Suzuki, K., So, S., Chen, D., Lavin, M. (2011), Autophosphorylation and ATM activation: additional sites add to the complexity. The Journal of Biological Chemistry. 286(11), 9107-9119. [Abstract]
  • Joshi, S., Braithwaite, A., Robinson, P., Chircop, M. (2011), Dynamin inhibitors induce caspase-mediated apoptosis following cytokinesis failure in human cancer cells and this is blocked by Bcl-2 overexpression. Molecular Cancer. 10, 78. [Abstract]
  • Woolley, A., Algie, M., Samuel, W., Harfoot, R., Wiles, A., Hung, N., Tan, P., Hains, P., Valova, V., Huschtscha, L., Royds, J., Perez, D., Yoon, H., Cohen, S., Robinson, P., Bay, B., Lasham, A., Braithwaite, A. (2011), Prognostic association of YB-1 expression in breast cancers: a matter of antibody. PLoS One. 6(6), e20603. [Abstract]

2010

   
  • Chircop, M., Malladi, C., Lian, A., Page, S., Zavortink, M., Gordon, C., McCluskey, A., Robinson, P. (2010), Calcineurin activity is required for the completion of cytokinesis. Cellular and molecular life sciences : CMLS. 67, 3725-37. [Abstract]
  • Chan, L., Hansra, G., Robinson, P., Graham, M. (2010), Differential Phosphorylation of Dynamin I Isoforms in Subcellular Compartments Demonstrates the Hidden Complexity of Phosphoproteomes. Journal of proteome research. 9(8), 4028-37. [Abstract]
  • Joshi, S., Perera, S., Gilbert, J., Smith, C., Mariana, A., Gordon, C., Sakoff, J., McCluskey, A., Robinson, P., Braithwaite, A., Chircop Nee Fabbro, M. (2010), The Dynamin Inhibitors MiTMAB and OcTMAB Induce Cytokinesis Failure and Inhibit Cell Proliferation in Human Cancer Cells. Molecular cancer therapeutics. 9(7), 1995-2006. [Abstract]
  • Clayton, E., Sue, N., Smillie, K., O'Leary, T., Bache, N., Cheung, G., Cole, A., Wyllie, D., Sutherland, C., Robinson, P., Cousin, M. (2010), Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles. Nature neuroscience. 13, 845-51. [Abstract]
  • Sandgren, K., Wilkinson, J., Miranda-Saksena, M., McInerney, G., Byth-Wilson, K., Robinson, P., Cunningham, A. (2010), A differential role for macropinocytosis in mediating entry of the two forms of vaccinia virus into dendritic cells. PLoS pathogens. 6(4), e1000866. [Abstract]
  • Susman, R., Quijano-Roy, S., Yang, N., Webster, R., Clarke, N., Dowling, J., Kennerson, M., Nicholson, G., Biancalana, V., Ilkovski, B., Flanigan, K., Arbuckle, S., Malladi, C., Robinson, P., Vucic, S., Mayer, M., Romero, N., Urtizberea, J., García-Bragado, F., Guicheney, P., Bitoun, M., Carlier, R., North, K. (2010), Expanding the clinical, pathological and MRI phenotype of DNM2-related centronuclear myopathy. Neuromuscular Disorders. 20(4), 229-237. [Abstract]
  • Baker, M., Smith, N., Hetherington, L., Taubman, K., Graham, M., Robinson, P., Aitken, R. (2010), Label-free quantitation of phosphopeptide changes during rat sperm capacitation. Journal of Proteome Research. 9(2), 718-729. [Abstract]
  • Cohen, S., Ma, W., Valova, V., Algie, M., Harfoot, R., Woolley, A., Robinson, P., Braithwaite, A. (2010), Genotoxic stress-induced nuclear localization of oncoprotein YB-1 in the absence of proteolytic processing. Oncogene. 29(3), 403-10. [Abstract]
  • Odell, L., Howan, D., Gordon, C., Robertson, M., Chau, N., Mariana, A., Whiting, A., Abagyan, R., Daniel, J., Gorgani, N., Robinson, P., McCluskey, A. (2010), The Pthaladyns: GTP Competitive Inhibitors of Dynamin I and II GTPase Derived from Virtual Screening. Journal of Medicinal Chemistry. 53, 5267-5280. [Abstract]
  • Hill, T., Mariana, A., Gordon, C., Odell, L., Robertson, M., McGeachie, A., Chau, N., Daniel, J., Gorgani, N., Robinson, P., McCluskey, A. (2010), Iminochromene Inhibitors of Dynamins I and II GTPase Activity and Endocytosis. Journal of Medicinal Chemistry. 53, 4094-4102. [Abstract]
  • Gray, L., Dean, B., Kronsbein, H., Robinson, P., Scarr, E. (2010), Region and diagnosis-specific changes in synaptic proteins in schizophrenia and bipolar I disorder. Psychiatry Research. 178(2), 374-380. [Abstract]
  • Howes, M., Kirkham, M., Riches, J., Cortese, K., Walser, P., Simpson, F., Hill, M., Jones, A., Lundmark, R., Lindsay, M., Hernandez-Deviez, D., Hadzic, G., McCluskey, A., Bashir, R., Liu, L., Pilch, P., McMahon, H., Robinson, P., Hancock, J., Mayor, S., Parton, R. (2010), Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells. Journal of Cell Biology. 190, 675-691. [Abstract]

2009

   
  • Hill, T., Gordon, C., McGeachie, A., Venn-Brown, B., Odell, L., Chau, N., Quan, A., Mariana, A., Sakoff, J., Chircop, M., Robinson, P., McCluskey, A. (2009), Inhibition of dynamin mediated endocytosis by the dynoles--synthesis and functional activity of a family of indoles. Journal of medicinal chemistry. 52(12), 3762-73. [Abstract]
  • Clayton, E., Anggono, V., Smillie, K., Chau, N., Robinson, P., Cousin, M. (2009), The phospho-dependent dynamin-syndapin interaction triggers activity-dependent bulk endocytosis of synaptic vesicles. The Journal of Neuroscience. 29(24), 7706-7717. [Abstract]
  • Chircop, M., Oakes, V., Graham, M., Ma, M., Smith, C., Robinson, P., Khanna, K. (2009), The actin-binding and bundling protein, EPLIN, is required for cytokinesis. Cell Cycle. 8(5), 757-764. [Abstract]
  • Veldhuis, N., Valova, V., Gaeth, A., Palstra, N., Hannan, K., Michell, B., Kelly, L., Jennings, I., Kemp, B., Pearson, R., Robinson, P., Camakaris, J. (2009), Phosphorylation regulates copper-responsive trafficking of the Menkes copper transporting P-type ATPase. International Journal of Biochemistry & Cell Biology. 41(12), 2403-2412. [Abstract]
  • Odell, L., Chau, N., Mariana, A., Graham, M., Robinson, P., McCluskey, A. (2009), Azido and Diazarinyl Analogues of Bis-Tyrphostin as Asymmetrical Inhibitors of Dynamin GTPase. Chemmedchem. 4(7), 1182-1188. [Abstract]
  • Holland, I., McCluskey, A., Sakoff, J., Gilbert, J., Chau, N., Robinson, P., Motti, C., Wright, A., van Altena, I. (2009), Steroids from an Australian Sponge Psammoclema sp. Journal of Natural Products. 72(1), 102-106. [Abstract]

2008

   
  • Tsang, C., Fedchyshyn, M., Harrison, J., Xie, H., Xue, J., Robinson, P., Wang, L., Trimble, W. (2008), Superfluous role of mammalian septins 3 and 5 in neuronal development and synaptic transmission. Molecular and cellular biology. 28(23), 7012-29. [Abstract]
  • Craft, G., Graham, M., Bache, N., Larsen, M., Robinson, P. (2008), The in vivo phosphorylation sites in multiple isoforms of amphiphysin I from rat brain nerve terminals. Molecular & cellular proteomics : MCP. 7(6), 1146-61. [Abstract]
  • Anggono, V., Cousin, M., Robinson, P. (2008), Styryl dye-based synaptic vesicle recycling assay in cultured cerebellar granule neurons. In: Methods in Molecular Biology. (pp.333-345).United States: Humana Press. [Abstract]
  • Thingholm, T., Jensen, O., Robinson, P., Larsen, M. (2008), SIMAC (sequential elution from IMAC), a phosphoproteomics strategy for the rapid separation of monophosphorylated from multiply phosphorylated peptides. Molecular & Cellular Proteomics. 7(4), 661-671. [Abstract]
  • Dunkley, P., Jarvie, P., Robinson, P. (2008), A rapid Percoll gradient procedure for preparation of synaptosomes. Nature Protocols. 3(11), 1718-1728. [Abstract]
  • Zhang, J., Lawrance, G., Chau, N., Robinson, P., McCluskey, A. (2008), From Spanish fly to room-temperature ionic liquids (RTILs): synthesis, thermal stability and inhibition of dynamin 1 GTPase by a novel class of RTILs. New Journal of Chemistry. 32(1), 28-36. [Abstract]