Bob (Robert) ROBINSON   
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  Bob (Robert) ROBINSON  
  Lab Location: #3-15

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  Key Publications  

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Jiang, S., Narita, A., Popp, D., Ghoshdastider, U., Lee, L. J., Srinivasan, R., Mohan K. Balasubramanian, M. K., Oda, T., Koh, F., Larsson, M., & Robinson, R. C.
Novel actin filaments from Bacillus thuringiensis form nanotubules for plasmid DNA segregation.
Proc. Natl. Acad. Sci. U.S.A. (2016) 113, E1200-1205.

Baskaran, Y., Ang, K. C., Anekal, P. V., Chan, W. L., Grimes, J. M., Manser, E., & Robinson, R. C.
An in cellulo derived structure of PAK4 in complex with its inhibitor Inka1..
Nat. Commun. (2015) 6, 8681.

Chumnarnsilpa, S., Robinson, R. C., Grimes, J. M., & Leyrat, C.
Calcium-controlled conformational choreography in the N-terminal half of adseverin.
Nat. Commun. (2015) 6, 8254.

Ghoshdastider, U., Jiang, S. M., Popp, D. & Robinson, R. C.
In search of the primordial actin filament.
Proc. Natl. Acad. Sci. U.S.A. (2015) 112, 9150-9151.

Go, M., Wongsantichon. J., Cheung, V. W. N., Chow, J, Y., Robinson, R. C.* & Yew, W. S.
Synthetic Polyketide Enzymology: A Platform for Biosynthesis of Anti-Microbial Polyketides.
ACS Catal. (2015) 5, 4033-4042.

Gunning, P., Ghoshdastider, U., Whitaker, S., Popp, D. & Robinson, R. C.
The evolution of compositionally and functionally distinct actin filaments.
J. Cell Sci. (2015) 128, 2009-2019.

Lee, W. L., Grimes, J. M. & Robinson, R. C.
Yersinia effector YopO utilizes actin as bait to phosphorylate proteins that regulate actin polymerization.
Nat. Struct. Mol. Biol.  (2015) 22, 248-255.

Van Overbeke, W., Wongsantichon, J., Everaert, I., Verhelle, A., Zwaenepoel, O., Loonchanta, A., Burtnick, L. D., De Ganck, A., Hochepied, T., Haigh, J., Cuvelier, C., Derave, W., Robinson, R. C.* & Gettemans, J.
An ER-directed gelsolin nanobody establishes therapeutic merit in the gelsolin amyloidosis mouse model by shielding mutant plasma gelsolin from furin proteolysis.
Hum. Mol. Genet. (2015) 24, 2492-2450.

Ranok, A., Wongsantichon, J., Robinson, R. C.* and Suginta, W.
Structural and thermodynamic insights into chitooligosaccharide binding to human cartilage chitinase 3-like protein 2 (CHI3L2 or YKL-39).
J. Biol. Chem. (2015) 290, 2617-2629.

Xue, B., Leyrat, C., Grimes, J. M. & Robinson, R. C.
The structural basis of thymosin-β4/profilin exchange leading to actin filament polymerization.
Proc. Natl. Acad. Sci. U.S.A. (2014) 111, E4596-605.

Lv, C., Gao, X., Li, W., Xue, B., Qin, M., Burtnick, L. D., Zhou, H., Cao, Y., Robinson, R. C.* & Wang, W.
Single molecule force spectroscopy reveals force-enhanced binding of calcium ions by gelsolin.
Nat. Commun. (2014) 5, 4623.

Popp, D., Narita, A., Lee, L. J., Larsson, M. & Robinson, R. C.
Microtubule-like properties of the bacterial actin homolog ParM-R1.
J. Biol. Chem. (2012) 287, 37078-37088.

Popp, D., Narita, A., Lee, L. J., Ghoshdastider, U., Xue, B., Srinivasan, R., Balasubramanian, M. K., Tanaka, T. & Robinson, R. C.
A novel actin-like filament structure from Clostridium tetani.
J. Biol. Chem. (2012) 287, 21121-21129.

Hernandez-Valladares, M., Kim, T., Kannan, B., Tung, A., Aguda, A. H., Larsson, M, Cooper, J. A. & Robinson, R. C.
Structural characterization of a capping protein interaction motif defines a family of actin filament regulators.
Nat. Struct. Mol. Biol. (2010) 17, 497-503.

Popp, D., Narita, A., Maeda, K., Fujisawa, T., Ghoshdastider, U., Iwasa, M., Maeda, Y. & Robinson, R. C. Filament structure, organization, and dynamics in MreB sheets.
J. Biol. Chem. (2010) 285, 15858-15865.

Popp, D., Iwasa, M., Erickson, H. P., Narita, A., Maeda, Y. & Robinson, R. C.
Suprastructures and dynamic properties of Mycobacterium tuberculosis FtsZ.
J. Biol. Chem. (2010) 285, 11281-11289.

Popp, D., Xu, W., Narita, A., Brzoska, A. J., Skurray, R. A., Firth, N., Goshdastider, U., Maeda, Y., Robinson, R. C. & Schumacher, M. A.
Structure and filament dynamics of the pSK41 actin-like ParM protein: implications for plasmid DNA segregation.
J. Biol. Chem. (2010) 285, 10130-10140.

Chow, J.Y., Xue, B., Lee, K. H., Tung, A., Wu, L., Robinson, R. C.* & Yew, W. S.
Directed evolution of a thermostable quorum-quenching lactonase from the amidohydrolase superfamily.
J. Biol. Chem. (2010) 285, 40911-40920.

Chumnarnsilpa, S., Lee, W. L., Nag, S., Kannan, B., Larsson, M., Burtnick, L. D. & Robinson, R. C.
The crystal structure of the C-terminus of adseverin reveals the actin-binding interface.
Proc. Natl. Acad. Sci. U.S.A. (2009) 106, 13719-13724.

Nag, S., Ma, Q., Wang, H., Chumnarnsilpa, S., Lee, W. L., Larsson, M., Kannan, B., Hernandez-Valladares, M., Burtnick, L. D. & Robinson, R. C.
Ca2+ binding by domain 2 plays a critical role in the activation and stabilization of gelsolin.
Proc. Natl. Acad. Sci. U.S.A. (2009) 106, 13719-13724.

Wang, H., Chumnarnsilpa, S., Loonchanta, A., Li, Q., Kuan, Y. M., Robine, S., Larsson, M., Mihalek, I., Burtnick, L. D. & Robinson, R. C.
Helix-straightening as an activation mechanism in the gelsolin superfamily of actin regulatory proteins.
J. Biol. Chem. (2009) 284, 21265-21269.

Aguda, A. H., Xue, B., Irobi, E., Preat, T. & Robinson, R. C.
The structural basis of actin interaction with multiple WH2 motif-containing proteins.
Structure (2006) 14, 469-476.

Huang, S., Robinson, R. C., Gao, L. Y., Matsumoto, T., Brunet, A., Blanchoin, L. & Staiger, C. J.
Arabidopsis VILLIN1 generates actin filament cables that are resistant to depolymerization.
Plant Cell
(2005) 17, 486-501.

Irobi, E., Aguda, A. H., Larsson, M., Guerin, C., Yin, H. L., Burtnick, L. D., Blanchoin, L. & Robinson, R. C.
Structural basis of actin sequestration by thymosin-b4: Implications for WH2 proteins.
EMBO J. (2004) 23, 3599-3608.

Burtnick, L. D., Urosev, D., Irobi, E., Narayan, K. & Robinson, R. C.
Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF.
EMBO J. (2004) 23, 2713-272.

Robinson, R. C., Turbedsky, K., Kaiser, D. A., Higgs, H., Marchand, J.-B.  Choe, S. & Pollard, T. D.
Crystal Structure of Arp2/3 Complex.
Science. (2001) 294, 1679-1684.

Robinson, R. C., Choe, S., & Burtnick, L. D.
The disintegration of a molecule: The role of gelsolin in FAF, familial amyloidosis (Finnish type).
Proc. Natl. Acad. Sci. U.S.A. (2001) 98, 2117-2118.

Blanchoin, L., Robinson, R. C., Choe, S. & Pollard, T. D.
Phosphorylation of Acanthamoeba actophorin (ADF/cofilin) blocks interaction with actin without a change in atomic structure.
J. Biol. Chem. (2000) 295, 203-211.

Robinson, R. C., Mejillano, M., Le, V. P., Burtnick, L. D., Yin, H. L. & Choe, S.
Domain movement in a gelsolin activation switch.
Science (1999) 286,1939-1942.

May, A. P., Robinson, R. C., Aplin, R. T., Bradfield, P., Crocker, P. R. & Jones, E. Y.
The structure of a sialic acid binding fragment of sialoadhesin in the presence of ligand.
Mol. Cell  (1998) 1, 719-728.

Burtnick, L. D., Koepf, E. K., Grimes, J., Jones, E. Y., Stuart, D. I., McLaughlin, P. J. & Robinson, R. C.
The crystal structure of plasma gelsolin: Implications for actin severing, capping and nucleation.
Cell (1997) 90, 661-670.

Jones, E. Y., Harlos, K., Bottomley, M. J., Robinson, R. C., Driscoll, P. C., Edwards, J. M., Clements, J. M., Dudgeon, T. J. & Stuart, D. I.
Crystal structure of an integrin-binding fragment of vascular cell adhesion molecule 1 at 1.8 Å resolution.
Nature (1995) 373, 539-544.

Robinson, R. C., Grey, L. M., Staunton, D., Vankelecom, H., Vernallis, A. B., Moreau, J-F., Stuart, D. I., Heath, J. K. & Jones, E. Y.
The crystal structure and biological function of leukaemia inhibitory factor: Implications for receptor binding.
Cell (1994) 77, 1101-1116.

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    Bob (Robert) ROBINSON

Bob obtained a BSc (1987) in Chemistry from King's College, London University, an MSc (1990) in Biochemistry from University of British Columbia, and a DPhil (1996) in Structural Biology from Oxford University. During his postdoctoral studies at the Salk Institute for Biological Studies (1996-2001), Bob solved the X-ray structure of Arp2/3, an actin-nucleating complex consisting of seven proteins. In 2001, Bob was appointed as a Senior Lecturer at Uppsala University. There, the research group elucidated structures of key actin-regulating proteins. Bob became an EMBO Young Investigator in 2003. Bob joined IMCB as a Principal Investigator in 2005 and became a Research Director in 2011. He holds adjunct/affiliated positions at NTU (LKCMedicine, NISB and SBS) and at NUS (Biochemistry and SynCTI), and serves on the Editorial Boards of Open Biology and Cytoskeleton. In Singapore, the laboratory has been instrumental in deciphering the evolutionary and structural bases of how force generated from polymerizing motors is integrated into biological processes. The laboratory runs the IMCB X-ray Facility.

    Structural Bases of Pathogenicity and Disease Laboratory

In plain English: The driving principle of the laboratory is that shape defines function. This laboratory uses structural biology to “see” the protein components of biological machines. Through understanding how the parts fit together, and how the components move relative to each other, we begin to understand what these biological machines do, and how and why they work. Specifically, we discover the shapes of key components of protein machines that are used by pathogens or are involved in the progression of human diseases. The laboratory is interested in all areas of aberrant protein function and misregulation, particularly in disease conditions arising from genetic mutations or external challenges, such as infection. One central theme of the laboratory is in understanding how force-generating protein machines are harnessed by biological processes, for instance during pathogen invasion.

The evolution of polymerizing protein machines. The “designs” of protein machines have been perfected (selected for) over several billion years of evolution. Through comparing the genomes from organisms that have diverged at different time points in evolution, we chart the paths of how protein machines have become more sophisticated in carrying out their functions. In this area, the laboratory has led the way in showing that the filament force generating machines from bacteria, plants and animals have followed different paths during evolution. In bacteria, there appears to be one-filament-one-function design, whereas in animals there is a universal-pool-of-actin that drives many processes.

Umesh treading the path of actin filament evolution from bacteria to animals. Read the details in Gunning et al., 2015.

Bacterial polymerizing protein machines. Many pathogenic bacteria encode their toxins and antibiotic resistance proteins on large DNA plasmids. During cell division, these plasmids need to be actively segregated to ensure the faithful inheritance of these pathogenic agents. Actin-like proteins are frequently employed as the force-generating motors used to separate pairs of plasmids prior to cell division. These proteins form filaments that elongate, which propel the plasmids attached to their tips into the daughter cells. Different plasmids have evolved varied designs of these force generating actin filaments. Presumably, they have become optimized for the size and cellular environment of each plasmid. The laboratory has made considerable progress in uncovering the unexpected and unusual designs of bacterial motor proteins. Two of the most significant discoveries are the actin (ParM) proteins from Bacillus thuringiensis (Jiang et al, 2016) and Clostridium tetani (Popp et al., 2012), which form remarkable antiparallel nanotubules and twisted filaments, respectively.

David and Shimin discover a novel actin motor from Bacillus thuringiensis that forms nanotubules. Read their findings in Jiang et al, 2016.

The universal-pool-of-actin in eukaryotes. Animals have adopted a universal-pool-of-actin to power movement in a vast range of biological processes, such as cell locomotion and phagocytosis. Thus, they use a common molecular machine to power many types of biological movement. The universal-pool-of-actin strategy requires the actin polymerization machine to be highly regulated to ensure that the actin pool is always maintained, no matter the demands of any single process. The laboratory has made significant discoveries in determining how the pool of actin monomers is maintained in an elevated state, how filament lengths are regulated by capping proteins, and how the force from actin polymerization is integrated into specific processes.

Albert conquers the structure of thymosin-β4 (rainbow) bound to an actin monomer (black/white). Read how this complex maintains the pool of actin monomers in Xue et al., 2014.

Subversion of human actin by pathogens. Since the actin filament has barely changed in the one billion years that separate humans and yeast, many pathogens have evolved to exploit or disable this force-generating machine. One such example is the bacterium Yersinia pestis, the cause of the bubonic plague, which has had a profound affect on the course of human civilization during outbreaks known as the Plague of Justinian and the Black Death. The laboratory has made a major advance in understanding how this pathogen evades the human immune system. From determining the shape of a complex between a protein from the pathogen (YopO) and actin, the laboratory has uncovered how this organism can turn off the process of phagocytosis, which otherwise would destroy the pathogen. The laboratory has an active program in studying other host-pathogen interactions.

Wei Lin contemplates how the Black Death agent, Yersinia pestis (pink), uses YopO (black) to disable actin (cyan) polymerization and turn off phagocytosis. Read her thoughts in Lee et al. 2015.

Exploiting our discoveries. Discoveries in basic science can occasionally be repurposed by humans to create new tools, reagents and potential drugs in a similar way that pathogens have hijacked the actin force-generating system (previous section). One such discovery comes from collaboration with the Manser laboratory, in which an artificial protein construct (iBox:PAK4) spontaneously forms crystals when expressed within mammalian cells. The quality of these crystals was sufficient to solve the structure inside an intact cell, from which we realized that it would be possible to include other proteins into the crystal scaffold created by iBox:PAK4. We are developing this in cellulo crystal system for many potential applications, such as cellular sensors, probes, drug:ligand interactions, drug development, and as a protein expression and purification matrix.

Read how he solved the structure within intact cells in” with “Read how he solved the structure of the iBox:PAK4 scaffold within intact cells in Baskaran et al. 2015.

A GFP hybrid crystal growing inside a living cell.

Techniques The laboratory specializes in a range of structural biology and biophysical techniques, which include: protein crystallography, electron microscopy, total internal reflection fluorescence (TIRF) microscopy, small angle X-ray scattering (SAXS), fluorescence, dynamic light scattering and mass spectrometry (in collaboration with Gunaratne and Sobota groups). These methods allow the determination of the conformations and dynamics of protein complexes and interactions, which provide understanding of how each protein performs, or fails to perform, in its biological function. We are also actively engaged in drug design and involved in structural biology method development.
The laboratory uses several synchrotron facilities including: Diamond, NSRRC, ESRF and ALS.

Collaborations, Students and Postdocs The laboratory collaborates extensively within Singapore and internationally. Singapore connections include joint projects with the A*STAR entities BioTrans, BII, ICES, and the p53lab, and with SynCTI, NUS and NTU, often supplementing programs within these organizations with structural biology expertise. The laboratory is keen to expand this portfolio particularly in establishing links with industry and clinical researchers. Similarly, we encourage applications from A*STAR scholars, returning scholars and prospective scholars, as well as from potential graduate students and postdocs that are either self-financed or willing and eligible to apply for one of the following schemes:




NTU Institute Structural Biology


Many thanks to Ciccy Wang and Ace Khong for help with the images and web pages.