Featured Publications

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	Characterizing Stable Protein Formulations	Wyatt Technology
	Sigrid Kuebler, "Characterizing Stable Protein Formulations", GEN 27, 20 Nov15 (2007).
Summary: This study demonstrated the use of DLS for the screening and characterization of proteins. This method performed rapid and automatic screening for aggregates present in protein formulation and required low sample volumes, as little as 10 µL per well. It is also possible to use this technology to perform automated temperature studies for stability screening.
GEN, Volume 27, Number 20 November 15, 2007

	Architecture of a Coat for the Nuclear Pore Membrane	Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller University
	Kuo-Chiang Hsia, Pete Stavropoulos, Günter Blobel, and André Hoelz, "Architecture of a Coat for the Nuclear Pore Membrane", Cell 131, 1313-1326 (2007).
Summary: The symmetric core of the nuclear pore complex can be considered schematically as a series of concentric cylinders. A peripheral cylinder coating the pore membrane contains the previously characterized, elongated heptamer that harbors Sec13-Nup145C in its middle section. Strikingly, Sec13-Nup145C crystallizes as a hetero-octamer in two space groups. Oligomerization of Sec13-Nup145C was confirmed biochemically. Importantly, the numerous interacting surfaces in the hetero-octamer are evolutionarily highly conserved, further underlining the physiological relevance of the oligomerization. The hetero-octamer forms a slightly curved, yet rigid rod of sufficient length to span the entire height of the proposed membrane-adjacent cylinder. In concordance with the dimensions and symmetry of the nuclear pore complex core, we suggest that the cylinder is constructed of four antiparallel rings, each ring being composed of eight heptamers arranged in a head-to-tail fashion. Our model proposes that the hetero-octamer would vertically traverse and connect the four stacked rings.
Cell, Volume 131, Pages 1313-1326

	Design and Testing for a Nontagged F1-V Fusion Protein as Vaccine Antigen against Bubonic and Pneumonic Plague	U.S. Army Medical Research Institute of Infectious Diseases
	B. S. Powell, G. P. Andrews, J. T. Enama, S. Jendrek, C. Bolt, P. Worsham, J. K. Pullen, W. Ribot, H. Hines, L. Smith, D. G. Heath, J. J. Adamovicz, "Design and testing for a nontagged F1-V fusion protein as vaccine antigen against bubonic and pneumonic plague", Biotechnology Progress 21(5), 1490-1510 (2005).
Summary: During discovery and testing of the F1-V fusion protein, proposed for development as the new plague vaccine antigen, the purified protein was observed to form soluble aggregates under certain conditions. Dr. Powell and colleagues used the DAWN EOS and Optilab to characterize the molecular structures of pure F1-V and its constituent subunits, the Yersinia pestis F1 and V proteins. Their investigation showed that aggregation was caused by the F1 subcomponent which forms soluble aggregates 10-times larger than the fusion protein under physiological temperature and salt. SEC-MALS studies also showed that the F1-V fusion protein structure is more stable to cold temperature, high salt, or reducing conditions than the individual subcomponent proteins.
Biotechnol. Prog., Volume 21, Pages 1490-1510

	Structure of nerve growth factor complexed with the shared neurotrophin receptor	Stanford University
	X.-L. He, K. C. Garcia, "Structure of nerve growth factor complexed with the shared neurotrophin receptor p75," Science 304 870-875 (2004).
Summary: The Garcia team at Stanford University put their DAWN instrument to work in order to help confirm that NGF homodimers and other NT dimers bind to only one neurotrophin receptor p75 in solution. In order to ensure that the 2:1 NGF/p75 stoichiometry isn't an artifact of crystallization, they measured the ligand:receptor stoichiometry and the assembly thermodynamics of p75 complexes in solution with NGF, NT-3, and NT-4/5. MALS and SEC of p75 alone revealed it to be a mixture of a higher and lower molar mass species determined dimer and monomer of 55.1 and 27.0 kDa respectively..
Science, Volume 304, Pages 870-875

	Oxidized mono-, di-, tri-, and polysaccharides as potential hemoglobin cross-linking reagents for the synthesis of high oxygen affinity artificial blood substitutes	University of Notre Dame
	J. H. Eike, A. F. Palmer, "Oxidized mono-, di-, tri-, and polysaccharides as potential hemoglobin cross-linking reagents for the synthesis of high oxygen affinity artificial blood substitutes," Biotechnol. Prog. 20 953-962 (2004).
Summary: Professor Palmer's team at the University of Notre Dame used their DAWN, Optilab and Eclipse systems to to measure the absolute molecular weight distribution of PolyHb dispersions in their study of oxidized mono/di/tri/poly saccharides as potential hemoglobin cross-linkers in order to produce oxygen carriers with high oxygen affinities and high molar masses.
Biotechnol. Prog., Volume 20, Pages 953-962

	An optical marker based on the UV-induced green-to-red photoconversion of a fluorescent protein	The Institute of Physical and Chemical Research (RIKEN)
	R. Ando, H. Hama, M. Yamamoto-Hino, H. Mizuno, A. Miyawaki, "An optical marker based on the UV-induced green-to-red photoconversion of a fluorescent protein," PNAS 99(20) 12651-12656 (2002)
Summary: The RIKEN group has cloned a fluorescent protein which emits green, yellow and red light, which they have named Kaede. The protein includes a tripeptide, His-Tyr-Gly. Various techniques used to test the transition from one color to another.The team used their DAWN instrument in conjunction with a Shodex HPLC system in order to characterize their Kaede protein. C-terminal His-tagged protein was found to have a mass of 115.0 kDa which is 4.33 times larger than that deduced from the primary structure of the protein. It was therefore concluded that Kaede forms a homotetrameric complex.
PNAS, Volume 99, Pages 12651-12656

	*Rational design of low-molecular weight heparins with improved in vivo* activity**	Massachusetts Institute of Technology
	M. Sundaram, Y. Qi, Z. Shriver, D. Liu, G. Zhao, G. Venkataraman, R. Langer, R. Sasisekharan, "Rational design of low-molecular weight heparins with improved in vivo activity," PNAS 100(2) 651-656 (2003).
Summary: Robert Langer's group at MIT demonstrates a practical analytical method enabling measurement of a structural correlate to in vivo anticoagulant function.They have used this information to to develop low-molecular weight heparins (LMWHs) with increased anticoagulant activity and decreased polydispersity. Desirable in vivo pharmacokinetic properties and the ability to cause release of tissue factor pathway inhibitor from the endothelium are among several beneficial aspects of these LMWHs. The findings demonstrate a simple approach for the creation of designer LMWHs. The group used their miniDAWN in conjunction with a Shodex HPLC system to determine the molar mass and polydispersity of their heparins.
PNAS, Volume 100, Pages 651-656

	Insights into the respiratory electron transfer pathway from the structure of nitrate reductase A	University of British Columbia
	M. G. Bertero, R. A. Rothery, M. Palak, C. Hou, D. Lim, F. Blasco, J. H. Weiner, N. C. J. Strynadka, "Insights into the respiratory electron transfer pathway from the structure of nitrate reductase A," Nature Structural Biology 10 681-687 (2003).
Summary: The team at the University of British Columbia has provided fundamental molecular details for understanding the mechanism of proton-motive force generation by a redox loop by studying the crystal structure of NarGHI at a resolution of 1.9 Angstroms. The group used their miniDAWN and Optilab DSP instruments to analyze the oligomerization of NarGHI in the presence of 0.7 mM Thesit.
Nature Structural Biology, Volume 10, Pages 681-683

	Chaperonin-mediated stabilization and ATP-triggered release of semiconductor nanoparticles	University of Tokyo
	D. Ishii, K. Kinbara, Y. Ishida, N. Ishii, M. Okochi, M. Yohda, T. Aida, "Chaperonin-mediated stabilization and ATP-triggered release of semiconductor nanoparticles," Nature 423 628-632 (2003).
Summary: The team at the University of Tokyo used their DAWN detector in conjunction with their Shodex HPLC system to find the molar mass of their T.th cpn/CdS nanoparticle inclusion complex. These results demostrate that T.th cpn within the protein-nanoparticle complex preserves its own structural identity, without formation of higher aggregates or dissociation into protein subunts. They further report that GroEL and T.th cpn can also enfold CdS semiconductor nanopartilces, giving them high thermal and chemical stability in aqueous media. Such biological mechanisms integrated into materials science may open a door to conceptually new bioresponsive devices. For information on specifics on their MALS data, please see the Supplementary Information for this publication.
Nature, Volume 423, Pages 628-632

	Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp 130 complex	Stanford University
	M. J. Boulanger, D.Chow, E. E. Brevnova, K. C. Garcia, "Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp 130 complex," Science 300 2101-2104 (2003).
Summary: Professor Garcia's group at Stanford characterized the structure and assembly of the immunoregulatory cytokine, interleukin-6 (IL-6), which activates a cell-surface signalling assembly. A structural model of the complex is presented. The complex forms a hexamer containing 2 IL-6, 2 IL6R-alpha and two gp 130 which assemble sequentially and cooperatively. This structure reveals a conserved architectural blueprint for assembly of all gp130-cytokine signalling complexes. For details on how the DAWN EOS was used, please see the Supporting Online Material for this paper.
Science, Volume 300, Pages 2101-2104

	Crystal structure of a tetradecameric assembly of the association domain of Ca²⁺/Calmodulin-dependent kinase II	Lawrence Berkeley National Laboratory
	A. Hoelz, A. C. Narin, J. Kuriyan, "Crystal strucutre of a tetradecameric assembly of the association domain of Ca²⁺/calmodulin-dependent kinase II," Molecular Cell 11 1241-1251 (2003).
Summary: The National Academy of Sciences team led by Professor Kuriyan used their DAWN EOS and Optilab instruments to confirm the crystal structure of the 143 residue association domain of Ca²⁺/Calmodulin-dependent kinase II (CaMKII). This association domain forms a hub-like assembly which is held together by extensive interfaces. The group has determined an atomic model for the hub and spoke architecture of the association domain, possibly the most complex of the hundreds of pritein kinases in animal cells. This architecture is a critical aspect of CaMKII's to respond to calcium signals and retain a molecular memory of activation events.
Molecular Cell, Volume 11, Pages 1241-1251

	An "endless" route to cyclic polymers	California Institute of Technology
	C. W. Bielawski, D. Benitez, R. H. Grubbs, "An 'endless' route to cyclic polymers," Science 297 2041-2044 (2002)
Summary: The team lead by Professor Robert Grubbs at Cal Tech developed a novel synthetic route in which the ends of growing polymer chains remain attached to a metal complex throughout the entire polymerization process, which eliminates the need for linear polymeric precursors and high dilution. A GPC system consisting DAWN EOS and Optilab detectors played crucial roles in providing strong physical evidence for circularity of the polymers synthesized. The DAWN EOS detector was used not only for molar mass determination, but also to found that the ratio of mean square radii of cyclic and linear polymers to be approximately 0.5 over a wide range of molar masses, as predicted by theory.
Science, Volume 297, Pages 2041-2044

	Structural evidence for feedback activation by Ras-GTP of the Ras-specific nucleotide exchange factor SOS	University of California at Berkeley
	S. M. Margarit, H. Sondermann, B. E. Hall, B. Nagar, A. Hoelz, M. Pirruccello, D. Bar-Sagi, J. Kuriyan, "Structural evidence for feedback activation by Ras-GTP of the Ras-specific nucleotide exchange factor SOS," Cell 112 685-695 (2003).
Summary: This National Academy of Sciences team led by Professor Kuriyan discovered a highly conserved Ras binding site on SOS. It is also shown that Ras-GTP forms ternary complexes with SOS^cat in solution. A DAWN EOS and an Optilab were used extensively to characterize their purified SOS complexes as well as verify the theoretically calculated values. Their research indicates the existence of a positive feedback mechanism for the spatial and temporal regulation of Ras.
Cell, Volume 112, Pages 685-695

	Light Scattering to Detect Compound Aggregation in Screening Assays	Wyatt Technology
	Dr. Bingyi Yao, Bob Collins, Dr. Michelle Chen "Light scattering to detect compound aggregation in screening assays," DPI 4,1 +32-2-240-26-11.
Summary: During the high-throughput screening of compound libraries, false positive results can be generated because some compounds form aggregates that nonspecifically inhibit receptors. These compound aggregates are readily detectable by optical methods such as light scattering. This article describes a system that measures dynamic light scattering, using the same conditions as for HTS, allowing the identification of false positives very early in the screening process.
Drug Plus International, Volume 4, Number 1, Pages 21-24

	Characterization of Hyaluronic Acid with On-Line Differential Viscometry, Multiangle Light Scattering, and Differential Refractometry	Wyatt Technology
	Jason Waters, Danielle Leiske, "Characterization of Hyaluronic Acid with On-Line Differential Viscometry, Multiangle Light Scattering, and Differential Refractometry," LCGC 23,3 (732) 225-9500.
Summary: Wyatt Technology in collaboration with Professor Skip Rochefort's group at Oregon State University used a DAWN EOS, an Optilab rEX and a ViscoStar to measure the intrinsic viscosity and Mark-Houwink-Sakurada (MHS) behavior of Hyaluronic Acid (HA). Unusual MHS behavior was demonstrated, perhaps helping explain the large variation in HA MHS coeffiecents that have been reported in the literature.
LGCG, Volume 23, Number 3, Pages 302-310