个人简介
Dr. Round’s work has two themes, both rooted in the use of Atomic Force Microscopy (AFM) to solve complex problems in biomacromolecular science at the single molecule scale. His group works closely with Patrick Gunning and Andrew Kirby of the SPM group at IFR (http://www.ifr.ac.uk/spm).
The first theme is the development of an exciting new polymer sequencing tool, exploiting the properties of rotaxane complexes in order to form a sliding contact between molecule and transducer. For the first time, this will provide explicit information on the spatial relationships between multiple events observed in a single molecule pulling or unzipping experiments. The technique is finding applications in the fields of glycan epitope mapping and polymer sequencing. An introduction to this new technique is available here. Dr. Kate Bowman is the PDRA working on this BBSRC-funded project.
The second theme is unravelling the often complex and heterogeneous macromolecular systems formed by polysaccharides and glycoproteins. Key examples are the plant cell wall polysaccharide pectin and the mucin glycoproteins that make up the mucus barrier protecting the gastrointestinal, respiratory, ocular and cervicovaginal epithelia. Examples of how AFM has been key to unravelling details of the assembly, function and turnover of these systems are described here.
Other ongoing projects include Ben Rackham’s PhD project, an exploration of the mechanisms behind the bisintercalation of novel synthetic anticancer agents into DNA, and combining force spectroscopy with electrochemistry to study the electromechanical behaviour of redox proteins.
Dr. Round’s lab is equipped with a state of the art AFM, a JPK Nanowizard 3, capable of conventional and quantitative imaging and force spectroscopy in air and fluids, and a second AFM (Veeco/Bruker CP-II) for routine examination of samples in air.
Collaborators on NRP include at UEA: Mark Searcey (PHA) on drug bisintercalation; Julea Butt (CHE/BIO) on electron transfer in proteins; and Andrew Mayes (CHE) on polymer conjugation; at IFR: Patrick Gunning and Andrew Kirby in the SPM group; and Alan Mackie, Neil Rigby, Adam Macierzanka on the structure of mucin. External collaborators include Gudmund Skjåk-Bræk and Bjorn-Torge Stokke at NTNU, Trondheim, Norway on mapping and sequencing alginates. He is always happy to discuss how AFM methods can be applied to other exciting fields.
Dr. Round joined UEA in 2007 as an RCUK Academic Fellow in Pharmaceutical Nanosciences. His previous role was as Core Project postdoc for the IRC in Nanotechnology in the Physics department at the University of Bristol, following a postdoc at City University, New York. His PhD was awarded by UEA in 1999 and was carried out at the Institute of Food Research.
研究领域
This project exploits the recent development of a force-measuring microscope capable of, for the first time, mapping the distribution of defined oligomer sequences in single glycan polymers, by exploiting the phenomenon of rotaxanes - molecular rings threaded over a polymer chain. In this case, an atomic force microscope (AFM) probe picks up the ring (a cyclodextrin molecule) from its 'base' on a suitable polymer and slides it along and on to the glycan chain of interest, which is coupled to the rotaxane. Molecules known to recognise and bind to well-defined sequences within the polymer are allowed to interact with the polymer chain and form complexes; the ring is then passed along the chain and when it encounters a complex will 'unzip' it, removing the bound molecule. The mapping information comes from the magnitude of the force of interaction between the ring and each bound complex it encounters, along with the position along the chain at which the interaction occurs. By collecting this information from a large sample of individual polymers, a map of the distribution patterns of the known sequence is revealed. We have shown that this appealingly simple mechanical concept works for simple model polymers; now this project is designed to apply this entirely new sequencing tool to a medically and commercially highly significant glycan, alginate. Alginate gels form in the presence of calcium and other divalent cations due to the formation of so-called 'egg box' junction zones between aligned pairs of guluronic acid (oligoG) sequences. The minimum length of oligoG required to form a stable junction zone is not known and thus this project aims to determine both this minimum length and its distribution within well-characterised samples of alginate polymers.
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Bowman, K. A., Aarstad, O. A., Nakamura, M., Stokke, B. T., Skjåk-bræk, G., Round, A. N.(2016)Single molecule investigation of the onset and minimum size of the calcium-mediated junction zone in alginatein Carbohydrate Polymers148.pp. 52-60 Full Text UEA Repository(Article)
Sarcevica, I., Orola, L., Nartowski, K., Khimyak, Y., Round, A., Fabian, L.(2015)Mechanistic and kinetic insight into spontaneous cocrystallisation of isoniazid and benzoic acidin Molecular Pharmaceutics12.pp. 2981–2992 Full Text UEA Repository(Article)
Rackham, B. D., Howell, L. A., Round, A. N., Searcey, M.(2013)Non-covalent duplex to duplex crosslinking of DNA in solution revealed by single molecule force spectroscopyin Organic & Biomolecular Chemistry11.pp. 8340-8347 Full Text UEA Repository(Article)
Marin, M., Rackham, B. D., Round, A. N., Howell, L. A., Russell, D. A., Searcey, M.(2013)A rapid screen for molecules that form duplex to duplex crosslinks in DNAin Chemical Communications49.pp. 9113 Full Text UEA Repository(Article)
Round, A., Rigby, N., Garcia de la Torre, A., Macierzanka, A., Mills, E., Mackie, A.(2012)Lamellar Structures of MUC2-Rich Mucin: A Potential Role in Governing the Barrier and Lubricating Functions of Intestinal Mucusin Biomacromolecules13.pp. 3253-3261 Full Text UEA Repository(Article)
Mackie, A., Round, A., Rigby, N., Macierzanka, A.(2012)The Role of the Mucus Barrier in Digestionin Food Digestion3.pp. 8-15 Full Text UEA Repository(Article)
Meng, J., Levina, M., Rajabi-Siahboomi, A., Round, A., Reading, M., Craig, D.(2012)The Development of Thermal Nanoprobe Methods as a Means of Characterizing and Mapping Plasticizer Incorporation into Ethylcellulose Filmsin Pharmaceutical Research29.pp. 2128-2138 Full Text UEA Repository(Article)
Round, A., Rigby, N. M., MacDougall, A. J., Morris, V. J.(2010)A new view of pectin structure revealed by acid hydrolysis and atomic force microscopyin Carbohydrate Research345.pp. 487-497 Full Text UEA Repository(Article)
Dunlop, A., Wattoom, J., Hasan, E. A., Cosgrove, T., Round, A.(2008)Mapping the positions of beads on a string: dethreading rotaxanes by molecular force spectroscopyin Nanotechnology19.pp. 345706 Full Text UEA Repository(Article)
Hasan, E. A., Cosgrove, T., Round, A.(2008)Nanoscale Thin Film Ordering Produced by Channel Formation in the Inclusion Complex of α-Cyclodextrin with a Polyurethane Composed of Polyethylene Oxide and Hexamethylenein Macromolecules41.pp. 1393-1400 Full Text UEA Repository(Article)
Round, A. N., McMaster, T. J., Miles, M. J., Corfield, A. P., Berry, M.(2007)The isolated MUC5AC gene product from human ocular mucin displays intramolecular conformational heterogeneityin Glycobiology17.pp. 578-585 Full Text UEA Repository(Article)
Round, A. N., Berry, M., McMaster, T. J., Corfield, A. P., Miles, M. J.(2004)Glycopolymer charge density determines conformation in human ocular mucin gene products: an atomic force microscope studyin Journal of Structural Biology145.pp. 246-253 Full Text UEA Repository(Article)
Round, A. N., Miles, M. J.(2004)Exploring the consequences of attractive and repulsive interaction regimes in tapping mode atomic force microscopy of DNAin Nanotechnology15.pp. S176-S183 UEA Repository(Article)
Berry, M. S., McMaster, T. J., Round, A. N., Brayshaw, D. J.(2003)Mucin interactions in real timein Investigative Ophthalmology & Visual Science44. UEA Repository(Article)
Antognozzi, M., Szczelkun, M. D., Round, A. N., Miles, M. J.(2002)Comparison between shear force and tapping mode AFM - High resolution imaging of DNAin Single Molecules3.pp. 105-110 UEA Repository(Article)
Round, A. N., Berry, M., McMaster, T. J., Stoll, S., Gowers, D., Corfield, A. P., Miles, M. J.(2002)Heterogeneity and persistence length in human ocular mucinsin Biophysical Journal83.pp. 1661-1670 UEA Repository(Article)
Batteas, J. D., Round, A. N., Yan, B., Dang, S., Estephan, R., Stark, R. E.(2001)Nanomechanical studies of plant biopolymers by AFM and solid-state NMRin Abstracts of Papers of the American Chemical Society221.pp. 234-COLL UEA Repository(Article)
Humphris, A. D. L., Round, A. N., Miles, M. J.(2001)Enhanced imaging of DNA via active quality factor controlin Surface Science491.pp. 468-472 UEA Repository(Article)
Round, A. N., Rigby, N. M., MacDougall, A. J., Ring, S. G., Morris, V. J.(2001)Investigating the nature of branching in pectin by atomic force microscopy and carbohydrate analysisin Carbohydrate Research331.pp. 337-342 UEA Repository(Article)
Round, A. N., Yan, B., Dang, S., Estephan, R., Stark, R. E., Batteas, J. D.(2000)The influence of water on the nanomechanical behavior of the plant biopolyester cutin as studied by AFM and solid-state NMRin Biophysical Journal79.pp. 2761-2767 UEA Repository(Article)
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