Andy Round

PhD Positions

Click here for current PhD opportunities in PHA. But feel free to email me to discuss projects outside these areas and alternative sources of funding.

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.

Selected Publications

Lamellar Structures of MUC2-Rich Mucin: A Potential Role in Governing the Barrier and Lubricating Functions of Intestinal Mucus
Round, AN, Rigby, NM, Garcia de la Torre, A, Macierzanka, A, Mills, ENC and Mackie, AR
Biomacromolecules, 2012, 13 (10). pp. 3253-3261. ISSN 1526-4602
DOI: 10.1021/bm301024x

A new view of pectin structure revealed by acid hydrolysis and atomic force microscopy
Round AN; Rigby NM; MacDougall AJ; Morris VJ
Carbohydrate Research 2010, 345, 487
DOI: 10.1016/j.carres.2009.12.019
(evaluated by Faculty of 1000: Rose J: "Deciphering the structures of plant cell wall polymers and the ways in which they interact..." of: [Round AN et al. A new view of pectin structure revealed by acid hydrolysis and atomic force microscopy. Carbohydr Res.2010 Feb 26; 345(4):487-97;
DOI: 10.1016/j.carres.2009.12.019]. Faculty of 1000, 08 Feb 2010. F1000.com/1836970#eval1378072)

Mapping the positions of beads on a string: dethreading rotaxanes by molecular force spectroscopy
Dunlop A; Wattoom J; Hasan EA; Cosgrove T; Round AN
Nanotechnology 2008, 19, 345706
DOI: 10.1088/0957-4484/19/34/345706

Nanoscale thin film ordering produced by channel formation in the inclusion complex of alpha-cyclodextrin with a polyurethane composed of polyethylene oxide and hexamethylene
Hasan EA; Cosgrove T; Round AN
Macromolecules 2008, 41, 1393
DOI: 10.1021/ma071484n
 

Single polymer mapping and sequencing: Function-based single molecule mapping of glycan monomers and motifs
(Funded by BBSRC)

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.

To date, we have shown that we can use an AFM probe to pick up a cyclodextrin ring threaded over a PEG polymer chain incorporating different aromatic groups, and that sliding the ring over those groups gives a measurable response in the force spectrum. We have shown that the spectra can be interpreted simply in terms of a steric interaction between ring and thread, opening the possibility of using this technique as a general method for sequencing linear polymers.



Figure 1: cartoon representation of sliding ring force spectroscopy: (a) sketch of expected force spectrum for a polymer with two bulky groups and (b) experimental data obtained on such a system. [Dunlop et al 2008 Nanotechnology 19:345706]



Figure 2: distribution of rupture points (forces and distances) for control (open circles), PEO with aromatic groups at 100 and 200nm (red circles) and PEO with aromatic groups at 100 and 150nm (yellow circles). Graph at bottom right is a comparison of expected vs. experimental rupture positions for aromatic groups in PEO. [Dunlop et al 2008 Nanotechnology 19:345706]

We are currently working on applying this technique to polysaccharides, which requires the development of a specific end-conjugation method for attaching a PEG chain to the reducing end of a polysaccharide.

Following the hydrolysis of pectin at the single molecule scale
Coming soon

MUC2 mucin in the porcine small intestine trimerises to form flat, weakly interacting lamellae
Coming soon

Novel anticancer agents that bisintercalate DNA – a single molecule view
Coming soon

Research Funding

Molecular Recognition of Polymer Microstructure
04/04-03/06 IRC Exploratory Project in collaboration with Prof. Terence Cosgrove (Chemistry Dept., University of Bristol)

I was awarded an IRC exploratory project in collaboration with Prof. Terence Cosgrove (Bristol, School of Chemistry), providing funding for a 2 year postdoctoral research assistant to assist in the development of a novel force spectroscopy-based single molecule sequencing technique exploiting the spontaneous self-assembly of pseudorotaxanes. This project laid the groundwork for the following grant proposal and defined the approach we are now taking. Two papers resulting from this work are currently in preparation.

The AFM Lasso'- a new analytical tool for single molecule sequencing
10/05-09/08 EPSRC/RSC Analytical Chemistry Trust Fund Analytical Science Studentships
in collaboration with Prof. Terence Cosgrove and Prof. Tony Davis (Chemistry Dept., University of Bristol)

3 PhD studentships were awarded (starting October 2005) for this project, with the aim of developing the novel sequencing technique mentioned above for application to the sequencing of DNA using specifically designed macrocycles to form DNA-rotaxanes. After a successful first year we have produced a proof of the principle behind this project.

Function-based single molecule mapping of glycan monomers and motifs
10/10-10/13 BBSRC
£320,372

Single Molecule Studies of Novel Bisintercalators for Pharmaceutical and Nanoscience Applications
07/10-06/13 UEA studentship award
in collaboration with Prof. Mark Searcey (PHA)
PhD studentship

Unravelling the Intricacies of Protein ‘Nanowires
10/09-09/12 UEA studentship award
in collaboration with Prof. Julea Butt (CHE/BIO) and Dr. Tom Clarke (BIO)
PhD studentship