Dr Monica Berry

Dr Monica Berry

 

Nanophysics and Soft Matter Group (previously Clinical Sciences, Bristol Eye Hospital)

I am interested in long, sugar-rich, chatty molecules (mucins) and their interaction with other molecules and cells. Recent work has focused on the sugar groups at the surface of a gel, which modulate bacterial and immune cell binding to that surface.

 

Research keywords: AFM, glycobiology, mucins, nanoparticles, ocular surface, saliva, toxicology in vitro

 

Send Monica an email

Tel. No.: +44 (0)117 39 40014


 

Featured research: Mucins |  Toxicology in vitro

A short introduction to mucins

A soft mucus gel coats and protects the surfaces of wet epithelia where the body encounters its environment: the surfaces of eye, mouth, nose, respiratory and digestive systems, and more. Mucins, very large molecules whose peptide core is richly decorated with sugars, form the backbone of these mucus gels, where they interact with bacteria and viruses on the one hand, and with epithelial cells and cells of the immune system on the other.

mucin imaged by AFM

Secreted ocular mucin imaged in HEPES buffer with NiCl2 by AFM (TJ McMaster).

The higher regions of the molecule (here darker blue) are regions of high glycosylation, and at most 1.5 nm above the mica substrate.

Along the peptide core, sugars chains are very dense in places, and sparse in others, giving a mucin the appearance of a necklace of pearls (as shown, left, for a more than 5 µm long human ocular mucin molecule imaged by Atomic Force Microscopy). Epithelial mucins come in two flavours, secreted (like the example, left), and cell surface bound. The mucin subunit of the latter (below, right) is cleaved into the overlying fluid. Mucins spanning the cell membrane convey information to the inside of the cell.

MUC4 mucins imaged by AFM

Muc4 (gift from Kermit Carraway) on graphite, imaged in HEPES buffer with NiCl2 and 0.01% Tween 20, by AFM (D Brayshaw).

Changes in mucins are associated with disease in some organs e.g. breast and colon – MUC1, the first mucin discovered, has been the focus of research for its connection with breast cancer. In very severe dry eyes there is a decrease in goblet cells, cells which synthesise, store and secrete MUC5AC.

Sugar chains, in particular the last or last few sugars in the chain, are what a microorganism sees on a mucin molecule or gel: bacteria and viruses are very choosy in their sweet epitopes. An alteration in the charge or type of sugars can have a large effect on the resident microflora.

The general structure of mucins is conserved throughout the body, yet details are tuned to the site of secretion. For example, gastric mucins have long oligosaccharide chains, while at the ocular surface sugar chains are short.

The lynch-pin of my research has been understanding how the behaviour of molecules in a complex fluid is affected by alterations in their biophysical and biochemical characteristics. The complexity of molecular behaviour has prompted collaborations with other mucineers, especially Tony Corfield, physicists(1 & 2), (sugar) biochemists(3, 4, & 5), microbiologists(6), optometrists(7), and clinicians(8, 9, & 10).

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Toxicology in vitro

Corneal cross section

Organ-cultured cornea (left) and 3D corneal model (right) where epithelial cells grown on a collagen gel seeded with human corneal fibroblasts.

Marcus Radburn Smith and Berry (unpublished results)

 

 

A collaboration with the cosmetics industry on alternative methods for toxicity testing, has resulted in the development of a three-dimensional corneal model. Further to classical toxicology assays we characterised the cytokine secretion of the construct which was stable in controls and specifically altered after exposure to toxicants.

An newer interest is models to study nanoparticle toxicity in the light of their potential as a research tool and therapeutic modality.

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Author Title Year Journal/Proceedings/Books DOI/URL
Verey, F., Nexo, E., Greenwood, R., Berry, M. & Corfield, A.P. Trefoil factor family peptides are increased in the saliva of children with mucositis 2011 Clinical Chemistry and Laboratory Medicine
In Press
Berry, M. Ocular Mucins
in Encyclopaedia of the Eye
2010 184-193
Corfield, A. & Berry, M. Mucin Biophysics
in Encyclopaedia of Biophysics
2010 -
Haward, S.J., Odell, J.A., Berry, M. & Hall, T. Extensional rheology of human saliva 2010 Rheologica Acta
Suppl.
DOI URL
Baos, S., Berry, M., Heard, P., Brayshaw, D. & McMaster, T.J. Functional Mapping of Single Molecules and Gels using Atomic Force Microscopy 2009 Biophysical Journal
96(3), 644a
DOI URL 
Berry, M., Pult, H., Purslow, C. & Murphy, P.J. Mucins and Ocular Signs in Symptomatic and Asymptomatic Contact Lens Wear 2008 Optometry and Vision Science
85(10), 930-938 
Pult, H., Purslow, C., Berry, M. & Murphy, P.J. Clinical tests for successful contact lens wear: their relations and predictability 2008 Optometry and Vision Science
85(10), E924-E929 
DOI URL 
Royle, L., Matthews, E., Corfield, A., Berry, M., Rudd, P.M., Dwek, R.A. & Carrington, S.D. Glycan structures of ocular surface mucins in man, rabbit and dog display species differences 2008 Glycoconjugate Journal
25(8), 763-773 
DOI  
Round, A.N., McMaster, T.J., Miles, M.J., Corfield, A.P. & Berry, M. The isolated MUC5AC gene product from human ocular mucin displays intramolecular conformational heterogeneity 2007 Glycobiology
17(6), 578-585 
DOI  
Berry, M. & Radburn-Smith, M. Ocular toxicology in vitro - cell based assays 2006 Altex
23, 313-317
Paulsen, F. & Berry, M. Mucins and TFF peptides of the tear film and lacrimal apparatus 2006 Progress in Histochemistry and Cytochemistry
41(1), 1-53 
DOI URL 
Berry, M. & Ellingham, R. Mucins on the ocular surface
in Immunology of the lacrimal gland, tear film and ocular surface
2005 79-96
Brayshaw, D., Berry, M. & McMaster, T. Dynamic molecular resolution imaging and nanomechanical measurements of glycoprotein gels 2005 Biophysical Journal
88(1, Part 2 Suppl. S), 156A 
Roberton, A., Wiggins, R., Horner, P., Greenwood, R., Crowley, T., Fernandes, A., Berry, M. & Corfield, A. Novel bacterial mucinase, glycosulfatase, is associated with bacterial vaginosis 2005 Journal of Clinical Microbiology
43(11), 5504-5508 
DOI  
Schafer, G., Hoffmann, W., Berry, M. & Paulsen, F. Lacrimal gland-associated mucins. Age related production ancl their role in the pathophysiology of dry eye 2005 Ophthalmologe
102(2), 175-183 
Aknin, M., Berry, M., Dick, A. & Khan-Lim, D. Normal but not altered mucins activate neutrophils 2004 Cell and Tissue Research
318(3), 545-551 
DOI  
Berry, M., Brayshaw, D. & McMaster, T. Dynamic molecular resolution imaging of preocular fluid impressions 2004 British Journal of Ophthalmology
88(11), 1460-1466 
DOI  
Berry, M., Ellingham, R. & Corfield, A. Human preocular mucins reflect changes in surface physiology 2004 British Journal of Ophthalmology
88(3), 377-383 
DOI  
Berry, M. & Radburn-Smith, M. Conjunctiva organ and cell culture 2004 Methods in Molecular Medicine
107, 325-342
DOI URL 
Brayshaw, D., Berry, M. & McMaster, T. Single molecule chemical reactions and adsorption processes observed directly with AFM 2004 Biophysical Journal
86(1, Part 2 Suppl. S), 155A 
Brayshaw, D., Berry, M. & McMaster, T. Molecular adsorption: early stage surface exploration 2004 Ultramicroscopy
100(3-4), 145-151 
DOI  
Brayshaw, D., Berry, M. & McMaster, T. Reducing a polymer to its subunits as an aid to molecular mapping 2004 Nanotechnology
15(11), 1391-1396 
DOI  
Khan-Lim, D. & Berry, M. Still confused about rose Bengal? 2004 Current Eye Research
29(4-5), 311-317 
DOI  
McMaster, T., Brayshaw, D. & Berry, M. Unravelling glycoprotein-peptide interactions that influence mucus viscosity 2004 Biophysical Journal
86(1, Part 2 Suppl. S), 152A-153A 
Paulsen, F., Corfield, A., Hinz, M., Hoffmann, W., Schaudig, U., Thale, A. & Berry, M. Tear outflow. Impact of mucins and TFF peptides 2004 Ophthalmologe
101(1), 19-24 
DOI  
Paulsen, F., Langer, G., Hoffmann, W. & Berry, M. Human lacrimal gland mucins 2004 Cell and Tissue Research
316(2), 167-177 
DOI  
Round, A., Berry, M., McMaster, T., Corfield, A. & Miles, M. Glycopolymer charge density determines conformation in human ocular mucin gene products: an atomic force microscope study 2004 Journal of Structural Biology
145(3), 246-253 
DOI  
Aknin, M., Khan-Lim, D., Dick, A. & Berry, M. Mucins recruit leucocytes selectively 2003 Investigative Ophthalmology & Visual Science
44(Suppl. 1), 2503 
Berry, M., Harris, A. & Corfield, A. Patterns of mucin adherence to contact lenses 2003 Investigative Ophthalmology & Visual Science
44(2), 567-572 
DOI  
Brayshaw, D., Berry, M. & McMaster, T. Optimisation of sample preparation methods for air imaging of ocular mucins by AFM 2003 Ultramicroscopy
97(1-4), 289-296 
DOI  
Khan-Lim, D. & Berry, M. Still confused about Rose Bengal? 2003 Investigative Ophthalmology & Visual Science
44(Suppl. 1), 2455 
Paulsen, F., Corfield, A., Hinz, M., Hoffmann, W., Schaudig, U., Thale, A. & Berry, M. Characterization of mucins in human lacrimal sac and nasolacrimal duct 2003 Investigative Ophthalmology & Visual Science
44(5), 1807-1813 
DOI  
Berry, M., Corfield, A., Harris, A. & Lim, D. Functional processing of ocular mucins 2002
Lacrimal gland, tear film, and dry eye syndromes 3: basic science and clinical relevance, Pts A & B
506, 283-288 
Berry, M., Harris, A., Lumb, R. & Powell, K. Commensal ocular bacteria degrade mucins 2002 British Journal of Ophthalmology
86(12), 1412-1416 
Paulsen, F., Corfield, A., Gebhardt, M., Steven, P., Schaudig, U., Thale, A. & Berry, M. Distribution of mucins in human nasolacrimal ducts 2002 Investigative Ophthalmology & Visual Science
43(Suppl. 1), 899 
Round, A., Berry, M., McMaster, T., Stoll, S., Gowers, D., Corfield, A. & Miles, M. Heterogeneity and persistence length in human ocular mucins 2002 Biophysical Journal
83(3), 1661-1670 
Berry, M., McMaster, T., Corfield, A. & Miles, M. Exploring the molecular adhesion of ocular mucins 2001 Biomacromolecules
2(2), 498-503 
DOI  
Berry, M. & Jeffreys, D. Ocular injuries from household chemicals: Early signs as predictors of recovery 2001 In Vitro Molecular Toxicology
14(1), 5-13
DOI URL
Khan-Lim, D., Shankar, S. & Berry, M. Variation of mucins in dry eyes. 2001 Investigative Ophthalmology & Visual Science
42(4, Suppl. S), 188 
Berry, M., Ellingham, R. & Corfield, A. Membrane-associated mucins in normal human conjunctiva 2000 Investigative Ophthalmology & Visual Science
41(2), pp. 398-403 
URL
Ellingham, R., Berry, M. & Corfield, A. MUC2 and MUC5AC post-secretory mucins in normal and pathological pre-ocular gel. 2000 Investigative Ophthalmology & Visual Science
41(4, Suppl. S), 1443B818 
Khan-Lim, D., Berry, M. & Corfield, A. Stimulated and unstimulated normal tears dissolve different mucin populations. 2000 Investigative Ophthalmology & Visual Science
41(4, Suppl. S), 353B353 
Berry, M., McMaster, T., Corfield, A. & Miles, M. Ocular mucins form slender and long polymers: An atomic force microscopy study 1999 Investigative Ophthalmology & Visual Science
40(4), 5090 
Berry, M. Eye irritation: a view from beyond the cosmetics industry
in Alternatives to Animal Testing II
1999 -
Ellingham, R., Berry, M., Stevenson, D. & Corfield, A. Secreted human conjunctival mucus contains MUC5AC glycoforms 1999 Glycobiology
9(11), 1181-1189 
McMaster, T., Berry, M., Corfield, A. & Miles, M. Atomic force microscopy of the submolecular architecture of hydrated ocular mucins 1999 Biophysical Journal
77(1), 533-541 
Berry, M., Pastis, W., Ellingham, R., Frost, L., Corfield, A. & Easty, D. Hyaluronan in dry eye and contact lens wearers 1998
Lacrimal Gland, Tear Film, and Dry Eye Syndromes 2 - Basic Science and Clinical Relevance,
438, 785-790 
Berry, M., Ellingham, R. & Corfield, A. Membrane associated mucins in human conjunctiva 1997 Investigative Ophthalmology & Visual Science
38(4, Part 1), 751 
Berry, M., Ellingham, R. & Corfield, A. Physico-chemical characteristics of human ocular mucins 1997 Investigative Ophthalmology & Visual Science
38(4, Part 1), 2169 
Corfield, A., Carrington, S., Hicks, S., Berry, M. & Ellingham, R. Ocular mucins: Purification, metabolism and functions 1997 Progress in Retinal and Eye Research
16(4), 627-656 
Berry, M. & Easty, D. The effect of 0.1% sodium hyaluronate on human corneal epithelial cells 1996 Investigative Ophthalmology & Visual Science
37(3), 370 
Berry, M., Ellingham, R. & Corfield, A. Polydispersity of normal human conjunctival mucins 1996 Investigative Ophthalmology & Visual Science
37(13), 2559-2571 
URL
Berry, M., Ellingham, R. & Corfield, A. Conjunctiva: Organ and Cell Culture
in Human cell culture protocols
1996 503-517
Ellingham, R., Berry, M. & Corfield, A. Agarose gel electrophoresis of human tears: Mucin detected. 1996 Investigative Ophthalmology & Visual Science
37(3), 3902 
Berry, M., Gurung, A. & Easty, D. Toxicity of antibiotics and antifungals on cultured human corneal cells - effect of mixing, exposure and concentration 1995 Eye
9(Part 1), 110-115 
Berry, M., Corfield, A. & Easty, D. Partial characterization of human ocular mucins 1994 Investigative Ophthalmology & Visual Science
35(4), 1795 
Berry, M., Easty, D. & Declercq, E. Effect of antivirals on human corneal cells in-vitro 1994 Toxicology in Vitro
8(4), 727-729 
Frescura, M., Berry, M., Corfield, A., Carrington, S & Easty, D. Evidence of hyaluronan in human tears and secretions of conjunctival cultures 1994 Biochemical Society Transactions
22(2), S228 
Berry, M. & Easty, D. Isolated human and rabbit eye - models of corneal toxicity 1993 Toxicology in Vitro
7(4), 461-464 
Berry, M., Easty, D. & Declercq, E. Effects of antivirals on wound closure in vitro 1993 Investigations in Ophthalmology & Visual Science
34(4), 1320 
Larkin, D.F., Berry, M. & Easty, D. In vitro corneal pathogenicity of Acanthamoeba 1991 Eye
5(5), 560-568
DOI URL 

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