Ewch i’r prif gynnwys
Dr Rob Young

Dr Rob Young

Research Fellow

School of Optometry and Vision Sciences

Research Overview

My research centres around the application of electron optical techniques, especially transmission and scanning electron microscopy, to investigate the ultrastructure of connective tissues. The overarching hypothesis for my work has been that composition and structure of tissue matrices define tissue function. In the past I have worked in the field of musculo-skeletal biology, investigating the fine structure of ligaments and cartilage, to try to understand the changes within these tissues in degradative diseases such as osteo- and rheumatoid arthritis. For the past ten years I have worked in collaboration with Professor Andrew Quantock focussing on ocular tissues, including cornea, sclera and trabecular meshwork. A range of tissues obtained from human eyes, through both local and international collaborations, have been investigated to characterise the nature of interactions between collagens and proteoglycans in health and disease.

Our studies have involved a number of cutting edge technologies for microscopy, both in relation to new preparation techniques for tissue preparation, for example using low temperature tissue preservation (high pressure freezing and freeze substitution), and novel instrumentation for image acquisition (serial block face 3View ® SEM). Throughout my career I have maintained a keen interest in new methodology for electron microscopy. I have applied specialised localisation methods employing specific antibody markers to identify minute differences in tissue components, proteoglycans, during development of the cornea in the embryo. These appear to be important for the maturation of a transparent matrix, itself essential for vision. The same tissue molecules are also involved in the pathogenesis of certain blinding conditions where enzyme deficiencies gives rise to opacities in the cornea, eventually requiring a corneal transplant for treatment.

Currently there is enormous interest in 3D imaging techniques, not only in diagnostic imaging such as with OCT, but also at the level of single cells and matrix macromolecules. These methods of electron tomography and, most recently, serial block face scanning electron microscopy are being used in our electron microscopy laboratory in the Structural Biophysics Research Group.

 

Teaching Overview

I currently assist with laboratory-based teaching of postgraduate research students and undergraduates carrying out final year research projects.

 

Selected Publications

Young, RD, Knupp, C, Pinali, C, Png, K MY, Ralphs, J R, Bushby, AJ, Starborg, T, Kadler, KE, Quantock AJ.  2014. Three-dimensional aspects of matrix assembly by cells in the developing cornea Proceedings of the National Academy of Sciences  111 (2) 687-692

Young, RD, Liskova, P, Pinali, C, Palka, BP, Palos, M, Jirsova, K, Hrdlickova, E, Tesarova, M, Elleder, M, Zeman, J, Meek, KM, Knupp, C and Quantock, AJ. 2011. Large Proteoglycan Complexes and Disturbed Collagen Architecture in the Corneal Extracellular Matrix of Mucopolysaccharidosis Type VII (Sly Syndrome). Investigative Ophthalmology & Visual Science  52 (9) 6720-6728.

Young, RD, Swamynathan, SK, Boote, C, Mann, M, Quantock, AJ,  Piatigorsky, J, Funderburgh, JL, Meek, KM. 2009. Stromal Edema in Klf4 Conditional Null Mouse Cornea Is Associated with Altered Collagen Fibril Organization and Reduced Proteoglycans. Investigative Ophthalmology & Visual Science  50 (9) 4155-4161

Young, RD, Akama, TO, Liskova, P, Ebenezer, ND, Allan, B, Kerr, B, Caterson, B, Fukuda, MN, Quantock, AJ. 2007. Differential immunogold localisation of sulphated and unsulphated keratan sulphate proteoglycans in normal and macular dystrophy cornea using sulphation motif-specific antibodies. Histochemistry and Cell Biology 127 (1), 115-120

Young, RD, Quantock, AJ, Sotozono, C, Koizumi, N, Kinoshita, S. 2006. Sulphation patterns of keratan sulphate proteoglycan in sclerocornea resemble cornea rather than sclera. British Journal of Ophthalmology 90 (3), 391-393

Educational and Professional Qualifications:

1977: PhD, Morphological & ultrastructural studies of the rat vibrissal follicle, University of Dundee
1969 -1972: BSc, Upper second class Honours, Zoology & Comparative Physiology,
Queen Mary College, University of London

Academic Positions:

2003 $acirc; present    Senior Research Associate, Structural Biophysics Group, School of Optometry & Vision Sciences, Cardiff University
2002 $acirc; 2003 Research Associate, Environmental Biochemistry Research Group, School of Biosciences, Cardiff University
1996 - 2001 Senior Research Fellow, Connective Tissue Biology Laboratories, School of Biosciences, Cardiff University
1991 - 1995 Research Fellow, Department of Ophthalmology, Bristol Eye Hospital, University of Bristol
1990 - 1991 Research Fellow, Muscle & Collagen Research Group, Department of Veterinary Medicine, University of Bristol, Langford
1988 - 1989 Senior Scientific Officer, AFRC Institute of Food Research, Langford, Bristol
1977 - 1988 Postdoctoral Research Scientist, Departments of Tissue Physiology and Electron Microscopy, Strangeways Research Laboratory, Cambridge

External Memberships:

2003 -  present: Member of the Association for Research in Vision and Ophthalmology (ARVO)
2004 $acirc; present: Member of Cardiff Institute for Tissue Engineering and Repair (CITER)
1981 $acirc; present: Member of the CryoMicroscopy Group
1978 $acirc; present: Member of the British Society for Matrix Biology (BSMB)
1977 - present: Fellow of the Royal MIcroscopical Society (RMS)

Awards:

Winner of Wellcome Trust Biomedical Image Award, 2006
Winner of 2 Wellcome Trust Biomedical Image Awards, 1999.

2019

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2011

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2008

2007

2006

2005

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2000

Current Research Projects

$acirc; Structural studies of cornea after freezing with a new prototype cryoprobe.
$acirc; 3D reconstruction of keratocytes and extracellular matrix in developing avian cornea by serial block face scanning electron microscopy to investigate corneal stromal development.
$acirc; Comparative ultrastructural investigation of the trabecular meshwork in normal and glaucomatous human eyes.
$acirc; Microscopical studies of corneal endothelial cells in Fuchs corneal endothelial dystrophy.

Legends for Figures

Regular arrangement of collagen fibrils in adjacent lamellae of the corneal stroma, viewed in ultrathin section by transmission electron microscopy. Bar, 1 µm.

Figure 1: Regular arrangement of collagen fibrils in adjacent lamellae of the corneal stroma, viewed in ultrathin section by transmission electron microscopy. Bar, 1 µm.

Stereo pair of tilted images from electron tomography of human sclera showing collagen fibrils (blue) and associated proteoglycans (orange). Bar, 200nm.

Figure 2: Stereo pair of tilted images from electron tomography of human sclera showing collagen fibrils (blue) and associated proteoglycans (orange). Bar, 200nm.

Collagen fibrils in corneal stroma viewed by transmission electron microscopy, are shown here running left to right in longitudinal section, and are associated with irregular branching proteoglycan molecules. Bar, 300nm.

Figure 3: Collagen fibrils in corneal stroma viewed by transmission electron microscopy, are shown here running left to right in longitudinal section, and are associated with irregular branching proteoglycan molecules. Bar, 300nm.

3D reconstructions from serial block face scanning electron microscopy of embryonic cornea: A. raw dataset showing collagen fibril bundles (cb) and keratopodial processes (arrows) of keratocytes (k). B. 3D reconstruction reveals close association between keratopodia (pink), and collagen fibril bundles (blue). C. Orthogonal orientation of keratopodia aligns with arrangement of collagen bundles (D). Bars. 500 nm, A; 1  µm, B,C,D.

Figure 4: 3D reconstructions from serial block face scanning electron microscopy of embryonic cornea: A. raw dataset showing collagen fibril bundles (cb) and keratopodial processes (arrows) of keratocytes (k). B. 3D reconstruction reveals close association between keratopodia (pink), and collagen fibril bundles (blue). C. Orthogonal orientation of keratopodia aligns with arrangement of collagen bundles (D). Bars. 500 nm, A; 1 µm, B,C,D.

 

Funding:

Quantock AJ (PI), K Meek & C Tucker: £836,976. A physical characterisation of assembly mechanisms and light transmission in the cornea.  EPSRC project grant. 2008 $acirc; 2011

Research Collaborators:

Professor Shigeru Kinoshita, Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Professor Noriko Koizumi, Centre for Regenerative Medicine, Department of Biomedical Engineering, Doshisha University, Kyoto, Japan:  A New Minimally Invasive Surgery for the Treatment of Corneal Endothelial Disease