![Carlo Knupp](https://profiles-cardiff.imgix.net/attachments/2842?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Overview
My main research interests range from visual fields to understanding the molecular organisation of fibrous proteins, in particular that of collagens forming networks and that of the proteins in the muscle sarcomere.
Perimetry is a powerful tool, in association with others, for the diagnosis and assessment of many eye conditions including maculopathies, optic neuropathies and intra-cranial lesions. I am particularly interested in the ocular toxicity of the anti-epileptic drug vigabatrin. Although an extremely effective drug at containing the symptoms of epilepsy, it is associated with irreversible visual field loss. In collaboration with Professor John Wild, I am developing a staging system to recognise and characterise vigabatrin associated visual field loss, which should prove fundamental in managing patients treated with the drug (https://www.ncbi.nlm.nih.gov/pubmed/31250314)
Network forming collagens do not form fibrils, but their general role appears to be to provide both mechanical strength and filtering properties. In some cases the open networks that they form are ordered enough that their structure can be analysed both by X-ray diffraction and by electron microscopy to reveal the basic molecular packing arrangements. I have taken advantage of the remarkably good order in the network-like structure of the egg case walls of the dogfish to reveal an open, body-centred, collagen molecular assembly. Intriguingly, something similar to this has been found in the human eye associated with a condition known as full thickness macular holes. In this case it appears to be collagen Type VI that is forming the aggregates. I am continuing to explore the nature of such collagen aggregates in the eye, especially in relation to Sorsbys Fundus Dystrophy and Age-Related Macular Degeneration. I also carry out theoretical analyses of collagen amino acid sequences to try to understand the general principles that link collagen structures and functions.
The cornea is another system where collagen is organised as a network that possesses incredible optical properties. My aim is to understand which physical mechanisms are responsible for this organisation and how corneal optical properties arise. At present we are pursuing this by means of three-dimensional electron microscopy.
In collaboration with the Cell Signalling and Cell Biology Section at the University of Bristol, I am studying the ultrastructure of the myosin and actin filaments using X-ray fibre diffraction. In particular, we are following dynamic molecular changes in active muscle by means of fast (millisecond) time-resolved X-ray diffraction using very powerful X-ray beams from synchrotron X-ray sources, particularly the Advance Photon Source, at Argonne National Laboratory, in the US.
Publication
2024
- Meek, K. M., Knupp, C., Lewis, P. N., Morgan, S. R. and Hayes, S. 2024. Structural control of corneal transparency, refractive power and dynamics. Eye (10.1038/s41433-024-02969-7)
2020
- Young, R. D. et al. 2020. Observations on nascent matrix structures in embryonic cornea: Important in cell interactions, or merely vestiges of the lens surface?. Archives of Clinical and Experimental Ophthalmology 2(2), pp. 67-72. (10.46439/ophthalmology.2.014)
2019
- Young, R. D. et al. 2019. Cell-independent matrix configuration in early corneal development. Experimental Eye Research 187, article number: 107772. (10.1016/j.exer.2019.107772)
- Knupp, C. and Squire, J. M. 2019. Myosin cross-bridge behaviour in contracting muscle- The T1 Curve of Huxley and Simmons (1971) revisited. International Journal of Molecular Sciences 20(19), article number: 4892. (10.3390/ijms20194892)
- Wild, J., Smith, P. E. M. and Knupp, C. 2019. Objective derivation of the morphology and staging of visual field loss associated with long-term vigabatrin therapy. CNS Drugs 33(8), pp. 817-829. (10.1007/s40263-019-00634-2)
- Burgoyne, T. et al. 2019. Three-dimensional structure of the basketweave Z-band in midshipman fish sonic muscle. Proceedings of the National Academy of Sciences 116(31), pp. 15534-15539. (10.1073/pnas.1902235116)
- Eakins, F., Knupp, C. and Squire, J. M. 2019. Monitoring the myosin crossbridge cycle in contracting muscle: steps towards 'Muscle-the Movie'. Journal of Muscle Research and Cell Motility 40(2), pp. 77-91. (10.1007/s10974-019-09543-9)
2016
- Eakins, F., Pinali, C., Gleeson, A., Knupp, C. and Squire, J. M. 2016. X-ray diffraction evidence for low force actin-attached and rigor-like cross-bridges in the contractile cycle. Biology 5(4), article number: 41. (10.3390/biology5040041)
- Kamma-Lorger, C. S. et al. 2016. Role of Decorin core protein in collagen organisation in Congenital Stromal Corneal Dystrophy (CSCD). PLoS ONE 11(2), article number: e0147948. (10.1371/journal.pone.0147948)
2015
- Meek, K. M. A. and Knupp, C. 2015. Corneal structure and transparency. Progress in Retinal and Eye Research 49, pp. 1-16. (10.1016/j.preteyeres.2015.07.001)
- Gardner, S. J., White, N., Albon, J., Knupp, C., Kamma-Lorger, C. S. and Meek, K. M. 2015. Measuring the refractive index of bovine corneal stromal cells using quantitative phase imaging. Biophysical Journal 109(8), pp. 1592-1599. (10.1016/j.bpj.2015.08.046)
2014
- Arkill, K. P. et al. 2014. Resolution of the three dimensional structure of components of the glomerular filtration barrier. BMC Nephrology 15, article number: 24. (10.1186/1471-2369-15-24)
- Young, R. D. et al. 2014. Three-dimensional aspects of matrix assembly by cells in the developing cornea. Proceedings of the National Academy of Sciences 111(2), pp. 687-692. (10.1073/pnas.1313561110)
2011
- Koudouna, E. et al. 2011. Preliminary electron microscopical studies of connective tissue in the human lamina cribrosa [Abstract]. International Journal of Experimental Pathology 92(6), pp. A26. (10.1111/j.1365-2613.2011.00780.x)
- Bushby, A. J., P'ng, K. M. Y., Young, R. D., Pinali, C., Knupp, C. and Quantock, A. J. 2011. Imaging three-dimensional tissue architectures by focused ion beam scanning electron microscopy. Nature Protocols 6(6), pp. 845-858. (10.1038/nprot.2011.332)
- Parfitt, G., Pinali, C., Akama, T. O., Young, R. D., Nishida, K., Quantock, A. J. and Knupp, C. 2011. Electron tomography reveals multiple self-association of chondroitin sulphate/dermatan sulphate proteoglycans in Chst5-null mouse corneas. Journal of Structural Biology 174(3), pp. 536-541. (10.1016/j.jsb.2011.03.015)
- Young, R. D. et al. 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), pp. 6720-6728. (10.1167/iovs.11-7377)
2010
- Parfitt, G. J., Pinali, C., Young, R. D., Quantock, A. J. and Knupp, C. 2010. Three-dimensional reconstruction of collagen-proteoglycan interactions in the mouse corneal stroma by electron tomography. Journal of Structural Biology 170(2), pp. 392-397. (10.1016/j.jsb.2010.01.019)
- Lewis, P., Pinali, C., Young, R. D., Meek, K. M. A., Quantock, A. J. and Knupp, C. 2010. Structural interactions between collagen and proteoglycans are elucidated by three-dimensional electron tomography of bovine cornea. Structure 18(2), pp. 239-245. (10.1016/j.str.2009.11.013)
- Kamma-Lorger, C. S. et al. 2010. Collagen and mature elastic fibre organisation as a function of depth in the human cornea and limbus. Journal of Structural Biology 169(3), pp. 424-430. (10.1016/j.jsb.2009.11.004)
2009
- Knupp, C., Offer, G., Ranatunga, K. W. and Squire, J. M. 2009. Probing muscle myosin motor action: X-Ray (M3 and M6) interference measurements report motor domain not lever arm movement. Journal of Molecular Biology 390(2), pp. 168-181. (10.1016/j.jmb.2009.04.047)
- Knupp, C., Pinali, C., Lewis, P., Parfitt, G. J., Young, R. D., Meek, K. M. A. and Quantock, A. J. 2009. The architecture of the cornea and structural basis of its transparency. In: McPherson, A. ed. Advances in Protein Chemistry and Structural Biology., Vol. 78. London: Academic Press, pp. 25-49., (10.1016/S1876-1623(08)78002-7)
2008
- Luther, P. K. et al. 2008. Understanding the organisation and role of Myosin binding protein C in normal striated muscle by comparison with MyBP-C knockout cardiac muscle. Journal of Molecular Biology 384(1), pp. 60-72. (10.1016/j.jmb.2008.09.013)
2006
- Knupp, C., Pinali, C., Munro, P. M., Gruber, H. E., Sherratt, M. J., Baldock, C. and Squire, J. M. 2006. Structural correlation between collagen VI microfibrils and collagen VI banded aggregates. Journal of Structural Biology 154(3), pp. 312-326. (10.1016/j.jsb.2006.03.023)
2003
- Squire, J. M., AL-Khayat, H. A., Harford, J. J., Hudson, L., Irving, T. C., Knupp, C. and Reedy, M. K. 2003. Modelling muscle motor conformations using low-angle X-ray diffraction. IEE Proceedings -Nanobiotechnology 150(3), pp. 103-110. (10.1049/ip-nbt:20031094)
- Squire, J. M. et al. 2003. New CCP13 software and the strategy behind further developments: stripping and modelling of fibre diffraction data. Fibre Diffraction Review 11, pp. 7-19.
- Squire, J. M., Knupp, C., AL-Khayat, H. A. and Harford, J. J. 2003. Millisecond time-resolved low-angle x-ray fibre diffraction: a powerful, high-sensitivity technique for modelling real-time movements in biological macromolecular assemblies. Fibre diffraction review 11, pp. 28-35.
2002
- Knupp, C., Amin, S. Z., Munro, P. M. G., Luthert, P. J. and Squire, J. M. 2002. Collagen VI assemblies in age-related macular degeneration. Journal of Structural Biology 139(3), pp. 181-189. (10.1016/S1047-8477(02)00534-8)
- Knupp, C., Chong, N. H. V., Munro, P. M. G., Luthert, P. J. and Squire, J. M. 2002. Analysis of the collagen VI assemblies associated with Sorsby's fundus dystrophy. Journal of Structural Biology 137(1-2), pp. 31-40. (10.1006/jsbi.2002.4449)
2001
- Knupp, C. and Squire, J. M. 2001. A new twist in the collagen story - the type VI segmented supercoil. Embo Journal 20(3), pp. 372-376. (10.1093/emboj/20.3.372)
Articles
- Meek, K. M., Knupp, C., Lewis, P. N., Morgan, S. R. and Hayes, S. 2024. Structural control of corneal transparency, refractive power and dynamics. Eye (10.1038/s41433-024-02969-7)
- Young, R. D. et al. 2020. Observations on nascent matrix structures in embryonic cornea: Important in cell interactions, or merely vestiges of the lens surface?. Archives of Clinical and Experimental Ophthalmology 2(2), pp. 67-72. (10.46439/ophthalmology.2.014)
- Young, R. D. et al. 2019. Cell-independent matrix configuration in early corneal development. Experimental Eye Research 187, article number: 107772. (10.1016/j.exer.2019.107772)
- Knupp, C. and Squire, J. M. 2019. Myosin cross-bridge behaviour in contracting muscle- The T1 Curve of Huxley and Simmons (1971) revisited. International Journal of Molecular Sciences 20(19), article number: 4892. (10.3390/ijms20194892)
- Wild, J., Smith, P. E. M. and Knupp, C. 2019. Objective derivation of the morphology and staging of visual field loss associated with long-term vigabatrin therapy. CNS Drugs 33(8), pp. 817-829. (10.1007/s40263-019-00634-2)
- Burgoyne, T. et al. 2019. Three-dimensional structure of the basketweave Z-band in midshipman fish sonic muscle. Proceedings of the National Academy of Sciences 116(31), pp. 15534-15539. (10.1073/pnas.1902235116)
- Eakins, F., Knupp, C. and Squire, J. M. 2019. Monitoring the myosin crossbridge cycle in contracting muscle: steps towards 'Muscle-the Movie'. Journal of Muscle Research and Cell Motility 40(2), pp. 77-91. (10.1007/s10974-019-09543-9)
- Eakins, F., Pinali, C., Gleeson, A., Knupp, C. and Squire, J. M. 2016. X-ray diffraction evidence for low force actin-attached and rigor-like cross-bridges in the contractile cycle. Biology 5(4), article number: 41. (10.3390/biology5040041)
- Kamma-Lorger, C. S. et al. 2016. Role of Decorin core protein in collagen organisation in Congenital Stromal Corneal Dystrophy (CSCD). PLoS ONE 11(2), article number: e0147948. (10.1371/journal.pone.0147948)
- Meek, K. M. A. and Knupp, C. 2015. Corneal structure and transparency. Progress in Retinal and Eye Research 49, pp. 1-16. (10.1016/j.preteyeres.2015.07.001)
- Gardner, S. J., White, N., Albon, J., Knupp, C., Kamma-Lorger, C. S. and Meek, K. M. 2015. Measuring the refractive index of bovine corneal stromal cells using quantitative phase imaging. Biophysical Journal 109(8), pp. 1592-1599. (10.1016/j.bpj.2015.08.046)
- Arkill, K. P. et al. 2014. Resolution of the three dimensional structure of components of the glomerular filtration barrier. BMC Nephrology 15, article number: 24. (10.1186/1471-2369-15-24)
- Young, R. D. et al. 2014. Three-dimensional aspects of matrix assembly by cells in the developing cornea. Proceedings of the National Academy of Sciences 111(2), pp. 687-692. (10.1073/pnas.1313561110)
- Koudouna, E. et al. 2011. Preliminary electron microscopical studies of connective tissue in the human lamina cribrosa [Abstract]. International Journal of Experimental Pathology 92(6), pp. A26. (10.1111/j.1365-2613.2011.00780.x)
- Bushby, A. J., P'ng, K. M. Y., Young, R. D., Pinali, C., Knupp, C. and Quantock, A. J. 2011. Imaging three-dimensional tissue architectures by focused ion beam scanning electron microscopy. Nature Protocols 6(6), pp. 845-858. (10.1038/nprot.2011.332)
- Parfitt, G., Pinali, C., Akama, T. O., Young, R. D., Nishida, K., Quantock, A. J. and Knupp, C. 2011. Electron tomography reveals multiple self-association of chondroitin sulphate/dermatan sulphate proteoglycans in Chst5-null mouse corneas. Journal of Structural Biology 174(3), pp. 536-541. (10.1016/j.jsb.2011.03.015)
- Young, R. D. et al. 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), pp. 6720-6728. (10.1167/iovs.11-7377)
- Parfitt, G. J., Pinali, C., Young, R. D., Quantock, A. J. and Knupp, C. 2010. Three-dimensional reconstruction of collagen-proteoglycan interactions in the mouse corneal stroma by electron tomography. Journal of Structural Biology 170(2), pp. 392-397. (10.1016/j.jsb.2010.01.019)
- Lewis, P., Pinali, C., Young, R. D., Meek, K. M. A., Quantock, A. J. and Knupp, C. 2010. Structural interactions between collagen and proteoglycans are elucidated by three-dimensional electron tomography of bovine cornea. Structure 18(2), pp. 239-245. (10.1016/j.str.2009.11.013)
- Kamma-Lorger, C. S. et al. 2010. Collagen and mature elastic fibre organisation as a function of depth in the human cornea and limbus. Journal of Structural Biology 169(3), pp. 424-430. (10.1016/j.jsb.2009.11.004)
- Knupp, C., Offer, G., Ranatunga, K. W. and Squire, J. M. 2009. Probing muscle myosin motor action: X-Ray (M3 and M6) interference measurements report motor domain not lever arm movement. Journal of Molecular Biology 390(2), pp. 168-181. (10.1016/j.jmb.2009.04.047)
- Luther, P. K. et al. 2008. Understanding the organisation and role of Myosin binding protein C in normal striated muscle by comparison with MyBP-C knockout cardiac muscle. Journal of Molecular Biology 384(1), pp. 60-72. (10.1016/j.jmb.2008.09.013)
- Knupp, C., Pinali, C., Munro, P. M., Gruber, H. E., Sherratt, M. J., Baldock, C. and Squire, J. M. 2006. Structural correlation between collagen VI microfibrils and collagen VI banded aggregates. Journal of Structural Biology 154(3), pp. 312-326. (10.1016/j.jsb.2006.03.023)
- Squire, J. M., AL-Khayat, H. A., Harford, J. J., Hudson, L., Irving, T. C., Knupp, C. and Reedy, M. K. 2003. Modelling muscle motor conformations using low-angle X-ray diffraction. IEE Proceedings -Nanobiotechnology 150(3), pp. 103-110. (10.1049/ip-nbt:20031094)
- Squire, J. M. et al. 2003. New CCP13 software and the strategy behind further developments: stripping and modelling of fibre diffraction data. Fibre Diffraction Review 11, pp. 7-19.
- Squire, J. M., Knupp, C., AL-Khayat, H. A. and Harford, J. J. 2003. Millisecond time-resolved low-angle x-ray fibre diffraction: a powerful, high-sensitivity technique for modelling real-time movements in biological macromolecular assemblies. Fibre diffraction review 11, pp. 28-35.
- Knupp, C., Amin, S. Z., Munro, P. M. G., Luthert, P. J. and Squire, J. M. 2002. Collagen VI assemblies in age-related macular degeneration. Journal of Structural Biology 139(3), pp. 181-189. (10.1016/S1047-8477(02)00534-8)
- Knupp, C., Chong, N. H. V., Munro, P. M. G., Luthert, P. J. and Squire, J. M. 2002. Analysis of the collagen VI assemblies associated with Sorsby's fundus dystrophy. Journal of Structural Biology 137(1-2), pp. 31-40. (10.1006/jsbi.2002.4449)
- Knupp, C. and Squire, J. M. 2001. A new twist in the collagen story - the type VI segmented supercoil. Embo Journal 20(3), pp. 372-376. (10.1093/emboj/20.3.372)
Book sections
- Knupp, C., Pinali, C., Lewis, P., Parfitt, G. J., Young, R. D., Meek, K. M. A. and Quantock, A. J. 2009. The architecture of the cornea and structural basis of its transparency. In: McPherson, A. ed. Advances in Protein Chemistry and Structural Biology., Vol. 78. London: Academic Press, pp. 25-49., (10.1016/S1876-1623(08)78002-7)
Research
Why are corneas transparent?
Mammalian corneas, like much of the extracellular matrix, are made essentially of collagen and proteoglycans. However, unlike the rest of the extracellular matrix, they are exquisitely transparent. To understand why we need first to understand how light interacts with each collagen fibril in the cornea.
https://sites.google.com/site/cornealtransparency/
References
Lewis PN, Pinali C, Young RD, Meek KM, Quantock AJ, Knupp C. (2010) Structural interactions between collagen and proteoglycans are elucidated by three-dimensional electron tomography of bovine cornea.
Structure. 18(2), 239-245.
Knupp C, Pinali C, Lewis PN, Parfitt GJ, Young RD, Meek KM, Quantock AJ (2010) The architecture of the cornea and structural basis of its transparency.
Advances in protein chemistry and structural biology,78, 25-49.