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School of Biological and Biomedical Sciences

Academic Staff

Prof R Quinlan, BSc hons; PhD


Researcher ID profile

Personal web page

Telephone: +44 (0) 191 33 41331
Fax: +44 191 334 1201

Contact Prof R Quinlan (email at r.a.quinlan@durham.ac.uk)

Biography

This image shows an epithelial cell that has been stained with antibodies to the small heat shock protein, HSP27.

Professor Roy Quinlan joined the University of Durham in 2001 and was one of those responsible for founding the Biophysical Sciences Institute, which was then established in 2007. He is a Biochemistry graduate and PhD from the University of Kent where he worked on microtubules with Professor Keith Gull FRS, before taking up an Alexander von Humboldt fellowship at the German Cancer Research Centre to work on Intermediate Filaments with Professor Werner Franke in 1981. He joined Dr Murray Stewart at the LMB Cambridge determining the coiled coil pitch of myosin LS2, but continued to investigate structural aspects of GFAP and lamins. In 1988, he was appointed as a lecturer to the Department of Biochemistry in Dundee. Here his interest in the cytoskeleton and particularly intermediate filaments in astrocytes, cardiomyocytes and the lens led to the discovery of the functionally important interaction of the small heat shock protein chaperones with intermediate filaments and its role in mediating the biomechanical properties of cells. In the lens, these proteins are key to its function as an optical element the eye. The strong correlation between structure and function in this tissue provides the platform for current research interests to model lens cell organization in 3 and 4 dimensions and integrating the cytoskeletal and chaperone functions into a scaled model of this tissue.

The eye lens is a tissue in which its cell structure and cell organisation is intimately linked to function.  The lens epithelium is a single layer of cells covering the anterior portion of the lens and underlying the anterior lens capsule. It is the cells of the lens epithelium that cause complications after cataract surgery and it is also those that  are damaged by ionising radiation and this damage then manifests itself as lens opacities and eventually cataract. The lens epithelial cells form the lens fibre cells by cell differentiation. This is restricted to those epithelial cells at the very equator of the lens. The lens grows, albeit slowly, throughout life. To ensure that there is a continual supply of lens epithelial cells to differentiate into fibre cells, a cell proliferation zone is adjacent to the lens equator. The geometrical order of the lens originates in the epithelium and is manifested in fibre cell differentiation. The differentiating lens fibre cells undergo massive (~1000X) elongation so that eventually the ends of these cells from opposing lens quadrants touch to form the lens sutures. This exemplifies the precise arrangement of the lens fibre cells required to produce a functional lens that is capable of refracting focused images onto the retina. The epithelial cells outside of the equatorial and proliferative zones have the potential to proliferate, but they appear quiescent. This is called the central zone. The epithelial cells retain the potential for proliferation and with funding from FIGHT FOR SIGHT, we are investigating the regenerative capacity of the lens as a mechanism to radically improve lens cataract surgery in the future.  We are also investigating how ionising radiation causes lens opacities and cataract. We predict that it is damage to the cells in the lens epithelium and disturbance to their patterns of cell proliferation and differentiation, but important questions remain. For instance: Are some cells more sensitive than others to (low dose) ionising radiation? Is there a threshold dose? How does radiation damage to the lens epithelium cause the posterior subcapsular cataract that is so typical of radiation damage to the lens? 

The mouse is an excellent animal model because of the wealth of genetic and molecular tools to dissect out the mechanistic detail of low dose radiation effects. The lens is very accessible and easy to dissect. My laboratory has developed flat mounting techniques and lens explant culturing techniques that has allowed us to link cell position in the epithelium to metric data (length, cross-sectional area; proliferation and apoptotic status). We can therefore detect the earliest signs of ionising radiation damage to the lens epithelium through changes in cell proliferation, cell death or cell metrics. Real time imaging of the developing eye lens would also be helpful to populate our knowledge base in terms of cell positioning, division planes and other organelle dynamics within the developing lens, but this is more easily achieved using zebrafish. With colleagues (Professor John Girkin and Dr Junjie Wu) in Durham University Biophysical Sciences Institute, we are using multidisciplinary approaches to reach this goal so that in future, mouse and zebrafish systems can complement each other.

Qu B, Landsbury A, Schönthaler HB, Dahm R, Liu Y, Clark JI, Prescott AR, Quinlan RA. Evolution of the vertebrate beaded filament protein, Bfsp2; comparing the in vitro assembly properties of a "tailed" zebrafish Bfsp2 to its "tailless" human orthologue. Exp Eye Res. 2012 Jan;94(1):192-202

Houck SA, Landsbury A, Clark JI, Quinlan RA. Multiple Sites in αB-Crystallin Modulate Its Interactions with Desmin Filaments Assembled In Vitro. PLoS One. 2011;6(11):e25859. Epub 2011 Nov 9.

Dahm R, van Marle J, Quinlan RA, Prescott AR, Vrensen GF. Homeostasis in the vertebrate lens: mechanisms of solute exchange. Philos Trans R Soc Lond B Biol Sci. 2011 Apr 27;366(1568):1265-77.

Sugiyama Y, Akimoto K, Robinson ML, Ohno S, Quinlan RA. A cell polarity protein aPKClambda is required for eye lens formation and growth. Dev Biol. 2009 Dec 15;336(2):246-56. Epub 2009 Oct 14.PMID: 19835853

Song S, Landsbury A, Dahm R, Liu Y, Zhang Q, Quinlan RA. <span >Functions of the intermediate filament cytoskeleton in the eye lens. J Clin Invest. 2009 Jul;119(7):1837-48. doi: 10.1172/JCI38277.

International Collaboration

  • Dr John I. Clark, Department of Biological Structure, University of washington, Seattle, Washington, USA
  • Dr Adrian Glasser, Professor of Optometry and Vision Sciences and Biomedical Engineering Benedict/Pitts Professor College of Optometry; University of Houston, Texas, USA
  • Dr Jer Kuszak, Emeritus Professor, University of Illinois, Chicago, USA
  • Professor Fei Sun, Professor, Structural Biology Institute of Biophysics Chinese Academy of Sciences, Beijing

Research Groups

Research Interests

  • Animal cell biology
  • Cataract and amyloidosis
  • Inherited human diseases caused by mutant cytoskeletal proteins, particularly cataract, cardiomyopathy and neuropathies
  • Motor neurone disease
  • Protein chaperones
  • The cytoskeleton
  • The eye lens and the ageing process

Selected Publications

Journal papers: academic

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