My interests and that of the lab are in the cytoskeleton and particularly intermediate filaments (IFs) in astrocytes, cardiomyocytes and the eye lens. Our discovery of the functionally important interaction of the small heat shock protein (sHSP) chaperones with intermediate filaments led to the hypothesis that IFs are an essential part of the integrated stress response of cells. This interaction helps mediate/mitigate the biomechanical properties/responses of cells as these chaperones have been shown to be sensors of changes in the surface architecture of intermediate filaments. The sHSPs are also resident nuclear proteins, where in other animal systems they are involved in transcriptional control and in mammalian cells they are responsible for and subject to, amongst many other key cell biological regulators of life and death, TP53 stability. In the lens, the sHSPs and the intermediate filament cytoskeleton are critical to its optical and biomechanical properties of this remarkable tissue. The strong correlation between structure and function in the eye lens provides the platform for our current research interests to model lens cell organization in 5D. The membrane associations of selected intermediate filament proteins and their interaction with integral membrane proteins is a current interest. These studies help inform the mechanistic basis of how ionising radiation (IR) causes lens opacities and cataract. We predict that it is damage to the lens epithelial cells and disturbance to their patterns of cell proliferation and differentiation, but important questions remain. One hypothesis is that ionising radiation accelerates lens aging, but this does not explain the fomration of posterior subcapsular cataract that is often associated with IR-induced cataract. Given my eye lens interest, WG1 and the Biophysics of Cell and Tissue Structure is the best fit, but my expertise spans all four WGs and therefore I am keen to promote inter-WG collaboration.
Intermediate filament biochemistry, biophysics and cell biology; recombinant expression and purification; quality control of in vitro assembly. Pro- and eucarottic vectors for desmin, GFAP and some vimentin.
Protein chaperone resources, particularly concerning small heat shock proteins, alphaA- and alphaB-crystallins (HSPB4 and HSPB5), HSP27 (HSPB1), Pro- and eucarottic vectors, purification and structural characterisation; assays (in vitro/cell based/zebrafish) to assess intermediate filament and sHSP function.
Structure-function studies for procaryotic sHSPs.
imaging technologies (CLEM/SPIM/SIM); Stress biology; Synthetic biology; chaperone mechanism of action
Quinlan, RA., Schwartz, N., Windoffer, R., Richardson, C., Hawkins, T., Broussard, JA., Green, KJ. & Leube, R. (2017). A Rim and Spoke Hypothesis to explain the biomechanics roles for intermediate filament networks. Journal of Cell Science 130(20):3437-3445. doi: 10.1242/jcs.202168
Ismail VS, Mosely JA, Tapodi A, Quinlan RA, Sanderson JM. The lipidation profile of aquaporin-0 correlates with the acyl composition of phosphoethanolamine lipids in lens membranes. Biochim Biophys Acta. 2016 Jul 1. pii: S0005-2736(16)30234-6. doi: 10.1016/j.bbamem.2016.06.026. [Epub ahead of print] PMID: 27378310
Ricci M, Quinlan RA, Voïtchovsky K. Sub-nanometre mapping of the aquaporin-water interface using multifrequency atomic force microscopy. Soft Matter. 2016 Jul 4. [Epub ahead of print] PMID: 27373564
Quinlan RA. Drug Discovery. A new dawn for cataracts. Science. 2015 Nov 6;350(6261):636-7. doi: 10.1126/science.aad6303.PMID: 26542559
Wu JJ, Wu W, Tholozan FM, Saunter CD, Girkin JM, Quinlan RA.A dimensionless ordered pull-through model of the mammalian lens epithelium evidences scaling across species and explains the age-dependent changes in cell density in the human lens. J R Soc Interface. 2015 Jul 6;12(108):20150391. PMID: 26236824
Elliott JL, Der Perng M, Prescott AR, Jansen KA, Koenderink GH, Quinlan RA. The specificity of the interaction between αB-crystallin and desmin filaments and its impact on filament aggregation and cell viability. Philos Trans R Soc Lond B Biol Sci. 2013 Mar 25;368(1617):20120375. doi: 10.1098/rstb.2012.0375. Print 2013 May 5. PMID: 23530264