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  • 21 June 2011 to 31 March 2019
  • Awards: Infrastructure Awards

High content screening system (Operetta) provides an automated fluorescence microscope with high throughput ability for image acquisition and analysis that measures biological activity in single cells following treatment with agents such as compounds or siRNAs in multi-well plates. This generates unbiased information from cell images that can be used for purposes of drug discovery or functional genomics. This system was used successfully to develop several phenotypic cell-based assays relevant to cardiovascular disease such as smooth muscle cell phenotype switching assay, endothelial cell migration, monocyte-endothelia cell adhesion assay, endothelial tube formation assay and scar-in-a jar assay “fibrosis”. Phenotypic assays have been employed to evaluate biological hypotheses or to perform high throughput screens of drug/siRNA libraries in collaboration with High throughput facility in Target Discovery Institute (Oxford).

Publications linked to this award:

  1. Douglas G, Hale AB, Patel J, Chuaiphichai S, Al Haj Zen A, Rashbrook VS, Trelfa L, Crabtree MJ, McNeill E, Channon KM. Roles for Endothelial Cell and Macrophage Gch1 and Tetrahydrobiopterin in Atherosclerosis Progression. Cardiovasc Res. 2018 Mar 27. PMID: 29596571
  2. Hancock RL, Masson N, Dunne K, Flashman E, Kawamura A. The Activity of JmjC Histone Lysine Demethylase KDM4A is Highly Sensitive to Oxygen Concentrations. ACS Chem Biol. 2017 Apr 21;12(4):1011-1019.
  3. Irshad S, Bansal M, Guarnieri P, Davis H, Al Haj Zen A, Baran B, Pinna CMA, Rahman H, Biswas S, Bardella C, Jeffery R, Wang LM, East JE, Tomlinson I, Lewis A, Leedham SJ. Bone morphogenetic protein and Notch signalling crosstalk in poor-prognosis, mesenchymal-subtype colorectal cancer. J Pathol. 2017 Jun;242(2):178-192.
  4. Al Haj Zen A, Nawrot DA, Howarth A, Caporali A, Ebner D, Vernet A, Schneider JE, Bhattacharya S. The Retinoid Agonist Tazarotene Promotes Angiogenesis and Wound Healing. Mol Ther. 2016 Oct;24(10):1745-1759.
  5. Elkins JM, Fedele V, Szklarz M, Abdul Azeez KR, Salah E, Mikolajczyk J, Romanov S, Sepetov N, Huang XP, Roth BL, Al Haj Zen A, Fourches D, Muratov E, Tropsha A, Morris J, Teicher BA, Kunkel M, Polley E, Lackey KE, Atkinson FL, Overington JP, Bamborough P, Müller S, Price DJ, Willson TM, Drewry DH, Knapp S, Zuercher WJ. Comprehensive characterization of the Published Kinase Inhibitor Set. Nat Biotechnol. 2016 Jan;34(1):95-103.