Partner 7: University College London (UCL), UK
The Proteomic and Metabolomic Research Facility at the UCL Institute of Child Health (ICH) & Great Ormond Street Hospital (GOSH) was created for both clinical and basic research for the diagnosis and elucidation of disease mechanisms in rare genetic diseases. This combined proteomic and metabolomic mass spectrometry facility provides a unique environment whereby both clinical and non-clinical researchers work side by side, using state-of-the-art technology, to study the pathogenesis of childhood and adult disease. Our focus is translational research and aims to establish rapid, sensitive methods to study, diagnose and monitor the treatment of patients.
Partner 7 team leader:
The ICH group will develop quality-controlled assays, in fully accredited laboratories, to proteomic/metabolomic profile humanised mice under development in WP8.1. These assays will include; 1) Creating proteomes of fibroblast/iPSC/liver/hepatocyte to (a) confirm transformation and quality control of transformation (b) Monitor global changes in secondary and downstream effects on protein expression due to the disease causing mutation. 2) Create high-throughput assays to confirm mutations in target proteins/metabolites and key factors identified in 1b, which can be used further to rapidly characterise tissues and the potential to monitor therapeutic intervention/drug discovery/toxicity experiments. 3) Create functional assays to monitor functionality of all transformed cells/animals by monitoring precursor/product reactions for e.g. incubating hepatocyte cell lines with deuterated cholesterol and monitor its incorporation into bile acids.
The facility is run under strict accredited conditions due to its close collaboration with GOSH and has over 25 years’ experience in assay method development and validation of complex assays. The facility is unique in that it can develop any diagnostic biomarker found in the proteomic wing of the facility into a rapid, multiplexed test in the metabolomic mass spectrometry section. The GOSH island site has the largest specialist enzyme laboratory in the UK and will be pivotal in any functional assay development. In addition, we are a key component in the EU IMI StemBanc initiative funded to develop quality control assays to monitor stem cell production, improve the efficiency of transformation and provide methods for high-throughput small molecule therapy screening. Thus, the UCL group has access to unique patient material, the expertise and equipment to create assays to monitor quality control, transformation and detect any secondary downstream changes due to the primary genetic defects.
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2. Heywood W, et al. (2012) Identification of new biomarkers for Down’s syndrome in maternal plasma. J Proteomics. May 17;75(9):2621-8.
3. Bennett K, et al. (2012) The identification of a new role for LEKTI in the skin: The use of protein ‘bait’ arrays to detect defective trafficking of dermcidin in the skin of patients with Netherton syndrome. J Proteomics. Jul 16;75(13):3925-37.
4. Sharma G, et al. (2012) Urinary conjugated α-tocopheronolactone – a biomarker of oxidative stress in children with type 1 diabetes. Free Radic Biol Med. Oct 26.
5. Bennett K, et al. (2010) A new role for LEKTI in skin barrier formation: Label-free quantitative proteomic identification of novel targets for the protease inhibitor LEKTI. J Proteome Res. 2010 Aug 6;9(8):4289-94.39.