Title: NIHR GOSH BRC
Funder: Department of Health and Social Care

Abstract: The NIHR Great Ormond Street BRC (GOSH BRC) proposes to build on the outstanding successes of the past nine years to become one of the most innovative paediatric experimental medicine centres in the world. University College London (UCL) was ranked first for research power in the 2014 Research Excellence Framework and first in the NIHR RAND analysis of highly-cited papers in clinical science. UCL Institute of Child Health (ICH)/GOSH occupies the leading role for research in childhood medicine (independent Reuters 2015 audit). ICH/GOSH ranked first by citation impact compared to the six other world-leading paediatric hospitals and second only to Boston Children s Hospital by percentage of highly cited papers. RAND ranked GOSH 12th in 2013 with clear upward trajectory driven by the BRC. GOSH BRC is the only BRC in England for Children, and has leveraged an impressive &pound;193M of additional external income: &pound;8.3 for each &pound;1 of BRC investment. Cross-institutional collaboration with other partners (Cambridge, Oxford, Birmingham) and national institutes (Farr, Crick, Sanger, and other BRCs), is a key to our success. Translational research, especially for rare diseases, is increasingly driven by advances in novel technologies that allow platform-based rational analysis and the development of more targeted and bespoke therapeutic options. Our key aims and strategy reflect these developments and are therefore geared towards accelerated delivery of innovation for the benefit of children (Figure 1): (1) The Gene, Stem, and Cellular Therapies Theme addresses the development and implementation of cell and gene therapies for inherited immunohaematological disease and childhood cancer, and the adoption of these platform technologies to areas of unmet need including skin, metabolic and neuromuscular disease. (2) The Genomics and Systems Medicine Theme is focused on rare disease gene discovery. It enables technology development for whole genome or cell-free DNA analysis and drives large data mining and implementation for rapid diagnosis. (3) The Novel Therapies and their Translation into Childhood Diseases Theme is the European hub for childhood early phase I and II clinical trials, responsible for the third highest patient recruitment among all NIHR BRCs in 2014/15. The unique features are successful trial design expertise for rare diseases, bespoke cell repository for novel therapy development, biomarker development and cutting-edge innovation in antisense therapy. (4) The Advanced Treatments for Structural Malformation and Tissue Damage Theme develops pioneering combinations of surgical- and cell-based tissue and organ repair including artificial tracheal or digestive tract transplant, skull remodelling, prevention of in-utero malformation, and cell-based repair of the retina. This Theme combines stem-cell-based neo-organ creation or repair with innovative surgical technology. The four Cross-cutting Themes will add value by ensuring: (1) the training of the next generation of translational scientists and allied professions in The BRC Experimental Medicine Academy; (2) augmentation of our already successful enterprise structure through the Translational Research and Enterprise Accelerator; (3) connection of our 19 Highly Specialised Services and ~200 Rare Disease Cohorts to the Themes and platform technologies; and (4) further transformation of our research hospital to accommodate CRF High-end Inpatient Trials.

Lay abstract: The NIHR Great Ormond Street BRC (GOSH BRC) proposes to build on the outstanding successes of the past nine years to become one of the most innovative paediatric experimental medicine centres in the world. University College London (UCL) was ranked first for research power in the 2014 Research Excellence Framework and first in the NIHR RAND analysis of highly-cited papers in clinical science. UCL Institute of Child Health (ICH)/GOSH occupies the leading role for research in childhood medicine (independent Reuters 2015 audit). ICH/GOSH ranked first by citation impact compared to the six other world-leading paediatric hospitals and second only to Boston Children s Hospital by percentage of highly cited papers. RAND ranked GOSH 12th in 2013 with clear upward trajectory driven by the BRC. GOSH BRC is the only BRC in England for Children, and has leveraged an impressive &pound;193M of additional external income: &pound;8.3 for each &pound;1 of BRC investment. Cross-institutional collaboration with other partners (Cambridge, Oxford, Birmingham) and national institutes (Farr, Crick, Sanger, and other BRCs), is a key to our success. Translational research, especially for rare diseases, is increasingly driven by advances in novel technologies that allow platform-based rational analysis and the development of more targeted and bespoke therapeutic options. Our key aims and strategy reflect these developments and are therefore geared towards accelerated delivery of innovation for the benefit of children (Figure 1): (1) The Gene, Stem, and Cellular Therapies Theme addresses the development and implementation of cell and gene therapies for inherited immunohaematological disease and childhood cancer, and the adoption of these platform technologies to areas of unmet need including skin, metabolic and neuromuscular disease. (2) The Genomics and Systems Medicine Theme is focused on rare disease gene discovery. It enables technology development for whole genome or cell-free DNA analysis and drives large data mining and implementation for rapid diagnosis. (3) The Novel Therapies and their Translation into Childhood Diseases Theme is the European hub for childhood early phase I and II clinical trials, responsible for the third highest patient recruitment among all NIHR BRCs in 2014/15. The unique features are successful trial design expertise for rare diseases, bespoke cell repository for novel therapy development, biomarker development and cutting-edge innovation in antisense therapy. (4) The Advanced Treatments for Structural Malformation and Tissue Damage Theme develops pioneering combinations of surgical- and cell-based tissue and organ repair including artificial tracheal or digestive tract transplant, skull remodelling, prevention of in-utero malformation, and cell-based repair of the retina. This Theme combines stem-cell-based neo-organ creation or repair with innovative surgical technology. The four Cross-cutting Themes will add value by ensuring: (1) the training of the next generation of translational scientists and allied professions in The BRC Experimental Medicine Academy; (2) augmentation of our already successful enterprise structure through the Translational Research and Enterprise Accelerator; (3) connection of our 19 Highly Specialised Services and ~200 Rare Disease Cohorts to the Themes and platform technologies; and (4) further transformation of our research hospital to accommodate CRF High-end Inpatient Trials.

Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: CANCER AND NEOPLASMS;INFLAMMATORY AND IMMUNE SYSTEM;GENERIC HEALTH RELEVANCE