The MRC HGU Genome Engineering Resource supports our ambition is to link genotype to phenotype, connecting genetic variation to dysfunction across scales to comprehensively interpret the human genome as a platform for better diagnosing and treating human disease. Image The MRC HGU Genome Engineering Resource (GER) supports multimodal research using advanced model systems. Our ambition at MRC HGU is to link genotype to phenotype, connecting genetic variation to dysfunction across scales to comprehensively interpret the human genome as a platform for better diagnosing and treating human disease. Expert technicians and technologists within the resource support the design, creation and analysis of genetically modified cellular, zebrafish and mouse models. Our central knowledge and management of mouse, zebrafish and cell models helps us plan, manage and reduce our overall use of animals and helps ensure consistent application of good research practice across research groups. Our internal expertise complements that at MRC Harwell and connects externally via local and national zebrafish collaborative networks and the MRC National Mouse Genetics Network. Genome Engineering Resource Goals Provision of excellent, accessible technical support and training on the design and use of animal and cell models across the HGU and beyond Provision of mouse and human ES cell culture manipulation within the Unit and creating an outward facing human ES resource Provision of expert specialist cell culture generation/ manipulation including neural stem cells, organoids and gastruloids Achieve consistency and value for money for key activities including cell culture, transgenic creation, animal use, genotyping and colony maintenance Provide technical expertise to perform regulated procedures on animals in compliance with Home Office regulations Image Mice: Provision of support (embryo transfer) to generate new transgenic and genome-edited mouse lines, and support colony management, tissue and embryo dissection, generation of primary cells. Determination and implementation of best genotyping strategy. Cells: Support and training for specialised cell work, including mouse ES engineering and culture, primary cell generation and culture, human ES cell expertise, large-scale screens Histology: Expert histology and histology training (all tissues) Phenotyping: Support and training for anatomic and functional (eye) phenotyping More specialist downstream analysis and phenotyping work lies within HGU groups but this team will ensure our other embedded expertise becomes more accessible for HGU and external research. Image Zebrafish: Routine care and feeding of fish. Scientific support for fish imaging, fluorescence screening, genotyping (adult and embryo), molecular biology, support for experiment and project planning and troubleshooting. Support and training for husbandry, cryopreservation, fish shipments, IVF, microinjection, electroporation, identification of F0s and breeding stable lines. We based our tank costing on the expected costs of staff, consumables and basic maintenance for 2023-2028. This gives a tank fee that has been shared with users: Tank cost per week (£) 2023 2024 2025 2026 2027 Medium 4.76 4.95 5.15 5.36 5.58 Large 7.14 7.43 7.72 8.04 8.37 Key achievements, outputs and added value Current and former core-funded GER staff have co-authored 21 MRC HGU scientific publications since 2018. The expertise of this team underpins and further links our Unit collaborative projects, for example the Hill, Lettice and Bickmore groups (Williamson et al.2019) and the Adams, Mill and Caceres (Haward et al., 2021). These examples below highlight some key achievements for our modelling expertise and technical team: Findlay AS, McKie L, Keighren M, …,Jackson IJ. (2020) Fam151b, the mouse homologue of C.elegans menorin gene, is essential for retinal function. Sci Rep. 10(1):437. Heyn P, … Kilanowski F, Sproul D, Jackson AP (2019) Gain-of-function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions. Nat Genet. 51(1): 96-105. Maslon MM, …,Kilanowski, F…, Adams IR, Cáceres JF (2019) A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes. EMBO J 38(9):e101244. Travnickova J, … Ponting CP, Patton EE.(2019) Zebrafish MITF-Low Melanoma Subtype Models Reveal Transcriptional Subclusters and MITF-Independent Residual Disease. Cancer Research 2019 Travnickova J….. Wyatt C, Patton EE. Fate mapping melanoma persister cells through regression and into recurrent disease in adult zebrafish. bioRxiv 2022 Williamson I..Devenney PS, …, Kilanowski F, Hill RE, Bickmore WA, Lettice LA. (2019) Developmentally regulated Shh expression is robust to TAD perturbations Development 146(19):dev179523 This article was published on 2024-09-23
