Timeline of innovation in avian genetic modification
The Roslin Institute and researchers working within the NARF have pioneered approaches to modify avian genomes
Poultry research at The Roslin Institute traces its origins to the establishment of the Institute of Animal Genetics by the University of Edinburgh in 1919, from which the Poultry Research Centre was formed in 1947 with support from the Agricultural Research Council. Research in this Centre merged into the Institute of Animal Physiology and Genetics Research in 1985, joined by the Animal Breeding Research Organisation, and this, in turn, became The Roslin Institute in 1993, funded directly by the Biotechnology and Biological Sciences Research Council (BBSRC). The Roslin Institute joined the University of Edinburgh in 2008. In 2013 the National Avian Research Facility opened at the Roslin Institute, funded jointly by the BBSRC and University of Edinburgh.
Roslin has pioneered approaches to modify the chicken genome
The first ever culture system for the fertilised ovum of chickens is developed at the Poultry Research Centre1. This paves the way for advances in the modification of the chicken genome, in 1994 by microinjection of foreign DNA into fertilised ova2 and later using lentiviral vectors to efficiently insert foreign genes3. This method allowed the introduction of novel, cloned genes into the chicken genome, and was utilised in a wide range of projects.
This technology is exploited to produce transgenic hens, which carry new, artificial genes, enabling them to make valuable therapeutic proteins in eggs4 as a ‘bioreactor’ for industrial biotechnology.
Researchers produce transgenic chickens that express a green fluorescent protein that is expressed ubiquitously in cells of chicken embryos. These embryos are used in transplantation experiments to follow the development of different structures in the chick embryo5. The development of the chick embryo has many features in common with human development.
Roslin researchers, in collaboration with colleagues at Cambridge University, are able to suppress the transmission of avian influenza by expressing an inhibitor of viral replication in transgenic chickens6, which demonstrated the potential of using genome engineering to confer resistance to major diseases of chickens.
The first transgenic chickens that express fluorescent proteins in specific immune cells, cells of the mononuclear phagocyte lineage, to visualise the immune system at work7 are produced and characterised. Significant differences between the immune cells of the chicken and of mammals are identified.
Roslin researchers build upon methods to culture and modify chicken primordial germ cells8 (PGCs), which can then be transferred to a host embryo and develop into sperm/eggs, allowing breeding of gene-edited chickens. Production of inducibly-sterile chickens into which these cells can be implanted during embryo development results in chickens that, when they are breeding age, produce chicks derived solely from the transferred genetic material (PGCs)9. These two innovations not only provide the opportunity to archive chicken genetic resources10 but greatly accelerate genome editing to introduce beneficial variation and study fundamental processes in avian biology.
Genetically altered sterile surrogate hosts are used to regenerate rare heritage breeds of chicken from their cryopreserved PGCs11. Researchers at Roslin are harnessing the power of CRISPR technology to unravel the function of chicken genes12,13, with the award of BBSRC strategic funding for 2017- 2022. This research will provide insights in developmental biology, immunology and host-pathogen interactions, which in turn will inform vaccine development for poultry specific and zoonotic diseases and elucidate mechanisms that underpin hereditary disease in humans14,15.
- Perry, M. M. A complete culture system for the chick embryo. Nature 331, 70–72 (1988).
- Love, J., Gribbin, C., Mather, C. & Sang, H. Transgenic birds by DNA microinjection. Bio/Technology 12, 60–63 (1994).
- McGrew, M. J. et al. Efficient production of germline transgenic chickens using lentiviral vectors. EMBO Rep. 5, 728–733 (2004).
- Lillico, S. G. et al. Oviduct-specific expression of two therapeutic proteins in transgenic hens. Proc. Natl. Acad. Sci. U. S. A. 104, 1771–1776 (2007).
- Lyall, J. et al. Suppression of avian influenza transmission in genetically modified chickens. Science (80-. ). 331, 223–226 (2011).
- Davey, M. G. & Tickle, C. The chicken as a model for embryonic development. Cytogenet. Genome Res. 117, 231–239 (2007).
- Balic, A. et al. Visualisation of chicken macrophages using transgenic reporter genes: Insights into the development of the avian macrophage lineage. Development 141, 3255–3265 (2014).
- Whyte, J. et al. FGF, Insulin, and SMAD Signaling Cooperate for Avian Primordial Germ Cell Self-Renewal. Stem Cell Reports 5, 1171–1182 (2015).
- Taylor, L. et al. Efficient TALEN-mediated gene targeting of chicken primordial germ cells. Development 144, 928–934 (2017).
- Nandi, S. et al. Cryopreservation of specialized chicken lines using cultured primordial germ cells. Poult. Sci. 95, 1905–1911 (2016).
- Woodcock, M. E. et al. Reviving rare chicken breeds using genetically engineered sterility in surrogate host birds. Proc. Natl. Acad. Sci. U. S. A. 116, 20930–20937 (2019).
- Idoko-Akoh, A., Taylor, L., Sang, H. M. & McGrew, M. J. High fidelity CRISPR/Cas9 increases precise monoallelic and biallelic editing events in primordial germ cells. Sci. Rep. 8, 1–14 (2018).
- Woodcock, M. E., Idoko-Akoh, A. & McGrew, M. J. Gene editing in birds takes flight. Mamm. Genome 28, 315–323 (2017).
- Hardy, H. et al. Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion. Elife 8, (2019).
- Davey, M. G., Balic, A., Rainger, J., Sang, H. M. & McGrew, M. J. Illuminating the chicken model through genetic modification. Int. J. Dev. Biol. 62, 257–264 (2018).
Graphics: Lindsay Henderson and Alec McEachran at Science Doodles