Dr Lydia Teboul has been awarded the 2020 International Society for Transgenic Technologies (ISTT) 3Rs Prize. This prize recognises Lydia’s work in developing a technique that implements the reduction principle of the 3Rs, to reduce the number of animals used in research.
Gene editing has vastly improved in recent years, accelerating genetic research. Specifically, CRISPR-Cas9 technology, which has revolutionised genome editing, provides the possibility to directly target and modify regions of the genome to create precise mutations. However, whilst the new tools are specific and efficient when delivered into an embryo, not every cell in the modified animal will carry the desired nor the same mutation. This results in genetically complex animals called mosaics. It is essential that animals with the correct mutation are identified and selected for further breeding to establish mouse colonies for biological studies. However, classical genotyping methods are not well adapted to unequivocally characterise these mosaic animals.
Alongside the development of new technologies for genome engineering, more protocols to efficiently identify and remove the animals that bear the wrong mutations are required. Lydia and her group have developed a method that quickly and accurately screens the modified animal for allele variations to identify and validate desired animals before breeding. They have developed a long-read based sequencing method that sequences the genome to identify if the correct mutation is present or not. This technique creates a better selection process, ensuring only animals with the correct mutation are bred and used further in research, overall preventing the unnecessary breeding of animals.
Lydia is the Head of Molecular and Cellular Biology at the Mary Lyon Centre and manages a number of services including, genome engineering, expression analysis and embryo phenotyping. Lydia runs the CRISPR and Conditional Transgenic courses at our Advance Training centre and also leads the Genome Editing Mice for Medicine programme. With a focus on genome engineering and research reproducibility, Lydia’s team introduces current and new protocols into the molecular services and training courses that MRC Harwell offers to the research community.
“Genome editing creates unusual animal that are difficult to characterise because of their genetic complexity. However, they represent an opportunity to reduce the number of animals we use, as each of them contains more mutations. Our new protocol, with long-read sequencing, allows us to work with these mutation-rich animals and identify those that bear the right mutation with more certainty, so false-positive animals are not bred, thus reducing the number of animals used for genome editing.”Dr. Lydia Teboul