Ongoing Research

Project: Engineering biology toolbox for precision breeding

Team: Mike McGrew (PI), Finn Grey, Mark Stevens, Joe Rainger, Jacqueline Smith, Denis Headon, James Glover, Diego Robledo, Xavier Donadeu, Tom Burdon

Precision breeding and genome engineering projects in livestock are often constrained by a lack of specialist tools, protocols, and resources. This project will establish an Engineering Biology Toolbox to help address these challenges, by developing new reagents, cell lines, and methodologies for livestock genome engineering. Initial efforts will focus on multiplex base editing to rapidly introduce favourable variants underlying complex traits, alongside scalable CRISPR-based screening approaches in avian germ cells. The toolbox will create genome engineering tools and protocols that can be applied across a wide range of livestock research. These resources will be developed with the intention of making them accessible to the wider research community, helping to reduce duplication of effort and accelerate the translation of genetic discoveries into precision breeding applications.

Project: Generating livestock cell lines with landing pads for efficient transgene expression. 

Team: Finn Grey (PI), Mike McGrew, Joe Rainger, Christine Tait Burkard, Simon Lillico, Holly Hardy, Rose Blake, Tom Burdon, Tim Bean, James Prendergast, Dirk Kleinjan (CEB, UoE), Rennos Fragkoudis (CEB, UoE), Susan Rosser (CEB, UoE). 

Introducing genes into livestock cells is often inefficient and unpredictable because DNA can integrate at random locations in the genome. This project will develop “landing pad” technologies in livestock species that enable genes to be inserted precisely into safe genomic locations, ensuring reliable expression while avoiding unwanted effects. This project will establish and validate landing pads in chicken cell lines to support ongoing research on antiviral genes and large-scale CRISPR screening, before extending the approach to pigs and cattle. By creating a versatile toolkit for targeted DNA and transgene integration across farmed animal species, the project will provide a valuable resource for genome engineering, functional genomics, and precision breeding research.

Project: New tractable models: engineering livestock stem cell potential

Team: Tom Burdon (PI), Tom Watson

Improvements in genetics are essential for enhancing Livestock productivity and health, and are critical if we are going to maximise food security and minimise negative impacts on our environment and climate. A key element in this endeavour is developing technologies that enable efficient functional analysis of genetic variants in a biologically relevant context. Pluripotent stem cells (PSCs) are a limitless source of genetically normal differentiated cells with which to perform these analyses in the laboratory.

At the Roslin Institute, we have generated a suite of PSC lines from Livestock and demonstrated they can differentiate into a variety of cell types, including blood cells, neurons, muscle etc, and are readily genetically modified to test gene function. In this project, we will use pig PSCs to address three objectives. First, we will attempt to prevent infection of macrophages by the lethal pig pathogen African Swine Fever Virus by disrupting candidate host genes that the virus uses to enter and take control of the host cell. Second, we will generate engineered reporter PSCs that allow us to better monitor the differentiation and activity of PSC-derived cells. And third, we will genetically engineer PSCs so that their differentiation is more tightly controlled and efficient. Collectively, these objectives will strengthen the immediate utility and future potential of livestock stem cells as a platform for studying and improving livestock genetics.

Project: Technologies for inducible transgenesis and chromosome engineering to achieve sex skewing in chicken

Team: Denis Headon (PI), Ian Adams, Mike McGrew, Samer Halabi

In the egg-laying industry, only female chicks are needed for egg production, resulting in billions of male chicks being culled shortly after hatching each year. This practice raises significant ethical concerns and creates economic inefficiencies. Our project aims to develop innovative genetic tools to bias chick sex ratios towards females, reducing the need for male chick culling.

In birds, females carry Z and W sex chromosomes, while males carry two Z chromosomes. Because the mother determines the sex of the offspring, we are exploring two complementary approaches. The first, “sex skewing at hatch,” uses light-activated genetic tools to selectively eliminate male embryos by targeting Z chromosome inheritance. The second, “sex skewing at lay,” aims to modify the Z chromosome so it is less likely to be passed into eggs during meiosis.

Together, these approaches could provide a practical and humane alternative to male chick culling while advancing genetic technologies for poultry research.

Project: An efficient and precise genome engineering toolbox for aquaculture

Team: Tim Bean (PI), Diego Robledo, Nick Wade, Tim Regan, Robert Stewart, Alexandra Florea

This project will establish an Aquaculture Genome Engineering Toolbox to enable large-scale functional genomics and gene discovery in farmed fish species. Although genome-wide CRISPR screens have enormous potential to identify genes influencing disease resistance, growth, and other economically important traits, the foundational resources needed to perform these studies are largely lacking in aquaculture species. Focusing on salmon and tilapia species, we will develop key enabling technologies including Cas9-expressing cell lines, optimised gene-delivery methods, and species-specific CRISPR screening libraries. Together, these resources will provide a platform for genome-scale genetic studies, accelerating research and supporting the development of healthier, more resilient aquaculture stocks.