Exploiting stem cell and gene editing technologies towards discovery of genetic variants important for muscle development and meat production

点击翻译按钮获取中文摘要

Increasing meat production and quality is a top global priority to sustainably meet the protein requirements of a growing human population. Efficiently increasing production through genetic selection of livestock requires knowledge of key genes and gene variants involved in muscle development. Thousands of genetic variants associated with meat production and quality have already been found in previous studies. Identifying those specific variants that naturally and effectively promote formation of muscle over fat during development will be extremely useful as such knowledge could be applied to dramatically increase meat production in a sustainable manner. Critically, to achieve this, robust cell systems will be needed to functionally test relevant variants in vitro before they can be used in animal selection programmes (1). The advent of novel stem cell technologies such as induced pluripotent stem cells (iPSCs) together with next-generation gene-editing approaches such as CRISPR/Cas9 provides a unique opportunity to achieve that important goal. With this in mind, this project will aim to use cutting-edge stem cell and gene editing technologies to generate for the first time a cell-based platform that can be used to robustly identify genes and genetic variants responsible for optimum muscle development in livestock, namely pigs and cattle. This will be achieved through two well-defined objectives: 1. Using our unique expertise in large animal stem cells (2, 3), the student will use both native tissue stem cells (mesenchymal stem cells) and iPSCs to generate, for the first time, muscle and adipose cell lines from species of interest (pig, cow).2. Methods will be optimised to edit the genome of these cells using CRISPR-Cas9 technology with the purpose of testing natural genetic variants associated with optimum muscle and adipose tissue development. As proof-of-concept, genes already known to be involved in muscle and adipose development will be initially targeted.3. Genetic variants known to be associated with optimum meat production in each species will be targeted to test their effect on muscle and adipose development, with a view to eventually incorporate the information obtained into relevant animal breeding programmes. The project will benefit from the supervisor's expertise in stem cell biology (Dr. Donadeu) and livestock genetics (Prof. Hickey), as well as unique expertise and facilities for iPSC generation from our industrial partner. The student will acquire a solid understanding of stem cell biology, muscle and adipose tissue biology, cutting-edge gene editing technologies, as well as become acquainted with farm animal genetics. He/she will become proficient in stem cell culture, differentiation and genetic manipulation, and gene and protein analyses (PCR, immunochemistry, western blotting). In addition, through his/her placement with the industrial partner, the student will acquire a solid understanding of industry including project management, business strategy and finance.