ORCID Profile
0000-0002-2918-1605
Current Organisation
The University of Edinburgh
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Publisher: Elsevier BV
Date: 2014
DOI: 10.1038/MTM.2014.10
Publisher: The American Association of Immunologists
Date: 15-09-2016
Abstract: Expression of Csf1r in adults is restricted to cells of the macrophage lineage. Transgenic reporters based upon the Csf1r locus require inclusion of the highly conserved Fms-intronic regulatory element for expression. We have created Csf1r-EGFP transgenic sheep via lentiviral transgenesis of a construct containing elements of the mouse Fms-intronic regulatory element and Csf1r promoter. Committed bone marrow macrophage precursors and blood monocytes express EGFP in these animals. Sheep monocytes were ided into three populations, similar to classical, intermediate, and nonclassical monocytes in humans, based upon CD14 and CD16 expression. All expressed EGFP, with increased levels in the nonclassical subset. Because Csf1r expression coincides with the earliest commitment to the macrophage lineage, Csf1r-EGFP bone marrow provides a tool for studying the earliest events in myelopoiesis using the sheep as a model.
Publisher: Wiley
Date: 24-02-2016
DOI: 10.1002/CBF.3173
Publisher: Cambridge University Press (CUP)
Date: 14-01-2011
DOI: 10.1017/S0021859610001188
Abstract: The challenge for the next 50 years is to increase the productivity of major livestock species to address the food needs of the world, while at the same time minimizing the environmental impact. The present review presents an optimistic view of this challenge. The completion of genome sequences, and high-density analytical tools to map genetic markers, allows for whole-genome selection programmes based on linkage disequilibrium for a wide spectrum of traits, simultaneously. In turn, it will be possible to redefine genetic prediction based on allele sharing, rather than pedigree relationships and to make breeding value predictions early in the life of the peak sire. Selection will be applied to a much wider range of traits, including those that are directed towards environmental or adaptive outcomes. In parallel, reproductive technologies will continue to advance to allow acceleration of genetic selection, probably including recombination in vitro. Transgenesis and/or mutagenesis will be applied to introduce new genetic variation or desired phenotypes. Traditional livestock systems will continue to evolve towards more intensive integrated farming modes that control inputs and outputs to minimize the impact and improve efficiency. The challenges of the next 50 years can certainly be met, but only if governments reverse the long-term disinvestment in agricultural research.
Publisher: Public Library of Science (PLoS)
Date: 15-09-2017
Publisher: Springer Science and Business Media LLC
Date: 02-07-2015
Publisher: Cold Spring Harbor Laboratory
Date: 27-08-2020
DOI: 10.1101/2020.08.27.266155
Abstract: Invasive species are among the major driving forces behind bio ersity loss. Gene drive technology may offer a humane, efficient and cost-effective method of control. For safe and effective deployment it is vital that a gene drive is both self-limiting and can overcome evolutionary resistance. We present HD-ClvR, a novel combination of CRISPR-based gene drives that eliminates resistance and localises spread. As a case study, we model HD-ClvR in the grey squirrel ( Sciurus carolinensis ), which is an invasive pest in the UK and responsible for both bio ersity and economic losses. HD-ClvR combats resistance allele formation by combining a homing gene drive with a cleave-and-rescue gene drive. The inclusion of a self-limiting daisyfield gene drive allows for controllable localisation based on animal supplementation. We use both randomly mating and spatial models to simulate this strategy. Our findings show that HD-ClvR can effectively control a targeted grey squirrel population, with little risk to other populations. HD-ClvR offers an efficient, self-limiting and controllable gene drive for managing invasive pests.
Publisher: MDPI AG
Date: 13-02-2023
DOI: 10.3390/APPLBIOSCI2010006
Abstract: Scientists have long sought a technology to humanely control populations of damaging invasive pests in a species-specific manner. Gene drive technology could see this become a reality. This review charts the twists and turns on the road to developing gene drives in vertebrates. We focus on rodents, as these will likely be the first targets, and trace the journey from the early understanding of selfish genetic elements to engineering gene drives in mice before discussing future research focuses and the crucial role that public perception and governance will play in the application of this technology. The realisation of robust gene drive strategies in vertebrate pests has the potential to revolutionise biocontrol.
Publisher: Oxford University Press (OUP)
Date: 07-2010
Publisher: Springer Science and Business Media LLC
Date: 24-01-2018
DOI: 10.1038/S41467-017-02729-0
Abstract: Mutations in C9ORF72 are the most common cause of familial amyotrophic lateral sclerosis (ALS). Here, through a combination of RNA-Seq and electrophysiological studies on induced pluripotent stem cell (iPSC)-derived motor neurons (MNs), we show that increased expression of GluA1 AMPA receptor (AMPAR) subunit occurs in MNs with C9ORF72 mutations that leads to increased Ca 2+ -permeable AMPAR expression and results in enhanced selective MN vulnerability to excitotoxicity. These deficits are not found in iPSC-derived cortical neurons and are abolished by CRISPR/Cas9-mediated correction of the C9ORF72 repeat expansion in MNs. We also demonstrate that MN-specific dysregulation of AMPAR expression is also present in C9ORF72 patient post-mortem material. We therefore present multiple lines of evidence for the specific upregulation of GluA1 subunits in human mutant C9ORF72 MNs that could lead to a potential pathogenic excitotoxic mechanism in ALS.
Publisher: Cold Spring Harbor Laboratory
Date: 05-2017
DOI: 10.1101/132696
Abstract: Sheep are a key source of meat, milk and fibre for the global livestock sector, and an important biomedical model. Global analysis of gene expression across multiple tissues has aided genome annotation and supported functional annotation of mammalian genes. We present a large-scale RNA-Seq dataset representing all the major organ systems from adult sheep and from several juvenile, neonatal and prenatal developmental time points. The Ovis aries reference genome (Oar v3.1) includes 27,504 genes (20,921 protein coding), of which 25,350 (19,921 protein coding) had detectable expression in at least one tissue in the sheep gene expression atlas dataset. Network-based cluster analysis of this dataset grouped genes according to their expression pattern. The principle of ‘guilt by association’ was used to infer the function of uncharacterised genes from their co-expression with genes of known function. We describe the overall transcriptional signatures present in the sheep gene expression atlas and assign those signatures, where possible, to specific cell populations or pathways. The findings are related to innate immunity by focusing on clusters with an immune signature, and to the advantages of cross-breeding by examining the patterns of genes exhibiting the greatest expression differences between purebred and crossbred animals. This high-resolution gene expression atlas for sheep is, to our knowledge, the largest transcriptomic dataset from any livestock species to date. It provides a resource to improve the annotation of the current reference genome for sheep, presenting a model transcriptome for ruminants and insight into gene, cell and tissue function at multiple developmental stages. Sheep are ruminant mammals kept as livestock for the production of meat, milk and wool in agricultural industries across the globe. Genetic and genomic information can be used to improve production traits such as disease resiliance. The sheep genome is however missing important information relating to gene function and many genes, which may be important for productivity, have no informative gene name. This can be remedied using RNA-Sequencing to generate a global expression profile of all protein-coding genes, across multiple organ systems and developmental stages. Clustering genes based on their expression profile across tissues and cells allows us to assign function to those genes. If for ex le a gene with no informative gene name is expressed in macrophages and is found within a cluster of known macrophage related genes it is likely to be involved in macrophage function and play a role in innate immunity. This information improves the quality of the reference genome and provides insight into biological processes underlying the complex traits that influence the productivity of sheep and other livestock species.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.TIBTECH.2017.10.001
Abstract: Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene drives (GDs) could be used to spread desirable genetic elements through wild populations. With the imminent development of this technology in vertebrates, we believe that it is timely to highlight two forms of sex-ratio distorting GDs that show potential as pest management tools.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Bruce Whitelaw.