A5086655876- Animal Genetics and Reproduction
- CRISPR and Genetic Engineering
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Chromosomal and Genetic Variations
- Pluripotent Stem Cells Research
- RNA Interference and Gene Delivery
- Silk-based biomaterials and applications
- Rangeland and Wildlife Management
- Mental Health Research Topics
- Behavioral Health and Interventions
- Microtubule and mitosis dynamics
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Botany and Plant Ecology Studies
- Muscle Physiology and Disorders
- Biosimilars and Bioanalytical Methods
- School Health and Nursing Education
- RNA Research and Splicing
- Genetic diversity and population structure
- Botany, Ecology, and Taxonomy Studies
- Drug Transport and Resistance Mechanisms
- Viral gastroenteritis research and epidemiology
- Diet and metabolism studies
- Livestock and Poultry Management
Roslin Institute
2016-2025
University of Edinburgh
2016-2025
Derbyshire County Council
2024
Marine and Freshwater Research Institute
2003
The University of Texas MD Anderson Cancer Center
1995
Baylor College of Medicine
1995
Mice homozygous for the targeted deletion of c/ebp α gene, which expresses CCAAT/enhancer-binding protein (C/EBPα), did not store hepatic glycogen and died from hypoglycemia within 8 hours after birth. In these mutant mice, amounts synthase messenger RNA were 50 to 70 percent normal transcriptional induction genes two gluconeogenic enzymes, phosphoenolpyruvate carboxykinase glucose-6-phosphatase, was delayed. The hepatocytes adipocytes mice failed accumulate lipid expression gene uncoupling...
The derivation of germ-line competent avian primordial germ cells establishes a cell-based model system for the investigation cell differentiation and production genetically modified animals. Current methods to modify using DNA or retroviral vectors are inefficient prone epigenetic silencing. Here, we validate use transposable elements genetic manipulation cells. We demonstrate that chicken can be in vitro elements. Both piggyBac Tol2 transposons efficiently transpose transposon integration...
Precise self-renewal of the germ cell lineage is fundamental to fertility and reproductive success. The early precursors for lineage, primordial cells (PGCs), survive proliferate in several embryonic locations during their migration gonad. By elucidating active signaling pathways migratory PGCs vivo, we were able create culture conditions that recapitulate this environment. In defined medium without feeder cells, growth factors FGF2, insulin, Activin A, through cognate-signaling pathways,...
Background Avian primordial germ cells (PGCs) have significant potential to be used as a cell-based system for the study and preservation of avian germplasm, genetic modification genome. It was previously reported that PGCs from chicken embryos can propagated in culture contribute cell lineage host birds. Principal Findings We confirm these results by demonstrating different layer breed chickens extended periods vitro. demonstrate intracellular signalling through PI3K MEK is necessary PGC...
In this work we use TALE nucleases (TALENs) to target a reporter construct the DDX4 (vasa) locus in chicken primordial germ cells (PGCs). Vasa is key cell determinant many animal species and posited control avian formation. We show that TALENs mediate homology-directed repair of on Z sex chromosome at high (8.1%) efficiencies. Large genetic deletions 30 kb encompassing entire were also created using single TALEN pair. The targeted PGCs germline competent used produce null offspring. knockout...
Poultry is the most abundant livestock species with over 60 billion chickens raised globally per year. The majority of chicken are produced from commercial flocks, however many indigenous breeds play an important role in rural economies as they well adapted to local environmental and scavenging conditions. ability make precise genetic changes will permit validation variants responsible for climate adaptation disease resilience, transfer beneficial alleles between breeds. Here, we generate a...
Abstract Chickens genetically resistant to avian influenza could prevent future outbreaks. In chickens, A virus (IAV) relies on host protein ANP32A. Here we use CRISPR/Cas9 generate homozygous gene edited (GE) chickens containing two ANP32A amino acid substitutions that viral polymerase interaction. After IAV challenge, 9/10 remain uninfected. Challenge with a higher dose, however, led breakthrough infections. Breakthrough contained mutations conferred adaptation the chicken Unexpectedly,...
The human C/EBP alpha gene promoter shares significant sequence homology with that of the mouse but has a different mechanism autoregulation. Activation murine by direct binding to site within 200 bp transcriptional start was shown elevate activity approximately threefold (R. J. Christy, K. H. Kaestner, D. E. Geiman, and M. Lane, Proc. Natl. Acad. Sci. USA 88:2593-2597, 1991; Legraverend, P. Antonson, Flodby, G. Xanthapoulos, Nucleic Acids Res. 21:1735-1742, 1993). Unlike its counterpart,...
Significance In the fields of conservation biology and sustainable agriculture, ability to cryopreserve revive animal species is paramount efforts preserve genetic diversity. An innovative approach use sterile surrogate host animals for transplantation reproductive germ cells from rare/endangered animals. This technology has previously been utilized in mammals but particular importance with lipid-filled zygotes/embryos, such as fish birds, which render cryopreservation techniques...
Birds have a sex chromosome system in which females are heterogametic (ZW) and males homogametic (ZZ). The differentiation of avian chromosomes from ancestral autosomes entailed the loss most genes W during evolution. However, to what extent mechanisms evolved that counterbalance consequences this extensive gene dosage reduction female birds has remained unclear. Here we report functional vivo evolutionary analyses Z-chromosome-linked microRNA (miR-2954) with strongly male-biased expression...
Biosecurity and sustainability in poultry production requires reliable germplasm conservation. Germplasm conservation is more challenging comparison to other livestock species. Embryo cryopreservation not feasible for egg-laying animals, chicken semen has variable success different breeds. A potential solution the of committed diploid stem cell precursors gametes, primordial germ cells (PGCs). Primordial are lineage-restricted found at early embryonic stages birds form sperm eggs. We...
Abstract Primordial germ cells (PGCs), the embryonic precursors of sperm and egg, are used for introduction genetic modifications into avian genome. Introduction small defined sequences using genome editing has not been demonstrated in bird species. Here, we compared oligonucleotide-mediated HDR wild type SpCas9 (SpCas9-WT) high fidelity SpCas9-HF1 PGCs show that many loci chicken can be precise edited donors containing CRISPR/Cas9-blocking mutations positioned protospacer adjacent motif...
Effective mucosal immunity in the intestine involves a fine balance between tolerance of microbiome, recognition and elimination pathogens, inflammatory tissue injury. The anti-inflammatory cytokine IL10 regulates these processes intestines mice humans; activity is also conserved birds. To determine function avian immunity, we generated germ line modifications chicken locus to abolish or reduce expression. In vitro analysis macrophage response lipopolysaccharide confirmed loss protein...
The zinc finger transcription factor PRDM14, part of the PR domain containing protein family, is critical for mammalian primordial germ cell (PGC) specification, epigenetic reprogramming and maintaining naïve pluripotency in stem cells. However, PRDM14's role other species not well understood. In chicken, PRDM14 broadly expressed early embryo, before becoming restricted to forming neural plate, migratory PGCs later adult testes. To investigate we generated two independent targeted chicken...
Abstract Mitotically active embryonic reproductive cells, the primordial germ cells (PGCs), are an ideal cell type for cryopreserving functional avian species. Their low number in embryo, however, renders cryopreservation and germline transmission methodologies difficult. Here, we develop a culture medium long-term vitro of PGCs from goose, Anser anser domesticus . In contrast to chicken, goose PGC self-renewal is dependent on TGF-β family member, BMP4, and, conversely, inhibited by Activin...
Chickens are an important resource for smallholder farmers who raise locally adapted, genetically distinct breeds eggs and meat. The development of efficient reproductive technologies to conserve regenerate chicken safeguards existing biodiversity secures poultry genetic resources climate resilience, biosecurity, future food production. majority the over 1600 raised in low lower middle income countries under resource-limited, small-scale production systems, which necessitates a low-tech,...
In this work, we describe a single piggyBac transposon system containing both tet-activator and doxycycline-inducible expression cassette. We demonstrate that gene product can be conditionally expressed from the integrated second simultaneously targeted by short hairpin RNA contained within transposon, in vivo mammalian avian cell lines. applied to stably modify chicken primordial germ (PGC) lines vitro induce reporter at specific developmental stages after injection of transposon-modified...
In birds, males are the homogametic sex (ZZ) and females heterogametic (ZW). Here, we investigate role of chromosomal germ cell competition on avian differentiation. We recently developed genetically sterile layer cockerels hens for use as surrogate hosts primordial (PGC) transplantation. Using in vitro propagated cryopreserved PGCs from a pedigree Silkie broiler breed, now demonstrate that injected with same have normal fertility produced pure breed offspring when directly mated to each...
Abstract Background Regulatory elements that control expression of specific genes during development have been shown in many cases to contain functionally-conserved modules can be transferred between species and direct gene a comparable developmental pattern. An example such module has identified at the rat myosin light chain ( MLC ) 1/3 locus, which well characterised transgenic mouse studies. This locus contains two promoters encoding alternatively spliced isoforms alkali chain. These are...
Primordial germ cells (PGCs) are germline-restricted embryonic that form the functional gametes of adult animal. The use avian PGCs in biobanking and producing genetically modified birds has driven research on vitro propagation manipulation these cells. In species, hypothesized to be sexually undetermined at an early stage undergo differentiation into oocyte or spermatogonial fate dictated by extrinsic factors present gonad. However, chicken male female require different culture conditions,...
This research investigates role demands and musculoskeletal pain (MSP) in UK Early Childhood Education (ECE) workforce (N = 196). Associations between frequency of actions construing higher risk to health, MSP, need take sickness absence considering changing jobs are considered. Differences practitioners leaders investigated. Evaluation severity, frequency, gathered, for the first time ECE staff, duration, onset bothersomeness. 98 % participants reported associated with carrying out...
Rodent × human hybrids containing single chromosomes are valuable tools in the study of genetics. Using a retrovirus carrying neomycin gene, we generated neomycin-resistant (neo<sup>r</sup>) pool diploid fibroblasts. Following fusion microcells prepared from this to mouse A9 cells, obtained four neo<sup>r</sup> chromosome 2, 3, 5, or 15.
The purpose of our research was to design, implement and evaluate a cognitive-behavioral asthma self-management program for adults. Seventeen adults with completed an eight-week course (two hours, once week) that consisted interactive small group discussions behavior change procedure. were led by multi-disciplinary faculty (nurse, respiratory therapist, allergist, social worker, psychologist). Following each weekly discussion, participants would attempt related the discussion. At following...