A5076800780- Genomics and Chromatin Dynamics
- Fungal and yeast genetics research
- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- DNA Repair Mechanisms
- Chromosomal and Genetic Variations
- Animal Virus Infections Studies
- RNA Research and Splicing
- Advanced Fluorescence Microscopy Techniques
- COVID-19 epidemiological studies
- Yeasts and Rust Fungi Studies
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Epigenetics and DNA Methylation
- COVID-19 and healthcare impacts
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Microtubule and mitosis dynamics
- Fermentation and Sensory Analysis
- Sperm and Testicular Function
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Advanced Biosensing Techniques and Applications
- COVID-19 Pandemic Impacts
- Monoclonal and Polyclonal Antibodies Research
Wellcome/MRC Cambridge Stem Cell Institute
2012-2024
University of Cambridge
2011-2023
Stem Cell Institute
2020-2023
Medical Research Council
2007-2017
Western General Hospital
2003-2008
MRC Human Genetics Unit
2005-2007
Institute of Genetics and Cancer
2005
Wellcome Centre for Cell Biology
2002-2003
University of Edinburgh
1996-2003
South Thames College
1989
Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 HCWs were screened for large UK teaching hospital. Symptomatic staff household contacts additionally tested. Real-time RT-PCR was used to detect viral RNA from throat+nose self-swab. 3% group tested positive SARS-CoV-2. 17/30 (57%) truly...
SummaryTranscriptional heterogeneity within embryonic stem cell (ESC) populations has been suggested as a mechanism by which seemingly homogeneous population can initiate differentiation into an array of different types. Chromatin remodeling proteins have shown to control transcriptional variability in yeast and be important for mammalian ESC lineage commitment. Here we show that the Nucleosome Remodeling Deacetylation (NuRD) complex, is required commitment, modulates both dynamic range set...
Gametogenesis is a complex process subject to strict controls at both levels of transcription and translation. Members family conserved RNA-binding proteins encoded by the DAZ genes are required for translational regulation gene expression essential this process. Although loss associated with infertility in several organisms including humans, identity transcripts regulated vivo unknown. Using combination immunoprecipitation microarray analysis, we have identified number mRNAs that bound...
Chromatin remodeling complexes play essential roles in metazoan development through widespread control of gene expression, but the precise molecular mechanisms by which they do this vivo remain ill defined. Using an inducible system with fine temporal resolution, we show that nucleosome and deacetylation (NuRD) complex controls chromatin architecture protein binding repertoire at regulatory regions during cell state transitions. This is primarily exerted its activity while H3K27 follows...
DAZ -related genes are essential for gametogenesis in diverse metazoa: human males, a loss of is associated with infertility. These genes, expressed only germ cells, regulate the translation yet undefined set specific transcripts, and function results numerous defects throughout mitotic meiotic process cell development. In mouse model, absence autosomal Dazl gene final block at zygotene prophase. Sycp3 also meiosis, specifically formation synaptonemal complex lateral element knockout model...
Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also (Rivett et al., 2020). Here, show the proportion both and symptomatic testing rapidly declined to near-zero between 25th 24th May 2020, corresponding decline patient admissions COVID-19 during ongoing UK 'lockdown'. These data demonstrate...
Multiprotein chromatin remodelling complexes show remarkable conservation of function amongst metazoans, even though components present in invertebrates are often found as multiple paralogous proteins vertebrate complexes. In some cases, these paralogues specify distinct biochemical and/or functional activities cells. Here, we set out to define the and diversity encoded by one such group within mammalian Nucleosome Remodelling Deacetylation (NuRD) complex: Mta1, Mta2 Mta3. We find that,...
Enhancers bind transcription factors, chromatin regulators, and non-coding transcripts to modulate the expression of target genes. Here, we report 3D genome structures single mouse ES cells as they are induced exit pluripotency transition through a formative stage prior undergoing neuroectodermal differentiation. We find that there is remarkable reorganization structure where inter-chromosomal intermingling increases dramatically in state. This associated with formation large number multiway...
As genetic information is transmitted through successive generations, it passes between pluripotent cells in the early embryo and germ developing foetus adult animal. Tex19.1 encodes a protein of unknown function, whose expression restricted to cells. During male spermatogenesis, highest mitotic spermatogonia diminishes as these differentiate progress meiosis. In stem cells, also downregulated upon differentiation. However, not clear whether has an essential function or what that might be....
Abstract To understand how the nucleosome remodeling and deacetylase (NuRD) complex regulates enhancers enhancer–promoter interactions, we have developed an approach to segment extract key biophysical parameters from live-cell three-dimensional single-molecule trajectories. Unexpectedly, this has revealed that NuRD binds chromatin for minutes, decompacts structure increases enhancer dynamics. We also uncovered a rare fast-diffusing state of found restricts time spent in state. Hi-C...
Polo kinases play multiple roles in cell cycle regulation eukaryotic cells. In addition to the kinase domain, conservation at primary sequence level is also found non-catalytic region mainly three blocks, namely polo boxes. Although several studies have implicated boxes protein localisation, no systematic study elucidate of individual has been carried out. Here we show, by using fission yeast, that form a single functional unit essential for both cellular function and cell-cycle-regulated...
Abstract Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness travellers being required to quarantine for 14-days on return England in Summer 2020. identified 4,207 travel-related cases and their contacts, 827 associated genomes. Overall, was with lower rate impact greatest 16–20 age-group. 186 genomes were sufficiently unique identify clusters. Fewer genomically-linked observed index who returned countries requirement compared no...
The fission yeast plo1+ gene encodes a polo-like kinase, member of conserved family kinases which play multiple roles during the cell cycle. We show that Plo1 kinase physically interacts with anaphase-promoting complex (APC)/cyclosome through noncatalytic domain and tetratricopeptide repeat subunit, Cut23. A new cut23 mutation, specifically disrupts interaction Plo1, results in metaphase arrest. This arrest can be rescued by high expression kinase. suggest this physical is crucial for...
Replication factor C (RF-C) is a five subunit DNA polymerase (Pol) δ/ε accessory required at the replication fork for loading essential processivity PCNA onto 3′-ends of nascent strands. Here we describe genetic analysis rfc2+ gene fission yeast Schizosaccharomyces pombe encoding structural homologue budding Rfc2p and human hRFC37 proteins. Deletion from chromosome lethal but does not result in checkpoint-dependent cell cycle arrest seen cells deleted or those genes subunits either Pol δ ε....
Abstract Enhancer-promoter dynamics are crucial for the spatiotemporal control of gene expression, but it remains unclear whether these controlled by chromatin regulators, such as nucleosome remodelling and deacetylase (NuRD) complex. The NuRD complex binds to all active enhancers modulate transcription here we use Hi-C experiments show that blurs TAD boundaries increases proximity intermediate-range (~1 Mb) genomic sequences enhancer-promoter interactions. To understand alters 3D genome...
Differentiation of mammalian pluripotent cells involves large-scale changes in transcription and, among the molecules that orchestrate these changes, chromatin remodellers are essential to initiate, establish and maintain a new gene regulatory network. The Nucleosome Remodelling Deacetylation (NuRD) complex is highly conserved remodeller which fine-tunes expression embryonic stem cells. While function NuRD mouse has been well defined, no study yet defined human Here we find while activity...
An analysis of simple carbohydrates was undertaken using attenuated total reflection (ATR) and Fourier transform infrared (FTIR) spectroscopy. Spectra were obtained glucose in aqueous solution the results qualitatively quantitatively assessed for three new ATR accessories. The same method then used to study presence sucrose solution. A has also been made whole plant cells including yeasts Pelargonium sp. Triticum spectra have determine cellular components monitor enzymatic digestion cell...