A5082233070- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Genetics and Neurodevelopmental Disorders
- SARS-CoV-2 and COVID-19 Research
- SARS-CoV-2 detection and testing
- Gene expression and cancer classification
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Plant Molecular Biology Research
- Cancer-related gene regulation
- Microtubule and mitosis dynamics
- Monoclonal and Polyclonal Antibodies Research
- Genetic Mapping and Diversity in Plants and Animals
- Protein Degradation and Inhibitors
- interferon and immune responses
- Genomic variations and chromosomal abnormalities
- Cancer therapeutics and mechanisms
- vaccines and immunoinformatics approaches
Western General Hospital
2012-2025
Institute of Genetics and Cancer
2015-2024
University of Edinburgh
2015-2024
Medical Research Council
2005-2024
Edinburgh College
2020
MRC Human Genetics Unit
2003-2018
Institute of Molecular Genetics
2013
Edinburgh Cancer Research
2007-2013
St. Luke's Episcopal Hospital
2009
Human Factors (Norway)
2005
Highlights•Depletion or kinase inhibition of FAK can cause squamous cell carcinoma regression•FAK promotes tumor evasion by inducing an immuno-suppressive microenvironment•Nuclear transcription chemokines that drive recruitment Tregs•FAK-induced Tregs inhibit cytotoxic CD8+ T cells, allowing tolerance and growthSummaryFocal adhesion (FAK) anti-tumor immune evasion. Specifically, the activity nuclear-targeted in (SCC) cells drives exhaustion regulatory (Tregs) microenvironment regulating...
Chemical inhibitors of histone deacetylase (HDAC) activity are used as experimental tools to induce hyperacetylation and deregulate gene transcription, but it is not known whether the inhibition HDACs plays any part in normal physiological regulation transcription. Using both vitro vivo assays, we show that lactate, which accumulates when glycolysis exceeds cell's aerobic metabolic capacity, an endogenous HDAC inhibitor, deregulating transcription HDAC-dependent manner. Lactate a relatively...
Higher eukaryotic chromosomes are organized into topologically constrained functional domains; however, the molecular mechanisms required to sustain these complex interphase chromatin structures unknown. A stable matrix underpinning nuclear organization was hypothesized, but idea abandoned as more dynamic models of behavior became prevalent. Here, we report that scaffold attachment factor (SAF-A), originally identified a structural protein, interacts with chromatin-associated RNAs (caRNAs)...
Highlights•HiP-HoP: highly predictive heteromorphic polymer model to analyze chromatin structure•Polymer simulations use widely available epigenetic and protein binding data as input•Validate HiP-HoP at complex loci using 3D FISH Capture-C•Simulations uncover striking conformational variability in fiber foldingSummaryChromatin folded into macromolecular structures is often analyzed by chromosome conformation capture (3C) fluorescence situ hybridization (FISH) techniques, but these frequently...
Centromeres are scaffolds for the assembly of kinetochores that ensure chromosome segregation during cell division. How vertebrate centromeres obtain a three-dimensional structure to accomplish their primary function is unclear. Using super-resolution imaging, capture-C, and polymer modeling, we show partitioned by condensins into two subdomains mitosis. The bipartite found in human, mouse, chicken cells therefore fundamental feature centromeres. Super-resolution imaging electron tomography...
It has been reported that DNA methyltransferase 1-deficient (Dnmt1-/-) embryonic stem (ES) cells are hypomethylated (20% CpG methylation) and die through apoptosis when induced to differentiate. Here, we show Dnmt[3a-/-,3b-/-] ES with just 0.6% of their dinucleotides behave differently: the majority within culture partially or completely blocked in ability initiate differentiation, remaining viable while retaining cell characteristics alkaline phosphatase Oct4 expression. Restoration...
Centromeres are essential for chromosome segregation and specified epigenetically by the presence of histone H3 variant CENP-A. In flies humans, replenishment centromeric mark is uncoupled from DNA replication requires removal “placeholder” nucleosomes. Although transcription at centromeres has been previously linked to loading new CENP-A, underlying molecular mechanism remains poorly understood. Here, we used Drosophila melanogaster tissue culture cells show that actively transcribing RNA...
DNA methylation has been implicated in chromatin condensation and nuclear organization, especially at sites of constitutive heterochromatin. How this is mediated not clear. In study, using mutant mouse embryonic stem cells completely lacking methylation, we show that affects organization nucleosome structure but compaction. the absence there increased clustering pericentric heterochromatin extensive changes primary structure. Global levels histone H3 acetylation are altered, a decrease...
Abstract In living cells, the 3D structure of gene loci is dynamic, but this not revealed by 3C and FISH experiments in fixed samples, leaving a notable gap our understanding. To overcome these limitations, we applied highly predictive heteromorphic polymer (HiP-HoP) model to determine chromatin fiber mobility at Pax6 locus three mouse cell lines with different transcription states. While transcriptional activity minimally affects movement 40-kbp regions, observed that motion smaller 1-kbp...