A5066647656- RNA Research and Splicing
- Fungal and yeast genetics research
- Genomics and Chromatin Dynamics
- Gene Regulatory Network Analysis
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Bioinformatics and Genomic Networks
- Microbial Metabolic Engineering and Bioproduction
- Cancer-related molecular mechanisms research
- Single-cell and spatial transcriptomics
- Plant and Fungal Interactions Research
- Molecular Biology Techniques and Applications
- T-cell and B-cell Immunology
- Gene expression and cancer classification
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Glioma Diagnosis and Treatment
- DNA Repair Mechanisms
- Immune Cell Function and Interaction
- Genomics and Phylogenetic Studies
- Chromosomal and Genetic Variations
- Bacterial Genetics and Biotechnology
- thermodynamics and calorimetric analyses
- Cell Image Analysis Techniques
- Viral Infectious Diseases and Gene Expression in Insects
University College London
2013-2025
CRUK Lung Cancer Centre of Excellence
2023-2025
MRC London Institute of Medical Sciences
2014-2024
Imperial College London
2015-2024
NIHR Imperial Biomedical Research Centre
2021-2023
ORCID
2022
Medical Research Council
2022
Hammersmith Hospital
2020
MRC Clinical Trials Unit at UCL
2016
Cancer Institute (WIA)
2014
SummaryData on absolute molecule numbers will empower the modeling, understanding, and comparison of cellular functions biological systems. We quantified transcriptomes proteomes in fission yeast during proliferation quiescence. This rich resource provides first comprehensive reference for all RNA most protein concentrations a eukaryote under two key physiological conditions. The integrated data set supports quantitative biology affords unique insights into cell regulation. Although mRNAs...
In the life sciences, many measurement methods yield only relative abundances of different components in a sample. With such relative—or compositional—data, differential expression needs careful interpretation, and correlation—a statistical workhorse for analyzing pairwise relationships—is an inappropriate measure association. Using yeast gene data we show how correlation can be misleading present proportionality as valid alternative data. We strength between two variables meaningfully...
Schwann cell dedifferentiation from a myelinating to progenitor-like underlies the remarkable ability of peripheral nerves regenerate following injury. However, molecular identity differentiated and dedifferentiated states in vivo has been elusive. Here, we profiled cells acutely purified intact wound distal regions severed nerves. Our analysis reveals novel facets response, including acquisition mesenchymal traits Myc module. Furthermore, constitute different populations, with displaying...
SummaryGene expression is controlled at multiple layers, and cells may integrate different regulatory steps for coherent production of proper protein levels. We applied various microarray-based approaches to determine key gene-expression intermediates in exponentially growing fission yeast, providing genome-wide data translational profiles, mRNA steady-state levels, polyadenylation start-codon sequence context, half-lives, RNA polymerase II occupancy. uncovered widespread unexpected...
Interactions between major histocompatibility complex (MHC) molecules expressed on stromal cells and antigen-specific receptors T shape the repertoire of mature lymphocytes emerging from thymus. Some thymocytes with appropriate are stimulated to undergo differentiation fully state (positive selection), whereas others strongly autoreactive triggered programmed cell death before completing this process (negative selection). The quantitative impact negative selection potentially available is...
Cell size varies during the cell cycle and in response to external stimuli. This requires tight coordination, or "scaling," of mRNA protein quantities with volume order maintain biomolecule concentrations density. Evidence populations single cells indicates that scaling relies on coordination transcription rates size. Here, we use a combination single-molecule fluorescence situ hybridization (smFISH), time-lapse microscopy, mathematical modeling fission yeast uncover precise molecular...
Normalization of single-cell RNA-sequencing (scRNA-seq) data is a prerequisite to their interpretation. The marked technical variability, high amounts missing observations and batch effect typical scRNA-seq datasets make this task particularly challenging. There need for an efficient unified approach normalization, imputation correction.Here, we introduce bayNorm, novel Bayesian scaling inference counts. method's likelihood function follows binomial model mRNA capture, while priors are...
Abstract Glioblastomas are hierarchically organised tumours driven by glioma stem cells that retain partial differentiation potential. Glioma maintained in specialised microenvironments, but whether, or how, they undergo lineage progression outside of these niches remains unclear. Here we identify the white matter as a differentiative niche for glioblastomas with oligodendrocyte competency. Tumour contact acquire pre-oligodendrocyte fate, resulting decreased proliferation and invasion....
Glioblastoma (GBM) recurrence originates from invasive margin cells that escape surgical debulking, but to what extent these resemble their bulk counterparts remains unclear. Here, we generated three immunocompetent somatic GBM mouse models, driven by subtype-associated mutations, compare matched and cells. We find that, regardless of tumors converge on common sets neural-like cellular states. However, have distinct biology. Injury-like programs associated with immune infiltration dominate...
The development of DNA sequencing more than 30 years ago has profoundly impacted biological research. In the last couple years, remarkable technological innovations have emerged that allow direct and cost-effective complex samples at unprecedented scale speed. These next-generation technologies make it feasible to sequence not only static genomes, but also entire transcriptomes expressed under different conditions. other powerful applications are rapidly revolutionizing way genomic studies...
High-throughput sequencing of cDNA has been used to study eukaryotic transcription on a genome-wide scale single base pair resolution. In order compensate for the high ribonuclease activity in bacterial cells, we have devised an equivalent technique optimized studying complete prokaryotic transcriptomes that minimizes manipulation RNA sample. This new approach uses Illumina technology sequence single-stranded (ss) cDNA, generating information both direction and level throughout genome. The...
Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. To gain comprehensive understanding of the roles Spt6, we performed genome-wide analyses transcription, chromatin structure, modifications in Schizosaccharomyces pombe spt6 mutant. Our results demonstrate dramatic changes transcription structure mutant, including elevated antisense transcripts at >70% all genes general loss +1 nucleosome. Furthermore,...
The SAGA complex is a conserved multifunctional coactivator known to play broad roles in eukaryotic transcription. To gain new insights into its functions, we performed biochemical and genetic analyses of the fission yeast, Schizosaccharomyces pombe . Purification S. showed that subunit composition identical Saccharomyces cerevisiae Analysis mutants revealed has two opposing regulating sexual differentiation. First, nutrient-rich conditions, histone acetyltransferase Gcn5 represses ste11 + ,...