A5052653700- Gene Regulatory Network Analysis
- Fungal and yeast genetics research
- Bioinformatics and Genomic Networks
- Neuroblastoma Research and Treatments
- Genomics and Chromatin Dynamics
- Cell Image Analysis Techniques
- Pluripotent Stem Cells Research
- Machine Learning in Bioinformatics
- Protein Structure and Dynamics
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Advanced Chemical Sensor Technologies
- Genetics, Aging, and Longevity in Model Organisms
- RNA and protein synthesis mechanisms
- Spectroscopy and Chemometric Analyses
- Chromatin Remodeling and Cancer
- Gaussian Processes and Bayesian Inference
- vaccines and immunoinformatics approaches
- RNA Research and Splicing
- Metabolomics and Mass Spectrometry Studies
- Microbial Metabolic Engineering and Bioproduction
- SARS-CoV-2 and COVID-19 Research
- Advanced Proteomics Techniques and Applications
St. Anna Children's Cancer Research Institute
2021-2024
St Anna Children's Hospital
2021-2024
University of Edinburgh
2016-2022
Community College of Rhode Island
2022
Wellcome Centre for Cell Biology
2016-2017
Institut de Biologie systémique et synthétique
2017
CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified nonsynonymous mutations MHC-I-restricted epitopes after deep sequencing of 747 isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding a cell-free vitro assay. Reduced mutant was associated with decreased proliferation, IFN-γ production cytotoxic activity cells isolated from HLA-matched patients. Single RNA ex vivo expanded, tetramer-sorted patients further...
Abstract Often the time derivative of a measured variable is as much interest itself. For growing population biological cells, for example, population’s growth rate typically more important than its size. Here we introduce non-parametric method to infer first and second derivatives function from time-series data. Our approach based on Gaussian processes applies wide range In tests, at least accurate others, but has several advantages: it estimates errors both in inference any summary...
Abstract Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to tumourigenesis due a lack of suitable models. Here we employ female human stem cell (hESC) differentiation and single-cell transcriptome epigenome analysis assess the effects chromosome 17q/1q gains, are prevalent in embryonal tumour neuroblastoma (NB). We show that impair specification trunk neural crest (NC) cells...
Improving in one aspect of a task can undermine performance another, but how such opposing demands play out single cells and impact on fitness is mostly unknown. Here we study budding yeast dynamic environments hyperosmotic stress show the corresponding signalling network increases cellular survival both by assigning requirements high response speed accuracy to two separate input pathways having these interact converge Hog1, p38 MAP kinase. Cells with only less accurate, reflex-like pathway...
A prime goal of regenerative medicine is to replace dysfunctional cells in the body. To design protocols for producing target laboratory, one may need consider exponentially large combinations culture components. Here, we investigated potential iteratively approximating phenotype by quantifying distance between chromatin profiles (ATAC-seq) differentiating vitro and their in-vivo counterparts. We tested this approach on well-studied generation erythroblasts from haematopoietic stem cells,...
Packaging of DNA into condensed chromosomes during mitosis is essential for the faithful segregation genome daughter nuclei. Although structure and composition mitotic have been studied over 30 years, these aspects are yet to be fully elucidated. Here, we used stable isotope labeling with amino acids in cell culture compare proteomes isolated from lines harboring conditional knockouts members condensin (SMC2, CAP-H, CAP-D3), cohesin (Scc1/Rad21), SMC5/6 (SMC5) complexes. Our analysis...
Ever-increasing numbers of quantitative proteomics data sets constitute an underexploited resource for investigating protein function. Multiprotein complexes often follow consistent trends in these experiments, which could provide insights about their biology. Yet, as more experiments are considered, a complex’s signature may become conditional and less identifiable. Previously we successfully distinguished the general proteomic genuine chromosomal proteins from hitchhikers using Random...
Eukaryotic genomes often encode multiple transporters for the same nutrient. For example, budding yeast has 17 hexose (HXTs), all of which potentially transport glucose. Using mathematical modelling, we show that use either facilitated diffusion or symport can have a rate-affinity tradeoff, where an increase in maximal rate decreases transporter’s apparent affinity. These changes affect import flux non-monotonically, and given concentration extracellular nutrient there is one transporter,...
Abstract Often the time-derivative of a measured variable is as much interest itself. For growing population biological cells, for example, population's growth rate typically more important than its size. Here we introduce non-parametric method to infer first and second time-derivatives function time from time-series data. Our approach based on established properties Gaussian processes therefore applies wide range In tests, at least accurate others, but has several advantages: it estimates...
The large and ever-increasing numbers of quantitative proteomics datasets constitute a currently underexploited resource for drawing biological insights on proteins their functions. Multiple observations by different laboratories indicate that protein complexes often follow consistent trends. However, proteomic data is noisy incomplete − members complex may correlate only in fraction all experiments, or not be observed experiments. Inclusion potentially uninformative hence imposes the risk...
Summary A common cellular task is to match gene expression dynamically a range of concentrations regulatory molecule. Studying glucose transport in budding yeast, we determine mechanistically how such matching occurs for seven hexose transporters. By combining time-lapse microscopy with mathematical modelling, find that levels transporters are history-dependent and regulated by push-pull system comprising two types repressors. Repression these varies opposite ways, not only matches the their...
Abstract Early childhood malignancies are driven by sparse genetic aberrations in oncogenes that often co-occur with large copy number variants (CNVs). The combination of these mutations is thought to transform developmentally pliant embryonic cells initiate tumorigenesis. However, the mechanistic interactions between CNVs, oncogenes, and differentiation have not been systematically studied due several obstacles: (i) CNVs cannot be engineered efficiently yet; (ii) transient progenitors...
Abstract Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to tumourigenesis due a lack of suitable models. Here we employ female human stem cell (hESC) differentiation and single-cell transcriptome epigenome analysis assess the effects chromosome 17q/1q gains, are prevalent in embryonal tumour neuroblastoma (NB). We show that impair specification trunk neural crest (NC) cells...