A5012730233- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Metabolomics and Mass Spectrometry Studies
- RNA regulation and disease
- Single-cell and spatial transcriptomics
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Satellite Image Processing and Photogrammetry
- Pluripotent Stem Cells Research
- Advanced Algorithms and Applications
- interferon and immune responses
- Glycosylation and Glycoproteins Research
- Spacecraft and Cryogenic Technologies
- scientometrics and bibliometrics research
- Sensor Technology and Measurement Systems
- MicroRNA in disease regulation
King Abdullah University of Science and Technology
2019-2025
University of Dundee
2013-2022
Bruker (United Kingdom)
2018
Cell and Gene Therapy Catapult
2013
Abstract Recent developments in stem cell biology have enabled the study of fate decisions early human development that are impossible to vivo. However, understanding how varies across individuals and, particular, influence common genetic variants during this process has not been characterised. Here, we exploit iPS lines from 125 donors, a pooled experimental design, and single-cell RNA-sequencing population variation endoderm differentiation. We identify molecular markers predictive...
Multiplexing strategies for large-scale proteomic analyses have become increasingly prevalent, tandem mass tags (TMT) in particular. Here we used a large iPSC experiment with twenty-four 10-plex TMT batches to evaluate the effect of integrating multiple within single analysis. We identified significant inflation rate protein missing values as are integrated and show that this pattern is aggravated at peptide level. also without normalization address batch effects, high precision quantitation...
Constitutive heterochromatin is responsible for genome repression of DNA enriched in repetitive sequences, telomeres, and centromeres. During physiological pathological premature aging, homeostasis profoundly compromised. Here, we showed that LINE-1 ( Long Interspersed Nuclear Element-1; L1 ) RNA accumulation was an early event both typical atypical human progeroid syndromes. negatively regulated the enzymatic activity histone-lysine N -methyltransferase SUV39H1 (suppression variegation 3-9...
PHD1 belongs to the family of prolyl-4-hydroxylases (PHDs) that is responsible for posttranslational modification prolines on specific target proteins. Because PHD activity sensitive oxygen levels and certain byproducts tricarboxylic acid cycle, PHDs act as sensors cell's metabolic state. Here, we identify a critical molecular link between sensing cell-cycle control. We show function required centrosome duplication maturation through component Cep192. Importantly, also primary cilia...
Human disease phenotypes are driven primarily by alterations in protein expression and/or function. To date, relatively little is known about the variability of human proteome populations and how this relates to mRNA loci. Here, we present first comprehensive proteomic analysis induced pluripotent stem cells (iPSC), a key cell type for modelling, analysing 202 iPSC lines derived from 151 donors, with integrated transcriptome genomic sequence data same lines. We characterised major genetic...
Abstract Arabidopsis is an important model organism and the first plant with its genome completely sequenced. Knowledge from studying this species has either direct or indirect applications for agriculture human health. Quantitative proteomics by data-independent acquisition mass spectrometry (SWATH/DIA-MS) was recently developed considered as a high-throughput, massively parallel targeted approach accurate proteome quantification. In approach, high-quality comprehensive spectral library...
X chromosome inactivation (XCI) is a dosage compensation mechanism in female mammals whereby transcription from one repressed. Analysis of human induced pluripotent stem cells (iPSCs) derived donors identified that low levels XIST RNA correlated strongly with erosion XCI. Proteomic analysis, sequencing (RNA-seq), and polysome profiling showed XCI resulted amplified protein expression X-linked genes, providing proteomic characterization skewed compensation. Increased was also detected...
We introduce here a novel approach, termed time-segmented acquisition (Seg), to enhance the identification of peptides and proteins in trapped ion mobility spectrometry (TIMS)-time-of-flight (TOF) mass spectrometry. Our method exploits positive correlation between values reversed-phase liquid chromatography (LC) retention time improve separation resolution. By dividing LC into multiple segments applying segment-specific narrower range within TIMS tunnel, we achieved better higher resolution...
Proteomics studies typically analyze proteins at a population level, using extracts prepared from tens of thousands to millions cells. The resulting measurements correspond average values across the cell and can mask considerable variation in protein expression function between individual cells or organisms. Here, we report development micro‐proteomics for analysis Caenorhabditis elegans , eukaryote composed 959 somatic ∼1500 germ cells, measuring worm proteome single organism level depth...
Abstract Membraneless organelles are sites for RNA biology including small non-coding (ncRNA) mediated gene silencing. How ncRNAs utilise phase separated environments their function is unclear. We investigated how the PIWI-interacting (piRNA) pathway engages with membraneless organelle P granule in Caenorhabditis elegans . Proteomic analysis of PIWI protein PRG-1 reveals an interaction constitutive DEPS-1. DEPS-1 not required piRNA biogenesis but piRNA-dependent silencing: deps-1 mutants...
Abstract Induced pluripotent stem cell (iPSC) technology has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterisation many existing iPSC lines limits their use for research therapy. Here, we describe the systematic generation, genotyping phenotyping 522 open access iPSCs derived from 189 healthy male female individuals as part Human Pluripotent Stem Cells Initiative (HipSci: http://www.hipsci.org ). Our study provides...
PHD1 (also known as EGLN2) belongs to a family of prolyl hydroxylases (PHDs) that are involved in the control cellular response hypoxia. is also able regulate mitotic progression through regulation crucial centrosomal protein Cep192, establishing link between oxygen-sensing and cell cycle machinery. Here, we demonstrate phosphorylated by CDK2, CDK4 CDK6 at S130. This phosphorylation fluctuates with can be induced oncogenic activation. Functionally, leads increased induction hypoxia-inducible...
We have identified the human FMN2 gene as a novel target regulated by induction of p14ARF and multiple other stress responses, including DNA damage hypoxia, which in common activation cell cycle arrest. showed that increased expression following is caused, at transcriptional level, relief repression RelA E2F1, which, under non-induced conditions, bind promoter. Increased protein levels promote arrest inhibiting degradation p21, our data show control p21 stability key part mechanism regulates...
We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions sequence complementarity with the mRNA target. Here we characterise use snoMEN vectors target micro RNA primary transcripts. document specific miR21 in HeLa cells plasmid expressing miR21-targeted RNAs and show this induces apoptosis. Knock-down is dependent on presence complementary sequences vector induction...
Abstract Asymmetric cell divisions are required for cellular diversity and defects can lead to altered daughter fates numbers. In a genetic screen C . elegans mutants with in dopaminergic head neuron specification or differentiation, we isolated new allele of the transcription factor HAM-1 [HSN (Hermaphrodite-Specific Neurons) Abnormal Migration]. Loss both its target, kinase PIG-1 [PAR-1(I)-like Gene], leads abnormal We identified discrete relationships between ham - 1 , pig apoptosis...
Data independent acquisition-mass spectrometry (DIA-MS) is becoming widely utilised for robust and accurate quantification of samples in quantitative proteomics. Here, we describe the systematic evaluation effects DIA precursor mass range on total protein identification quantification. We show that a narrow precursors (~250 m/z) DIA-MS enables higher number identifications. Subsequent application with (from 400 to 650 an Arabidopsis sample spike-in known proteins identified 34.7% more than...
Despite many recent advances in instrumentation, the sheer complexity of biological samples remains a major challenge large-scale proteomics experiments, reflecting both large number protein isoforms and wide dynamic range their expression levels. However, while levels for different components proteome is estimated to be ∼107–8, equivalent LC–MS currently limited ∼106. Sample pre-fractionation has therefore become routinely used reduce sample during MS analysis thus alleviate problem ion...
Abstract Realising the potential of human induced pluripotent stem cell (iPSC) technology for drug discovery, disease modelling and therapy requires an understanding variability across iPSC lines. While previous studies have characterized iPS lines genetically transcriptionally, little is known about proteome. Here, we present first comprehensive proteomic dataset, analysing 202 derived from 151 donors. We characterise major genetic determinants affecting proteome transcriptome variation...
Chromatin marks are recognized by distinct binding modules, many of which embedded in multidomain proteins. How the different functionalities such complex chromatin modulators regulated is often unclear. Here, we delineated interplay H3 amino terminus– and K9me-binding activities hUHRF1 protein. We show that phosphoinositide PI5P interacts simultaneously with two distant flexible linker regions connecting domains hUHRF1. The dependent on both, polar head group, acyl part phospholipid induces...