A5055093602- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Extracellular vesicles in disease
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Peptidase Inhibition and Analysis
- Phosphodiesterase function and regulation
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Mosquito-borne diseases and control
- Endoplasmic Reticulum Stress and Disease
- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Protein Kinase Regulation and GTPase Signaling
- Immunotherapy and Immune Responses
- PARP inhibition in cancer therapy
- Influenza Virus Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Fungal and yeast genetics research
- Gout, Hyperuricemia, Uric Acid
- Cancer Genomics and Diagnostics
- Insect symbiosis and bacterial influences
- Complement system in diseases
University of Oxford
2014-2024
Discovery Institute
2024
Science Oxford
2024
Digital Proteomics (United States)
2021
University of Cambridge
2004-2013
Harvard University
2012
The University of Texas Southwestern Medical Center
2012
University of Toronto
2012
A challenging task in the study of secretory pathway is identification and localization new proteins to increase our understanding functions different organelles. Previous proteomic studies endomembrane system have been hindered by contaminating proteins, making it impossible assign Here we used organelle isotope tagging technique conjunction with tags for relative absolute quantitation 2D liquid chromatography simultaneous assignment multiple subcellular compartments. With this approach,...
Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying severity in an integrated comparison influenza sepsis versus healthy volunteers. identify signatures correlates host response. Hallmarks disease involved cells, their inflammatory mediators networks, including progenitor cells myeloid lymphocyte subsets, features the repertoire,...
Highlights•A quarter of the RBPome changes upon SINV infection•Alterations in RBP activity are largely explained by RNA availability•Altered RBPs crucial for viral infection efficacy•GEMIN5 binds to 5′ end RNAs and regulates gene expressionSummaryThe compendium RNA-binding proteins (RBPs) has been greatly expanded development RNA-interactome capture (RIC). However, it remained unknown if complement response environmental perturbations whether these rearrangements important. To answer...
Abstract Background Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive at the transcriptional, proteomic metabolic levels under defined controlled conditions are currently lacking. Results Metabolic control analysis is being exploited in systems biology study eukaryotic cell. Using chemostat culture, we measured impact changes flux (growth rate) transcriptome, proteome,...
Tregs can adopt a catabolic metabolic program with increased capacity for fatty acid oxidation–fueled oxidative phosphorylation (OXPHOS). It is unclear why this form of metabolism favored in and, more specifically, whether represents an adaptation to the environment and developmental cues or "hardwired" by Foxp3. Here we show, using analysis unbiased mass spectroscopy–based proteomics approach, that Foxp3 both necessary sufficient Treg-increased respiratory Tregs' ability utilize acids fuel...
Abstract Wolbachia are intracellular maternally inherited bacteria that can spread through insect populations and block virus transmission by mosquitoes, providing an important approach to dengue control. To better understand the mechanisms of inhibition, we here perform proteomic quantification effects in Aedes aegypti mosquito cells midgut. Perturbations observed vesicular trafficking, lipid metabolism endoplasmic reticulum could impact viral entry replication. Wolbachia- infected display...
Clathrin-coated vesicles (CCVs) facilitate the transport of cargo between trans-Golgi network, endosomes, and plasma membrane. This study presents first comparative proteomics investigation CCVs. A CCV-enriched fraction was isolated from HeLa cells a “mock CCV” clathrin-depleted cells. We used combination 2D difference gel electrophoresis isobaric tags for relative absolute quantification (iTRAQ) in conjunction with mass spectrometry to analyze compare two fractions. In total, 63 bona fide...
Exosomes are small extracellular vesicles, approximately 50 nm in diameter, derived from the endocytic pathway and released by a variety of cell types. Recent data indicate spectrum exosomal functions, including RNA transfer, antigen presentation, modulation apoptosis, shedding obsolete protein. all nephron segments also present human urine, where their function is unknown. Although one report suggested vitro uptake exosomes renal cortical collecting duct cells, most studies urinary have...
Protein phosphorylation is a common post-translational modification in eukaryotic cells and has wide range of functional effects. Here, we used mass spectrometry to search for phosphorylated residues all the proteins influenza A B viruses – best our knowledge, first time such comprehensive approach been applied virus. We identified 36 novel sites, as well confirming 3 previously-identified sites. N-terminal processing ubiquitination viral was also detected. Phosphorylation detected...
The endoribonuclease Dicer is a key component of the human RNA interference pathway and known for its role in cytoplasmic microRNA production. Recent findings suggest that noncanonical generates small noncoding to mediate DNA damage response (DDR). Here, we show phosphorylated platform-Piwi/Argonaute/Zwille-connector helix cassette (S1016) upon induction damage. Phosphorylated (p-Dicer) accumulates nucleus recruited double-strand breaks. We further demonstrate turnover damage-induced...
Significance Partner and localiser of BRCA2 (PALB2) is a breast cancer susceptibility gene, the role its product in repairing broken chromosomes has been extensively described. However, fraction PALB2 also found on intact chromosomes, it unknown how why associates with undamaged chromatin. In this study, we establish that histone binding protein MRG15 major interaction partner plays key tethering to active genes. Failure interact leads accumulation DNA stress at genes chromosome instability...
Abstract CDK9 is a kinase critical for the productive transcription of protein‐coding genes by RNA polymerase II (pol II). As part P‐TEFb, phosphorylates carboxyl‐terminal domain (CTD) pol and elongation factors, which allows to elongate past early checkpoint (EEC) encountered soon after initiation. We show that, in addition halting at EEC, loss activity causes premature termination across last exon, polyadenylation factors from chromatin, nascent transcripts. Inhibition phosphatase PP2A...
A major challenge in eukaryotic cell biology is to understand the roles of individual proteins and subcellular compartments which they reside. Here, we use localization organelle by isotope tagging technique complete first proteomic analysis organelles DT40 lymphocyte line. This line emerging as an important research tool because ease with gene knockouts can be generated. We identify 1090 through preparations enriched for integral membrane or soluble peripherally associated localize 223...
ABSTRACT Leptospirosis is a life-threatening and emerging zoonotic disease with worldwide annual occurrence of more than 1 million cases. caused by spirochetes belonging to the genus Leptospira . The mechanisms manifestation in host remain elusive, roles leptospiral exoproteins these processes have yet be determined. Our aim this study was assess composition quantity pathogenic interrogans construe how proteins contribute pathogenesis. Label-free quantitative mass spectrometry obtained from...
Signaling by cAMP is organized in multiple distinct subcellular nanodomains regulated cAMP-hydrolyzing PDEs (phosphodiesterases). Cardiac β-adrenergic signaling has served as the prototypical system to elucidate compartmentalization. Although studies cardiac myocytes have provided an understanding of location and properties a handful compartments, overall view cellular landscape missing.
KRAS is a proto-oncogene encoding small GTPase. Mutations contribute to ∼30% of human solid tumours, including lung adenocarcinoma, pancreatic, and colorectal carcinomas. Most activating mutations interfere with GTP hydrolysis, essential for its role as molecular switch, leading alterations in their environment oncogenic signalling. However, the precise signalling cascades these affect are poorly understood. Here, APEX2 proximity labelling was used profile WT, G12D, G13D, Q61H-activating...
Abstract Persistent pathogens have evolved to avoid elimination by the mammalian immune system including mechanisms evade complement. Infections with African trypanosomes can persist for years and cause human animal disease throughout sub-Saharan Africa. It is not known how limit action of alternative complement pathway. Here we identify an trypanosome receptor factor H, a negative regulator Structural studies show binds ligand, leaving inhibitory domains H free inactivate C3b deposited on...
<title>Abstract</title> The developmentally dynamic stem cell-like subpopulation in cancers known as cancer cells (CSCs) metastasize efficiently, form new tumours, and are resistant to current therapeutics. Understanding the molecular mechanisms of state could help eliminate CSCs via novel therapeutic applications aggressive such pancreatic ductal adenocarcinoma (PDAC). Here, we performed a compound screen uncovering that inhibition Hypoxia-inducible factor prolyl hydroxylase 2 (PHD2)...
Extracellular vesicles (EVs) are proposed to play a role in the development of cardiovascular diseases (CVDs) and considered emerging markers CVDs. N-3 polyunsaturated fatty acids (PUFAs) abundant oily fish oil reported reduce CVD risk, but there has been little research date examining effects n-3 PUFAs on generation function EVs. The objective study was investigate supplementation number, EVs subjects with moderate risk A total 40 participants CVDs were supplemented capsules containing...
Abstract Background Serratia sp. ATCC 39006 (S39006) is a Gram-negative enterobacterium that virulent in plant and animal models. It produces red-pigmented trypyrrole secondary metabolite, prodigiosin (Pig), carbapenem antibiotic (Car), as well the exoenzymes, pectate lyase cellulase. Secondary metabolite production this strain controlled by complex regulatory network involving quorum sensing (QS). Hfq RsmA (two RNA binding proteins major post-transcriptional regulators of gene expression)...
Asparagine levels are reduced in patients with diabetes and alcoholism. A plausible mechanism is that aldehydes elevated these diseases react the N-terminal cysteine of asparagine synthetase B, so inhibiting production.
Abstract CD8 + T lymphocytes play vital roles in killing infected or deranged host cells, recruiting innate immune and regulating other aspects of responses. Like any cell, cells also produce extracellular particles. These include vesicles (EVs) non‐vesicular particles (NVEPs). cell‐derived EVs are proposed to mediate cell‐to‐cell signalling, especially the context inflammatory responses, autoimmunity, infectious diseases. supramolecular attack (SMAPs), which same size range as a component...