A5088655120- Glycosylation and Glycoproteins Research
- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Milk Quality and Mastitis in Dairy Cows
- Infant Nutrition and Health
- Microtubule and mitosis dynamics
- Animal Genetics and Reproduction
- Immune Cell Function and Interaction
- Immune cells in cancer
- Immune Response and Inflammation
- Polyamine Metabolism and Applications
- Genetic and phenotypic traits in livestock
- Advanced Proteomics Techniques and Applications
- Animal health and immunology
- Fungal and yeast genetics research
- Genomics and Chromatin Dynamics
- Cell Image Analysis Techniques
- Synthesis and Catalytic Reactions
- Invertebrate Immune Response Mechanisms
- Biochemical and Molecular Research
- Celiac Disease Research and Management
- Hormonal and reproductive studies
- Parkinson's Disease Mechanisms and Treatments
- Biotin and Related Studies
- Microbial Natural Products and Biosynthesis
University of Edinburgh
2017-2024
Wellcome Centre for Cell Biology
2020-2024
University of Auckland
2006-2022
Centre for Immunity, Infection and Evolution
2021
Brewster Place
2018
MRC Protein Phosphorylation and Ubiquitylation Unit
2014
University of Dundee
2013-2014
Mutations in PINK1 and Parkin are associated with early-onset Parkinson's disease. We recently discovered that phosphorylates at serine65 (Ser 65 ) within its Ubl domain, leading to activation a substrate-free activity assay. now demonstrate the critical requirement of Ser phosphorylation for substrate ubiquitylation through elaboration novel vitro E3 ligase assay using full-length untagged putative substrate, mitochondrial GTPase Miro1. observe efficiently ubiquitylates Miro1 highly...
Abstract Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, often neglected. In present study, we have shown that ARDS patients were hypoxemic monocytopenic within first 48 h ventilation. Monocytopenia was also observed in mouse models hypoxic lung injury, which hypoxemia drove suppression type I interferon signaling bone marrow....
The cell cycle is ordered by a controlled network of kinases and phosphatases. To generate gametes via meiosis, two distinct sequential chromosome segregation events occur without an intervening S phase. How canonical controls are modified for meiosis not well understood. Here, using highly synchronous budding yeast populations, we reveal how the global proteome phosphoproteome change during meiotic divisions. While protein abundance changes limited to key regulators, dynamic phosphorylation...
Abstract Human colostrum is an important source of protective, nutritional and developmental factors for the newborn. We have investigated low abundance proteins in aqueous phase human colostrum, after depletion major secretory IgA, lactoferrin, alpha‐lactalbumin HSA by immunoabsorption, using 2‐D LC gel‐based proteomic methods. One hundred fifty‐one were identified, 83 which not been previously reported or milk. This first comprehensive analysis produced during 48 h lactation.
HIF1A (hypoxia-inducible factor 1α) is the master regulator of cellular response to hypoxia and implicated in cancer progression. Whereas regulation protein oxygen well characterized, less known about fate mRNA. In present study, we have identified pseudo-DUB (deubiquitinating enzyme)/deadenylase USP52 (ubiquitin-specific protease 52)/PAN2 [poly(A) nuclease 2] as an important HIF1A-mediated hypoxic response. Depletion reduced mRNA levels resulted expression HIF1A-regulated targets due a...
Previous investigations of bovine seminal plasma (BSP) have revealed the identities three major proteins, BSP-PDC109, BSP-A3 and BSP-30 kDa, which together constitute about half total protein, as well 30 minor proteins. Analyses BSP by 2-DE 250 protein spots, suggesting that much proteome remains undescribed. In this study, has been analyzed 2-D LC-based SDS-PAGE-based proteomic methods. Ninety-nine proteins were identified, including 49 not previously described in any species.
Control of mRNA translation adjusts protein production rapidly and facilitates local cellular responses to environmental conditions. Traditionally initiation is considered be a major translational control point, however, peptide elongation also important. Here we show that the function factor, eIF5a, regulated dynamically in naïve CD8
Comprehensive proteome analysis of rare cell phenotypes remains a significant challenge. We report method for low number MS-based proteomics using protease digestion mildly formaldehyde-fixed cells in cellulo, which we call the "in-cell digest." combined this with averaged MS1 precursor library matching to quantitatively characterize proteomes from numbers human lymphoblasts. About 4500 proteins were detected 2000 cells, and 2500 quantitated 200 The ease sample processing high sensitivity...
Meiosis creates genetic diversity by recombination and segregation of chromosomes. The synaptonemal complex assembles during meiotic prophase I assists faithful exchanges between homologous chromosomes, but how its assembly/disassembly is regulated remains to be understood. Here, we report two major posttranslational modifications, phosphorylation ubiquitination, cooperate promote assembly. We found that the ubiquitin ligase SCF important for assembly maintenance in Drosophila female...
TamA is the adenylating enzyme that selects and activates fatty acids for tambjamine biosynthesis.
Milk samples from 10,641 dairy cattle were screened by a mass spectrometry method for extreme concentrations of the A or B isoforms whey protein, β-lactoglobulin (BLG), to identify causative genetic variation driving changes in BLG concentration.A cohort cows, single sire family, was identified that produced milk containing low concentration protein isoform. genome-wide association study (GWAS) isoform AB heterozygous detected group highly significant nucleotide polymorphisms (SNPs) within...
The aim of this study was to determine a genetic basis for IgA concentration in milk Bos taurus. We used Holstein-Friesian x Jersey F2 crossbred pedigree undertake genome-wide search QTL influencing and yield colostrum milk. identified single significant on chromosome 16, maximising at 4.8 Mbp. polymeric immunoglobulin receptor gene (PIGR) within the confidence interval QTL. In addition, mRNA expression analysis revealed liver PIGR mapping same locus as quantitative trait locus. Sequencing...
We use mass spectrometry analysis and molecular modelling to show the established antimicrobial inhibitor 4,5-dichloro-1,2-dithiol-3-one (HR45) acts by forming a covalent adduct with target β-ketoacyl-ACP synthase III (FabH). The 5-chloro substituent directs attack of essential active site thiol (C112) via Michael-type addition elimination reaction mechanism.
Isotope labels are frequently used tools to track metabolites through complex biochemical pathways and discern the mechanisms of enzyme-catalyzed reactions. Isotopically labeled l-serine is often monitor activity first enzyme in sphingolipid biosynthesis, serine palmitoyltransferase (SPT), as well labeling downstream cellular metabolites. Intrigued by effect that isotope may be having on SPT catalysis, we characterized impact different isotopologues catalytic recombinant isozymes from humans...
Abstract The cell cycle is ordered by a controlled network of kinases and phosphatases. To generate gametes via meiosis, two distinct sequential chromosome segregation events occur without an intervening S phase. How canonical controls are modified for meiosis not well understood. Here, using highly synchronous budding yeast populations, we reveal how the global proteome phosphoproteome changes during meiotic divisions. While protein abundance limited to key regulators, dynamic...
Abstract Acute Respiratory Distress Syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, has no cure. Hypoxemia is a defining feature, yet its impact on inflammation often neglected. Patients with ARDS are monocytopenic early in the onset disease. Endotoxin Streptococcus pneumoniae acute lung injury (ALI) context hypoxia replicates this finding, through hypoxia-driven suppression type I interferon signalling. This results failed monocyte-derived interstitial...
Abstract Translational control adjusts protein production rapidly and facilitates local cellular responses to environmental conditions. Translation can be regulated through sequestration of mRNAs by regulatory proteins or RNAs, but also the availability ribosomes translation factors which enable initiation elongation nascent polypeptides. Traditionally mRNA has been considered a major translational point, however, peptide play role. Here we show that post-translational modification factor,...