A5065696246- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Immune Cell Function and Interaction
- Advanced biosensing and bioanalysis techniques
- RNA regulation and disease
- interferon and immune responses
- Cholesterol and Lipid Metabolism
- Virus-based gene therapy research
- Gene Regulatory Network Analysis
- Advanced Biosensing Techniques and Applications
- Sepsis Diagnosis and Treatment
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- Microbial Metabolic Engineering and Bioproduction
- Reproductive System and Pregnancy
- Neonatal and Maternal Infections
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- HIV Research and Treatment
- Genetics, Bioinformatics, and Biomedical Research
- Computational Drug Discovery Methods
- Bacterial Identification and Susceptibility Testing
- Animal Virus Infections Studies
Cardiff University
2019-2024
University of Bristol
2024
Center for Systems Biology
2021
University of Edinburgh
2011-2020
Centre for Immunity, Infection and Evolution
2020
Pathway
2013-2016
Ludwig-Maximilians-Universität München
2013
Addenbrooke's Hospital
2013
University of Duisburg-Essen
2013
Barcelona Biomedical Research Park
2013
RNA levels in a cell are determined by the relative rates of synthesis and decay. State-of-the-art transcriptional analyses only employ total cellular RNA. Therefore, changes cannot be attributed to or decay, temporal resolution is poor. Recently, it was reported that newly transcribed can biosynthetically labeled for 1-2 h using thiolated nucleosides, purified from subjected microarray analysis. However, order study signaling events at molecular level, analysis occurring within minutes...
The human cytomegalovirus (HCMV) genomic unique short (US) region encodes a family of homologous genes essential for the inhibition major histocompatibility complex (MHC) class I-mediated antigen presentation during viral infection. Here we show that US3, only immediate early (IE) gene within US region, an endoplasmic reticulum-resident glycoprotein prevents intracellular transport MHC I molecules. In contrast to rapid degradation newly synthesized heavy chains mediated by product US11,...
Upon infection, our immune cells produce a small protein called interferon, which in turn signals protective response through series of biochemical reactions that involves lowering the cells' ability to make cholesterol by targeting gene essential for controlling pathway metabolism.
Severe infectious disease in children may be a manifestation of primary immunodeficiency. These genetic disorders represent important experiments nature with the capacity to elucidate nonredundant mechanisms human immunity. We hypothesized that defect innate antiviral immunity was responsible for unusually severe viral illness two siblings; proband developed disseminated vaccine strain measles following routine immunization, whereas an infant brother died after 2-d febrile from unknown...
Mechanistic studies have established a biological role of sterol metabolism in infection and immunity with clinical data linking deranged cholesterol during sepsis poorer outcomes. In this systematic review we assess the relationship between biomarkers homeostasis mortality critical illness.
Monocytes are one of the predominant cell types in peripheral blood that infected by human cytomegalovirus (HCMV). Although virus can be detected these cells vivo, HCMV replication cultured monocytes has been unsuccessful. In this study, we demonstrate efficient monocytes. permissiveness was dependent on nonadherent cell-induced stimulation monocyte, with subsequent morphological differentiation into macrophages. Approximately 40% were immunofluorescent staining both immediate-early and late...
The genus Coccolithovirus is a recently discovered group of viruses that infect the globally important marine calcifying microalga Emiliania huxleyi . Among 472 predicted genes 407,339–base pair genome are variety unexpected genes, most notably those involved in biosynthesis ceramide, sphingolipid known to induce apoptosis. Uniquely for algal viruses, it also contains six RNA polymerase subunits and novel promoter, suggesting this virus encodes its own transcription machinery. Microarray...
ABSTRACT We describe, for the first time, generation of a viral DNA chip simultaneous expression measurements nearly all known open reading frames (ORFs) in largest member herpesvirus family, human cytomegalovirus (HCMV). In this study, an HCMV was fabricated and used to characterize temporal class gene expression. The is composed microarrays prepared by robotic deposition oligonucleotides on glass ORFs genome. Viral monitored hybridization oligonucleotide with fluorescently labelled cDNAs...
The transcription factor Sox1 is the earliest and most specific known marker for mammalian neural progenitors. During fetal development, expressed by proliferating progenitor cells throughout central nervous system in no tissue but lens. We generated a reporter mouse line which egfp inserted into locus. GFP animals faithfully recapitulate expression of endogenous gene. have used to purify neuroepithelial fluorescence-activated cell sorting from embryonic day 10.5 embryos. RNAs prepared GFP+...
trans activation of promoters by viral regulatory proteins provides a useful tool to study coordinate control gene expression. Immediate-early (IE) regions 1 and 2 human cytomegalovirus (CMV) code for series that originate from differentially spliced mRNAs. These IE are proposed regulate the temporal expression genome. To examine structure function proteins, we used linker insertion mutagenesis region as well cDNA vector cloning abundant We showed IE1 IE2 CMV exhibit promoter-specific...
A prostaglandin barrier to inflammation Blood-borne bacterial infections and severe trauma can send the immune system into overdrive, causing it pump out inflammatory mediators, sometimes at lethal doses. Duffin et al. now report on a role for prostaglandins in keeping systemic check. Systemic correlates with decreased production of E2 (PGE2). Blocking PGE2 signaling mice led associated translocation gut bacteria. acts innate lymphoid cells, which produce interleukin-22, secreted protein...
Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses shows surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition lymphoid responses. Innate immune-negative feedback opposes innate activation while suppression T-cell co-stimulation is coincident selective upregulation CD85...
Abstract The mechanisms controlling CD4 + T cell switching from an effector to anti-inflammatory (IL-10 ) phenotype play important role in the persistence of chronic inflammatory diseases. Here, we identify cholesterol biosynthesis pathway as a key regulator this process. Pathway analysis cultured cytokine-producing human cells reveals significant association between IL-10 and metabolism gene expression. Inhibition with atorvastatin or 25-hydroxycholesterol during IFNγ shows specific block...
In invertebrates, small interfering RNAs are at the vanguard of cell-autonomous antiviral immunity. contrast, mechanisms initiated by interferon (IFN) signaling predominate in mammals. Whilst mammalian IFN-induced miRNA known to inhibit specific viruses, it is not whether host-directed microRNAs, downstream IFN-signaling, have a role mediating broad resistance. By performing an integrative, systematic, global analysis RNA turnover utilizing 4-thiouridine labeling newly transcribed and...
Rationale: Pooling data from multiple cohorts and extending the time frame across childhood should minimize study-specific effects, enabling better characterization of wheezing. Objectives: To analyze wheezing patterns early to adolescence using combined five birth cohorts. Methods: We used latent class analysis derive wheeze phenotypes among 7,719 participants with complete report at periods. tested associations derived late asthma outcomes lung function, investigated uncertainty in...
Abstract Oxylipins are potent biological mediators requiring strict control, but how they removed en masse during infection and inflammation is unknown. Here we show that lipopolysaccharide (LPS) dynamically enhances oxylipin removal via mitochondrial β-oxidation. Specifically, genetic or pharmacological targeting of carnitine palmitoyl transferase 1 (CPT1), a importer fatty acids, reveal many oxylipins by this protein in vitro vivo. Using stable isotope-tracing lipidomics, find...
In vitro PA28 binds and activates proteasomes . It is shown here that mice with a disrupted PA28b gene lack PA28a polypeptides, demonstrating functions as hetero-oligomer in vivo. Processing of antigenic epitopes derived from exogenous or endogenous antigens altered –/– mice. Cytotoxic T lymphocyte responses are impaired, assembly immunoproteasomes greatly inhibited lacking PA28. These results show necessary for immunoproteasome required efficient antigen processing, thus the importance...