A5016842515- Viral Infections and Immunology Research
- Viral gastroenteritis research and epidemiology
- RNA and protein synthesis mechanisms
- Animal Virus Infections Studies
- RNA regulation and disease
- Endoplasmic Reticulum Stress and Disease
- Insect symbiosis and bacterial influences
- Carbohydrate Chemistry and Synthesis
- Bacteriophages and microbial interactions
- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- Mosquito-borne diseases and control
- Advanced Biosensing Techniques and Applications
- Lipid Membrane Structure and Behavior
- Viral Infections and Vectors
- Microbial infections and disease research
- Studies on Chitinases and Chitosanases
- Tissue Engineering and Regenerative Medicine
- American and British Literature Analysis
- Genomics and Phylogenetic Studies
- Photoreceptor and optogenetics research
- Protein purification and stability
University of Cambridge
1968-2024
Addenbrooke's Hospital
2020
Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by proteins in endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling investigate holistically transcriptional translational murine hepatitis virus (MHV), often as model for Betacoronavirus genus which recently emerged SARS-CoV-2 also belongs. found UPR be amongst most significantly up-regulated pathways MHV...
Sphingolipids are essential components of cellular membranes and defects in their synthesis or degradation cause severe human diseases. The efficient sphingolipids the lysosome requires lipid-binding saposin proteins hydrolytic enzymes. glycosphingolipid galactocerebroside is primary lipid component myelin sheath degraded by hydrolase β-galactocerebrosidase (GALC). This enzyme SapA for processing either these causes a neurodegenerative disorder, Krabbe disease. Here we present structure...
The arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses to the swine industry worldwide. Here we apply ribosome profiling (RiboSeq) parallel RNA sequencing (RNASeq) characterise transcriptome translatome of both species PRRSV analyse host response infection. We calculated programmed ribosomal frameshift (PRF) efficiency at sites on viral genome. This revealed nsp2 PRF site as second known example where temporally regulated frameshifting...
Enteroviruses comprise a large group of mammalian pathogens that often utilize two open reading frames (ORFs) to encode their proteins: the upstream protein (UP) and main polyprotein. In some enteroviruses, in addition canonical AUG (uAUG), there is another may represent an alternative initiation site. An analysis enterovirus sequences containing additional AUGs identified several clusters, including strains pathogenic Enterovirus alphacoxsackie E. coxsackiepol. Using ribosome profiling on...
Abstract Zika virus (ZIKV), an emerging mosquito-borne flavivirus, is associated with congenital neurological complications. Here, we investigate potential pathological correlates of gene expression in representative ZIKV strains through RNA sequencing and ribosome profiling. In addition to the single long polyprotein found all flaviviruses, identify translation unrecognised upstream open reading frames (uORFs) genomic 5′ region. Asian/American strains, ribosomes translate uORF1 uORF2,...
The 2A protein of Theiler's murine encephalomyelitis virus (TMEV) acts as a switch to stimulate programmed -1 ribosomal frameshifting (PRF) during infection. Here, we present the X-ray crystal structure TMEV and define how it recognises stimulatory RNA element. We demonstrate critical role for bases upstream originally predicted stem-loop, providing evidence pseudoknot-like conformation suggesting that recognition this pseudoknot by beta-shell proteins is conserved feature in cardioviruses....
Abstract Zika virus (ZIKV) is an emerging mosquito-borne flavivirus recently associated with congenital diseases and neurological complications. As for all flaviviruses, the ZIKV RNA genome expected to encode a single polyprotein enzymatic activities required viral replication. Here, we report discovery of multiple non-canonical open reading frames (ORFs) identified by ribosome profiling. In both mammalian insect cells infected Asian/American African strains, observed translation previously...
The International Virus Bioinformatics Meeting 2020 was originally planned to take place in Bern, Switzerland, March 2020. However, the COVID-19 pandemic put a spoke wheel of almost all conferences be held After moving conference 8–9 October 2020, we got hit by second wave and finally decided at short notice go fully online. On other hand, has made us even more aware importance accelerating research viral bioinformatics. Advances bioinformatics have led improved approaches investigate...
Beauty Dreams Georgia Cook (bio) She has a complex relationship with sleep. Sometimes she jokes that lacks the knack, and dreams are old, embittered lovers. As child, would toss turn until gray light of dawn crept across her bedroom carpet, tinging world silver. teenager, adopted habits night owl, trawling pubs clubs Central London pollution faded from orange to white filled bleary-eyed commuters. never wanted stop, dread lying sleepless in bed, staring at ceiling, haunted by everything but...
Abstract Sphingolipids are essential components of cellular membranes and defects in their synthesis or degradation cause severe human diseases. The efficient sphingolipids the lysosome requires lipid-binding saposin proteins hydrolytic enzymes. glycosphingolipid galactocerebroside is primary lipid component myelin sheath degraded by hydrolase β-galactocerebrosidase (GALC). This enzyme SapA for processing either these causes a neurodegenerative disorder, Krabbe disease. Here we present...
Abstract Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by proteins in endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling investigate holistically transcriptional translational murine hepatitis virus (MHV), often as model for Betacoronavirus genus which recently emerged SARS-CoV-2 also belongs. found UPR be amongst most significantly up-regulated pathways...
Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus of huge economic importance, infecting the porcine host leading to infertility, morbidity, mortality. Its genome contains a canonical −1 programmed ribosomal frameshift (PRF) site that facilitates expression viral replicase, second, non-canonical signal which induces both −2 PRF generate alternative forms non-structural polypeptide, nsp2. In contrast sites, at not stimulated by downstream secondary RNA structure,...
Abstract The 2A protein of Theiler’s murine encephalomyelitis virus (TMEV) acts as a switch to stimulate programmed −1 ribosomal frameshifting (PRF) during infection. Here we present the X-ray crystal structure TMEV and define how it recognises stimulatory RNA element. We demonstrate critical role for bases upstream originally predicted stem-loop, providing evidence pseudoknot-like conformation suggesting that recognition this pseudoknot by beta-shell proteins is conserved feature in...
Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus which causes significant economic losses to the swine industry worldwide. Here, we use ribosome profiling (RiboSeq) parallel RNA sequencing (RNASeq) characterise transcriptome translatome of both species PRRSV analyse host response infection. We quantified viral gene expression over a timecourse infection, calculated efficiency programmed ribosomal frameshifting (PRF) at sites on genome. At nsp2 frameshift...