A5082818097- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- RNA modifications and cancer
- Parasitic Infections and Diagnostics
- Bacteriophages and microbial interactions
- Neonatal and fetal brain pathology
- Fetal and Pediatric Neurological Disorders
- Genomics and Rare Diseases
- Polar Research and Ecology
- Evolution and Genetic Dynamics
- Physiological and biochemical adaptations
- Microbial Community Ecology and Physiology
- Enzyme Structure and Function
Newcastle University
2021-2024
Great Ormond Street Hospital
2022
University College London
2022
Abstract To conserve energy during starvation and stress, many organisms use hibernation factor proteins to inhibit protein synthesis protect their ribosomes from damage 1,2 . In bacteria, two families of factors have been described, but the low conservation these huge diversity species, habitats environmental stressors confounded discovery 3–6 Here, by combining cryogenic electron microscopy, genetics biochemistry, we identify Balon, a new in cold-adapted bacterium Psychrobacter urativorans...
Abstract The evolution of microbial parasites involves the counterplay between natural selection forcing to improve and genetic drifts lose genes accumulate deleterious mutations. Here, understand how this occurs at scale individual macromolecules, we describe cryo-EM structure ribosomes from Encephalitozoon cuniculi , a eukaryote with one smallest genomes in nature. extreme rRNA reduction E. is accompanied unparalleled structural changes, such as previously unknown molten linkers bulgeless...
Abstract Ribosomal genes are widely used as ‘molecular clocks’ to infer evolutionary relationships between species. However, their utility thermometers’ for estimating optimal growth temperature of microorganisms remains uncertain. Previously, some estimations were made using the nucleotide composition ribosomal RNA (rRNA), but universal application this approach was hindered by numerous outliers. In study, we aimed address problem identifying additional indicators thermal adaptation within...
Ribosomes from different species can markedly differ in their composition by including dozens of ribosomal proteins that are unique to specific lineages but absent others. However, it remains unknown how ribosomes acquire new throughout evolution. Here, help answer this question, we describe the evolution protein msL1/msL2 was recently found parasitic microorganism clade, microsporidia. We show has a conserved location ribosome entirely dissimilar structures organisms: each analyzed species,...
ABSTRACT Currently, we are witnessing an explosive accumulation of genomic sequences for organisms across all branches life. However, typically the data lack information about optimal growth conditions corresponding organisms. As a result, it becomes challenging to use studying adaptations and biological molecules diverse environments. To address this problem, have created database Gosha, available at http://melnikovlab.com/gshc . This brings together temperatures 25,324 species, including...
ABSTRACT Drugs that target eukaryotic ribosomes are becoming increasingly important as research tools and potential therapies against cancer, fungi other pathogenic eukaryotes. However, in the absence of comparative studies, we currently do not know how many eukaryotes possess ribosomal drug-binding sites identical to those humans, significantly differ from humans. Currently, this gap knowledge is exacerbated by presence pseudogenes genomes, making these analyses challenging due our...
Drugs that target bacterial ribosomes are widely used in modern medicine and veterinary practice to treat infections prevent the spread of antimicrobial resistance. However, most studies on targeting with drugs limited just a few model organisms. Consequently, we do not know whether ribosomal drug-binding sites observed bacteria as highly conserved across is currently implied. In this study, address question using simple but powerful computational pipeline filters out rare variants...
Objective To determine the incidence, causes and neurodevelopmental impact of severe microcephaly (head circumference <–3SD) up to age 2 years. Design Binational active paediatric surveillance study undertaken in 2017–2018 identify characterise new diagnoses microcephaly. Setting UK Ireland. Participants Infants aged under 12 months at diagnosis. Interventions Observational study. Main outcome measures Incidence, aetiology outcomes Results Fifty-nine infants met case definition, whom 30...
The evolution of microbial parasites involves the interplay two opposing forces. On one hand, pressure to survive drives improve through Darwinian natural selection. other, frequent genetic drifts result in genome decay, an evolutionary process which ever-increasing burden deleterious mutations leads gene loss and gradual reduction. Here, seeking understand how this occurs at scale individual macromolecules, we describe cryo-EM analyses ribosomes from Encephalitozoon cuniculi, a eukaryote...
A bstract Ribosomal genes are widely used as “molecular clocks” to infer the evolutionary relatedness of species. It is unclear, however, whether these can also serve thermometers” precisely estimate an organism’s optimal growth temperature. Previously, some estimations were made using average nucleotide content in ribosomal RNA, but universal application this approach was prevented by numerous outliers. Here, seeking bypass problem, we asked contain additional markers thermal adaptations,...
ABSTRACT Ribosomes from different species can markedly differ in their composition by including dozens of ribosomal proteins that are unique to specific lineages but absent others. However, it remains unknown how ribosomes acquire and specialize new throughout evolution. Here, help answer this question, we describe the evolution protein msL1/msL2 was recently found parasitic microorganism clade, microsporidia. We first show has a conserved location ribosome entirely dissimilar structures...
During starvation and stress, virtually all organisms arrest protein synthesis to conserve energy. Inactive ribosomes are converted into a dormant state, in which they protected from damage by hibernation factor proteins. In bacteria, two major families of factors have been described, but the low conservation these proteins huge diversity species, habitats, environmental stressors has confounded their discovery. this study, using proteomics cryo-EM, we identify new dormancy psychrophilic...