- Genomics and Phylogenetic Studies
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Genomic variations and chromosomal abnormalities
- Bacterial Identification and Susceptibility Testing
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
- Microtubule and mitosis dynamics
- Plant and Fungal Interactions Research
- Chromosomal and Genetic Variations
- Malaria Research and Control
- Theatre and Performance Studies
- Bacterial biofilms and quorum sensing
- Genomics and Chromatin Dynamics
- Genetics, Bioinformatics, and Biomedical Research
- DNA Repair Mechanisms
- Infections and bacterial resistance
- Vibrio bacteria research studies
- Pharmaceutical and Antibiotic Environmental Impacts
- Clostridium difficile and Clostridium perfringens research
- Streptococcal Infections and Treatments
- Biosensors and Analytical Detection
- Helicobacter pylori-related gastroenterology studies
- vaccines and immunoinformatics approaches
- Neonatal and Maternal Infections
Wellcome Sanger Institute
2017-2024
Universidad Autónoma de La Laguna
2019
University of Cambridge
2015-2017
Addenbrooke's Hospital
2016
Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent parts Asia and Africa often associated with dominant H58 haplotype. Reduced susceptibility to fluoroquinolones also widespread, sporadic cases third-generation cephalosporins or azithromycin have been reported. Here, we report first large-scale emergence spread novel S Typhi clone harboring three first-line drugs (chloramphenicol,...
Genomic havoc from one fateful mistake Many human tumors display scrambled genomes that arise two distinct mutational processes. The first, the chromosome breakage-fusion-bridge (BFB) cycle, produces gene amplification and genomic instability. second, chromothripsis, generates massive, clustered rearrangements in or a few chromosomes. Umbreit et al. hypothesized these processes are mechanistically related tested this idea by recreating essential steps of BFB cycle cultured cells (see...
The major human bacterial pathogen
ObjectivesGenome sequencing will be increasingly used in the clinical setting to tailor antimicrobial prescribing and inform infection control outbreaks. A recent technological innovation that could reduce delay between pathogen sampling data generation is single molecule sequencing. An example of this technology, which undergoing evaluation through an early access programme, Oxford Nanopore MinION.
Malaria results in over 600,000 deaths annually, with the highest burden of young children living sub-Saharan Africa. Molecular surveillance can provide important information for malaria control policies, including detection antimalarial drug resistance. However, genome sequencing capacity malaria-endemic countries is limited. We designed and implemented an end-to-end workflow to detect Plasmodium falciparum resistance markers diversity vaccine target circumsporozoite protein (csp) using...
Dissemination of carbapenem resistance among pathogenic Gram-negative bacteria is a looming medical emergency. Efficient spread within and between bacterial species facilitated by mobile genetic elements. We hypothesized that wastewater contributes to the dissemination carbapenemase-producing Enterobacteriaceae (CPE), studied this through cross-sectional observational study in East England. isolated clinically relevant CPE untreated treated wastewater, confirming waste treatment does not...
Translating the Oxford Nanopore MinION sequencing technology into medical microbiology requires on-going analysis that keeps pace with technological improvements to instrument and release of associated software. Here, we use a multidrug-resistant Enterobacter kobei isolate as model organism compare open source software for assembly genome data, relate this time taken generate actionable information. Three tools (PBcR, Canu miniasm) were used assemble data fourth (SPAdes) was combine Illumina...
Drug-resistant bacteria are a major cause of illness worldwide, and specific subtype called Escherichia coli ST131 causes significant number these infections. become resistant to treatments by modifying their DNA transferring genes among one another via large packages plasmids, like game pass-the-parcel. Tackling infections more effectively requires better understanding what plasmids being exchanged exact contents. To achieve this, we applied new high-resolution sequencing technology six...
The frequent occurrence of disease outbreaks in humans caused by group A Streptococcus (GAS) is an on-going public health threat. Conventional bacterial typing methods lack the discriminatory power to confidently confirm or refute hospital and community settings. Microbial whole genome sequencing (WGS) provides a potential solution this, but, there has been limited population-based surveillance with accompanying sequence data. We performed retrospective genomic 93 clinical GAS isolates from...
There is growing evidence that patients with Clostridiumdifficile -associated diarrhoea often acquire their infecting strain before hospital admission. Wastewater known to be a potential source of surface water contaminated C. difficile spores. Here, we describe study used genome sequencing compare isolated from multiple wastewater treatment plants across the East England and clinical disease at major in same region. We confirmed 65 were highly diverse most cases not linked other active...
Abstract Background Important regulation occurs at the level of transcription in Plasmodium falciparum and growing evidence suggests that these apicomplexan parasites have complex regulatory networks. Recent studies implicate long noncoding RNAs (lncRNAs) as transcriptional regulators P. . However, due to limited research lack necessary experimental tools, our understanding their role malaria-causing parasite remains largely unelucidated. In this work, we address one limitations, an updated...
ABSTRACT The chromosome breakage-fusion-bridge (BFB) cycle is a mutational process that produces gene amplification and genome instability. Signatures of BFB cycles can be observed in cancer genomes with chromothripsis, another catastrophic process. Here, we explain this association by identifying cascade downstream bridge formation generates increasing amounts chromothripsis. We uncover new role for actomyosin forces breakage mutagenesis. Chromothripsis then accumulates starting aberrant...
Increasingly rich metadata are now being linked to samples that have been whole-genome sequenced. However, much of this information is ignored. This because linking genes, or regions the genome, usually relies on knowing gene sequence(s) responsible for particular trait measured and looking its presence absence in genome. Examples would be spread antimicrobial resistance genes carried mobile genetic elements (MGEs). although it possible routinely identify gene, identifying unknown MGE upon...
Copy number variants (CNVs) are genomic rearrangements implicated in numerous congenital and acquired diseases, including cancer. The appearance of culture-acquired CNVs human pluripotent stem cells (PSCs) has prompted concerns for their use regenerative medicine. A particular problem PSC is the frequent occurrence q11.21 region chromosome 20. However, exact mechanism origin this amplicon remains elusive due to difficulty delineating its sequence breakpoints. Here, we have addressed using...
Abstract Malaria is a global public health priority causing over 600,000 deaths annually, mostly young children living in Sub-Saharan Africa. Molecular surveillance can provide key information for malaria control, such as the prevalence and distribution of antimalarial drug resistance. However, genome sequencing capacity endemic countries be limited. Here, we have implemented an end-to-end workflow P. falciparum genomic Ghana using Oxford Nanopore Technologies, targeting resistance markers...
Antimicrobial resistance genes can be carried on plasmids or mobile elements integrated into the chromosome. We sequenced a multidrug resistant Enterobacter kobei genome isolated from wastewater in United Kingdom, but were unable to conclusively identify short read assembly. Our aim was compare and contrast accuracy characteristics of open source software (PBcR, Canu, miniasm SPAdes) for assembly bacterial genomes (including plasmids) generated by MinION instrument. Miniasm produced an...
Abstract The incidence of infections caused by extraintestinal Escherichia coli (ExPEC) is rising globally, which a major public health concern. ExPEC strains that are resistant to antimicrobials have been associated with excess mortality, prolonged hospital stays and higher healthcare costs. E. ST131 clonal group worldwide variable plasmid composition, has an array genes enabling antimicrobial resistance (AMR). isolates frequently encode the AMR bla CTX-M-14/15/27 , often rearranged,...
Abstract When defining bacterial populations through whole genome sequencing (WGS) the samples often have detailed associated metadata that relate to disease severity, antimicrobial resistance, or even rare biochemical traits. comparing these populations, it is apparent some of phenotypes do not follow phylogeny host i.e. they are genetically unlinked evolutionary history bacterium. One possible explanation for this phenomenon genes moving independently between hosts and likely with mobile...
Abstract Copy number variants (CNVs) are genomic rearrangements implicated in numerous congenital and acquired diseases, including cancer. In human pluripotent stem cells (PSC), the appearance of culture-acquired CNVs prompted concerns for their use regenerative medicine applications. A particularly common problem PSC is occurrence q11.21 region chromosome 20. However, exact mechanisms origin this amplicon remains elusive due to difficulty delineating its sequence breakpoints. Here, we used...
Abstract Background Important regulation occurs at the level of transcription in Plasmodium falciparum and growing evidence suggests that these apicomplexan parasites have complex regulatory networks. Recent studies implicate long noncoding RNAs (lncRNAs) as transcriptional regulators P. . However, due to limited research lack necessary experimental tools, our understanding their role malaria-causing parasite remains largely unelucidated. In this work, we address one limitations, an updated...