A5051754660- Genomics and Chromatin Dynamics
- Biochemical and Structural Characterization
- DNA Repair Mechanisms
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Science, Research, and Medicine
- Epigenetics and DNA Methylation
- Virus-based gene therapy research
- Biomedical and Engineering Education
- HIV Research and Treatment
- Bacterial biofilms and quorum sensing
- Advanced biosensing and bioanalysis techniques
- Antimicrobial Resistance in Staphylococcus
- Health and Medical Research Impacts
- Cytomegalovirus and herpesvirus research
- PARP inhibition in cancer therapy
- Cellular transport and secretion
- CRISPR and Genetic Engineering
- Gene Regulatory Network Analysis
- Chromosomal and Genetic Variations
- Advanced Fluorescence Microscopy Techniques
- Microbial Metabolic Engineering and Bioproduction
- Molecular Junctions and Nanostructures
- Force Microscopy Techniques and Applications
- bioluminescence and chemiluminescence research
The Francis Crick Institute
2019-2024
Biochemical Society
2018-2021
University of Cambridge
2013-2016
MRC Laboratory of Molecular Biology
2011-2012
University of York
2010-2012
Newly copied sister chromatids are tethered together by the cohesin complex, but how chromatid cohesion coordinates with DNA replication is poorly understood. Prevailing models suggest that complexes, bound to before replication, remain behind advancing fork keep together. By visualizing single forks colliding preloaded we find replisome instead pushes where a converging met. Whereas replisomes removed during termination, remains on nascent and provides cohesion. Additionally, show CMG...
The SasG surface protein of Staphylococcus aureus has been shown to promote the formation biofilm. comprises an N-terminal A domain and repeated B domains. Here we demonstrate that is involved in accumulation phase biofilm, a process requires physiological concentration Zn(2+). domains, but not domain, are required. Purified recombinant can form dimers vitro Zn(2+)-dependent fashion. Furthermore, bind cells have domains anchored their block biofilm formation. full-length exposed on cell...
Poly(ADP-ribose)polymerase-1 (PARP-1) is a highly abundant chromatin-associated enzyme present in all higher eukaryotic cell nuclei, where it plays key roles the maintenance of genomic integrity, chromatin remodeling and transcriptional control. It binds to DNA single- double-strand breaks through an N-terminal region containing two zinc fingers, F1 F2, following which its C-terminal catalytic domain becomes activated via unknown mechanism, causing formation addition polyadenosine-ribose...
Staphylococcus aureus and epidermidis form communities (called biofilms) on inserted medical devices, leading to infections that affect many millions of patients worldwide cause substantial morbidity mortality. As biofilms are resistant antibiotics, device removal is often required resolve the infection. Thus, there a need for new therapeutic strategies molecular data might assist their development. Surface proteins S. surface protein G (SasG) accumulation-associated (S. epidermidis) promote...
Homologous recombination (HR) is essential for error-free repair of DNA double-strand breaks, perturbed replication forks (RFs), and post-replicative single-stranded (ssDNA) gaps. To initiate HR, the mediator tumor suppressor protein BRCA2 facilitates nucleation RAD51 on ssDNA prior to stimulation filament growth by paralogs. Although binding has been implicated in nucleation, function double-stranded (dsDNA) remains unclear. Here, we exploit single-molecule (SM) imaging visualize...
Abstract Bacteria exploit surface proteins to adhere other bacteria, surfaces and host cells. Such need project away from the bacterial resist significant mechanical forces. SasG is a protein that forms extended fibrils on of Staphylococcus aureus promotes adherence biofilm formation. Here we show although monomeric lacking covalent cross-links, maintains highly conformation in solution. This extension mediated through obligate folding cooperativity intrinsically disordered E domains couple...
Parental histone dynamics at the replication fork are altered by free histones, leading to controlled eviction or transfer.
Many human proteins contain intrinsically disordered regions, and disorder in these can be fundamental to their function-for example, facilitating transient but specific binding, promoting allostery, or allowing efficient posttranslational modification. SasG, a multidomain protein implicated host colonization biofilm formation Staphylococcus aureus, provides another example of how play an important role. Approximately one-half the domains extracellular repetitive region SasG are unfolded...
A multimer of retroviral integrase (IN) synapses viral DNA ends within a stable intasome nucleoprotein complex for integration into host cell genome. Reconstitution the from maedi-visna virus (MVV), an ovine lentivirus, revealed large assembly containing sixteen IN subunits1. Herein, we report cryo-EM structures lentiviral prior to engagement target and following strand transfer, refined at 3.4 3.5 Å resolution, respectively. The elucidate details protein-protein protein-DNA interfaces...
Abstract The cohesin complex tethers sister chromatids together from the moment they are generated in S-phase until their separation anaphase 1,2 . This fundamental phenomenon, called chromatid cohesion, underpins orderly chromosome segregation. replisome coordinates cohesion establishment with replication of parental DNA 3 Cohesion can be established by complexes bound to before 4,5 , but how interaction pre-loaded results is not known. Prevailing models suggest passage through ring or...
SUMMARY Faithful replication of chromatin domains during cell division is fundamental to eukaryotic development. During replication, nucleosomes are disrupted ahead the fork, followed by their rapid reassembly on daughter strands from pool recycled parental and newly synthesized histones. Here, we use single-molecule imaging assays in Xenopus laevis egg extracts determine outcome fork encounters with nucleosomes. Contrary current models, majority histones evicted DNA, histone recycling,...
In 2020, the Biochemical Society conducted two surveys to assess impact of COVID-19 pandemic on researchers in molecular biosciences. Totalling over 1000 responses across both (a first-phase survey launched April 2020 and a follow-up October 2020) , feedback reflected various lockdowns restrictions implemented within UK globally.
The COVID-19 pandemic has affected scientific research across the world, emphasizing old entrenched problems as well bringing new challenges and even some opportunities. In May 2020, Biochemical Society conducted a survey of 469 researchers, all career stages, to assess impact on molecular bioscience community. results indicated that researchers early in their careers are most adversely by ongoing circumstances.
Abstract A multimer of retroviral integrase (IN) synapses viral DNA ends within a stable intasome nucleoprotein complex for integration into host cell genome. Reconstitution the from maedi-visna virus (MVV), an ovine lentivirus, revealed large assembly containing sixteen IN subunits (1). Herein, we report cryo-EM structures lentiviral prior to engagement target and following strand transfer, refined at 3.4 3.5 Å resolution, respectively. The elucidate details protein-protein protein-DNA...
The Biochemical Society held its Strategy Retreat at the end of November 2020 and, this meeting, our Council Trustees considered key opportunities and challenges in year ahead (find more on outcomes here). Following earlier commitments to represent all members community regardless career stage, it was noted that EDI (equality, diversity inclusivity) needs be as part everything we do are committed improving ‘in-house’ across committees, parallel developing strategy further. Part commitment...