Allison, L. | bioRxiv Science

bioRxiv2024

An analysis of contractile and protrusive cell behaviours at the superficial surface of the zebrafish neural plate

The motive forces underlying convergence and internalisation of the teleost neural plate remain unknown. To help understand this crucial morphogenetic movement we have analysed collective and individual cell behaviours at the superficial surface of the neural plate. Convergence to the midline does not rely on mediolateral cell intercalation, it is characterised by oscillatory contractile behaviours, a punctate distribution of Cdh2 and medially polarised actin-rich protrusions at the surface of the neural plate. Additionally, we characterise and discuss the intimate relationship and dynamic cell surfaces between the motile neural plate and the stationary overlying non-neural enveloping layer.

developmental biology↗

bioRxiv2020

Prophage-dependent recombination drives genome structural variation and phenotypic heterogeneity in Escherichia coli O157:H7

The human zoonotic pathogen Escherichia coli O157 is defined by its extensive prophage repertoire including those that encode Shiga toxin, the factor responsible for inducing life-threatening pathology in humans. As well as introducing genes that can contribute to the virulence of a strain, prophage can enable the generation of large-chromosomal rearrangements (LCRs) by homologous recombination. This work examines the types and frequencies of LCRs across the major lineages of the O157 serogroup and defines the phenotypic consequences of specific structural variants. We demonstrate that LCRs are a major source of genomic variation across all lineages of E. coli O157 and by using both optical mapping and ONT long-read sequencing demonstrate that LCRs are generated in laboratory cultures started from a single colony and particular variants are selected during animal colonisation. LCRs are biased towards the terminus region of the genome and are bounded by specific prophages that share large regions of sequence homology associated with the recombinational activity. RNA transcriptional profiling and phenotyping of specific structural variants indicated that important virulence phenotypes such as Shiga toxin production, type 3 secretion and motility are affected by LCRs. In summary, E. coli O157 has acquired multiple prophage regions over time that act as genome engineers to continually produce structural variants of the genome. This structural variation is a form of epigenetic regulation that generates sub-population phenotypic heterogeneity with important implications for bacterial adaptation and survival. Author SummaryEscherichia coli has an open genome and has acquired genetic information over evolutionary time, often in the form of bacteriophages that integrate into the bacterial genome (prophages). E. coli O157 is a clonal serogroup that is found primarily in ruminants such as cattle but can cause life-threatening infections in humans. E. coli O157 isolates contain multiple prophages including those that encode Shiga-like toxins which are responsible for the more serious disease associated with human infections. We show in this study that many of these prophages exhibit large regions of sequence similarity that allow rearrangements to occur in the genome generating structural variants. These occur routinely during bacterial culture in the laboratory and the variants are detected during animal colonization. The variants generated can give the bacteria altered phenotypes, such as increased motility or toxin production which can be selected in specific environments and therefore represent a highly dynamic mechanism to generate variation in bacterial populations without a change in overall gene content.

microbiology↗

bioRxiv2018

Universal architectural concepts underlyingprotein folding patterns

What is the architectural basis set of the observed universe of protein structures? Using information-theoretic inference, we answer this question with a comprehensive dictionary of 1,493 substructural concepts. Each concept represents a topologically-conserved assembly of helices and strands that make contact. Any protein structure can be dissected into instances of concepts from this dictionary. We dissected the world-wide protein data bank and completely inventoried all concept instances. This yields an unprecedented source of biological insights. These include: correlations between concepts and catalytic activities or binding sites, useful for rational drug design; local amino-acid sequence-structure correlations, useful for ab initio structure prediction methods; and information supporting the recognition and exploration of evolutionary relationships, useful for structural studies. An interactive site, PO_SCPLOWROCODICC_SCPLOW, at http://lcb.infotech.monash.edu.au/prosodic (click) provides access to and navigation of the entire dictionary of concepts, and all associated information.

bioinformatics↗