Biology subjects

Wills, C.

Publications and source records attributed to Wills, C..

3 recordsLinked to original sources

bioRxiv2026

Holistic meta-analysis of Caenorhabditis elegans germ granule proteomics reveals complex dynamics and new candidate granule associated proteins

Spatiotemporal organisation of biological molecules is a key driver of cellular processes, including many post-transcriptional epigenetic processes. The germline-specific germ granules are biomolecular condensates that act as hubs for mRNA and small RNA processing and are core regulators of germline gene expression programming. Germ granules have been studied extensively in C. elegans, and recent developments have led to many subdivisions of the germ granule into specialised compartments. Rapid advancements in microscopy and protein-protein interaction (PPI) screening techniques have produced a large amount of data towards characterising the localisation of proteins to specific granules. However, common methods used to probe PPIs are limited in their ability to robustly detect valid interactions, especially the multivalent and sometimes transient ones observed in granule environments. Here we perform a meta-analysis of granule protein interaction screens. While these experiments generally enrich for proteins matching the profile of granule-associated proteins, we find that when considering screens individually, reproducibility is surprisingly low, highlighting not only the variability inherent in these methods but also the dynamic nature of the PPI networks present in granules. We developed an algorithm to provide a measure of each proteins association with specific granules across various experiments. By further clustering and investigation of the resulting score matrix, we demonstrate the power of this holistic approach to provide deeper insights into germ granule organisation and highlight novel can provide a resource to better inform future investigations into granules and their constituent proteins.

genetics↗

bioRxiv2024

Genetic modifiers of somatic expansion and clinical phenotypes in Huntington's disease reveal shared and tissue-specific effects

Huntingtons disease (HD), due to expansion of a CAG repeat in HTT, is representative of a growing number of disorders involving somatically unstable short tandem repeats. We find that overlapping and distinct genetic modifiers of clinical landmarks and somatic expansion in blood DNA reveal an underlying complexity and cell-type specificity to the mismatch repair-related processes that influence disease timing. Differential capture of non-DNA-repair gene modifiers by multiple measures of cognitive and motor dysfunction argues additionally for cell-type specificity of pathogenic processes. Beyond trans modifiers, differential effects are also illustrated at HTT by a 5-UTR variant that promotes somatic expansion in blood without influencing clinical HD, while, even after correcting for uninterrupted CAG length, a synonymous sequence change at the end of the CAG repeat dramatically hastens onset of motor signs without increasing somatic expansion. Our findings are directly relevant to therapeutic suppression of somatic expansion in HD and related disorders and provide a route to define the individual neuronal cell types that contribute to different HD clinical phenotypes.

genetics↗

bioRxiv2022

Mircubactin B rescues the lethal effect of cell wall biosynthesis mutations in Bacillus subtilis.

Growth of most rod-shaped bacteria is accompanied by the insertion of new peptidoglycan into the cylindrical cell wall. This insertion, which helps maintain and determine the shape of the cell, is guided by a complex protein machinery called the rod complex or elongasome. Although most of the proteins in this complex are essential under normal growth conditions, cell viability can be rescued, for reasons that are not understood, by the presence of a high (mM) Mg2+ concentration. We screened for natural product compounds that could rescue the growth of mutants affected in rod-complex function. By screening >2,000 extracts from a diverse collection of actinobacteria, we identified a new compound, mirubactin B, related to the known iron siderophore mirubactin A, which rescued growth in the low micromolar range, and this activity was confirmed by synthesising mirubactin B. The compound also displayed toxicity at higher concentrations, and this effect appears related to iron homeostasis. However, several lines of evidence suggest that the mirubactin B rescuing activity is not due simply to iron sequestration. The results demonstrate a novel antibacterial compound and add to growing evidence that bacterial siderophores have a range of activities beyond simple iron sequestration.

microbiology↗