Biology subjects

Collier, S.

Publications and source records attributed to Collier, S..

7 recordsLinked to original sources

bioRxiv2026

Temporal expression of liver-stage malaria antigens shapes vaccine efficacy

Vaccine-induced cytotoxic T cells can prevent malaria by killing parasite-infected hepatocytes during the liver stage. While several antigenic targets have been identified, little consideration has been given to their temporal expression. Here, we identified SERA1 of Plasmodium berghei as a late liver-stage target in rodent malaria and further showed that the classic vaccine antigen thrombospondin-related adhesion protein (TRAP) is only an early target. While vaccination with either antigen alone was modestly protective, combining these antigens enabled killing over the entire liver-stage, greatly improving efficacy. Given the relatively long liver-stage in human malaria, our findings imply TRAP-dependent vaccines likely utilize only a small proportion of the available liver-stage to eradicate parasites. Our findings further indicate that considerations of temporal coverage when selecting vaccine antigens will improve efficacy. One-Sentence SummaryTemporally defining presentation of liver-stage antigens informs rational combinations that maximize malaria vaccine efficacy.

immunology↗

bioRxiv2025

Buying time - increasing yield potential in wheat by extending stem elongation duration

Extending the duration of the stem elongation (SE) phase between terminal spikelet (TS) and anthesis has often been proposed as an avenue to increase wheat yield. However, accurate determination of TS is labour intensive, and existing evidence is often based on a limited number of genotypes observed under controlled conditions. Here, a Buster x Charger population comprising 108 doubled haploid lines was grown across four year-sites under UK field conditions. TS was recorded through meristem dissection and SE duration was measured as the time between TS and ear emergence (EE). Mixed model analysis across year-sites revealed high heritabilities (H2yield = 0.66, H2TS = 0.93, H2SE = 0.89, H2EE = 0.95) and strong genetic correlations between yield and the phenology traits SE and EE (rg = 0.56 and rg = 0.6, respectively). While SE duration was mainly driven by EE, independent QTL for TS suggest that SE could be modified without affecting EE. The positive effect of SE duration on yield was attributed to increased grain number per area as well as increased grain weight, through independent QTL. Although validation in broader genetic backgrounds is needed, these QTL may offer opportunities for further yield increase in a physiological breeding framework. HighlightsO_LILonger stem elongation duration increases grain number. C_LIO_LILonger stem elongation duration increases grain weight. C_LIO_LIIndependent QTL suggest the timing of stem elongation as well as its effect on yield components may be independently selectable. C_LI

genetics↗

bioRxiv2024

Post-Critical Period Transcriptional and Physiological Adaptations of Thalamocortical Connections after Sensory Loss

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/624130v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@100f64aorg.highwire.dtl.DTLVardef@29907corg.highwire.dtl.DTLVardef@cccd63org.highwire.dtl.DTLVardef@1c02318_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG Unilateral whisker denervation activates plasticity mechanisms and circuit adaptations in adults. Single nucleus RNA sequencing and multiplex fluorescence in situ hybridization revealed differentially expressed genes related to altered glutamate receptor distributions and synaptogenesis in thalamocortical (TC) recipient layer 4 (L4) neurons of the sensory cortex, specifically those receiving input from the intact whiskers after whisker denervation. Electrophysiology detected increased spontaneous excitatory events at L4 neurons, confirming an increase in synaptic connections. Elevated expression levels of Gria2 mRNA and functional GluA2 subunit of AMPA receptors at the TC synapse indicate the presence of stabilized and potentiated TC synapses to L4 excitatory neurons along the intact pathway after unilateral whisker denervation. These adaptations likely underlie the increased cortical activity observed in rodents during intact whisker sensation after unilateral whisker denervation. Our findings provide new insights into the mechanisms by which the adult brain supports recovery after unilateral sensory loss.

neuroscience↗

bioRxiv2023

Harnessing Landrace Diversity Empowers Wheat Breeding for Climate Resilience

Breeding crops resilient to climate change is urgently needed to help ensure food security. A key challenge is to harness genetic diversity to optimise adaptation, yield, stress resilience and nutrition. We examined the genetic and phenotypic diversity of the A.E. Watkins landrace collection of bread wheat (Triticum aestivum), a major global cereal, through whole-genome re-sequencing (827 Watkins landraces and 208 modern cultivars) and in-depth field evaluation spanning a decade. We discovered that modern cultivars are derived from just two of the seven ancestral groups of wheat, leaving five groups as previously untapped sources for breeding. This provides access to landrace-specific functional variations using structured germplasm, genotyping and informatics resources. Employing complementary genetic populations and approaches, we identified thousands of high-resolution quantitative trait loci (QTL) and significant marker-trait associations for major traits, revealing many Watkins-unique loci that can confer superior traits in modern wheat. Furthermore, we identified and functionally verified causative genes for climate-change adaptation, nutritional enhancement and resistance to wheat blast. Finally, we assessed the phenotypic effects of 44,338 Watkins-unique haplotypes, introgressed from 143 prioritised QTL in the context of modern cultivars, bridging the gap between landrace diversity and current breeding. This study establishes a framework for systematically utilising genetic diversity in crop improvement to achieve sustainable food security.

plant biology↗

bioRxiv2022

Developing Wolbachia-based disease interventions for an extreme environment

Aedes aegypti mosquitoes carrying self-spreading, virus-blocking Wolbachia bacteria are being deployed to suppress dengue transmission. However, there are challenges in applying this technology in extreme environments. We introduced two Wolbachia strains into Ae. aegypti from Saudi Arabia for a release program in the hot coastal city of Jeddah. Wolbachia reduced infection and dissemination of dengue virus (DENV2) in Saudi Arabian mosquitoes and showed complete maternal transmission and cytoplasmic incompatibility. Wolbachia reduced mosquito heat tolerance and egg viability, with the Wolbachia strains showing differential thermal stability. Wolbachia effects were similar across mosquito genetic backgrounds but we found evidence of local adaptation, with Saudi Arabian mosquitoes having lower egg viability but higher adult desiccation tolerance than Australian mosquitoes. Genetic background effects will influence Wolbachia invasion dynamics, reinforcing the need to use local genotypes for mosquito release programs, particularly in extreme environments like Jeddah. Our comprehensive characterization of Wolbachia strains provides a foundation for Wolbachia-based disease interventions in harsh climates.

evolutionary biology↗

bioRxiv2019

A Curvature-Enhanced Random Walker Segmentation Method For Detailed Capture of 3D Cell Surface Membranes

High-resolution 3D microscopy is a fast advancing field and requires new techniques in image analysis to handle these new datasets. In this work, we focus on detailed 3D segmentation of Dictyostelium cells undergoing macropinocytosis captured on an iSPIM microscope. We propose a novel random walker-based method with a curvature-based enhancement term, with the aim of capturing fine protrusions, such as filopodia and deep invaginations, such as macropinocytotic cups, on the cell surface. We tested our method on both real and synthetic 3D image volumes, demonstrating that the inclusion of the curvature enhancement term can improve the segmentation of the aforementioned features. We show that our method performs better than other state of the art segmentation methods in 3D images of Dictyostelium cells, and performs competitively against CNN-based methods in challenge datasets, demonstrating the ability to obtain accurate segmentations without the requirement of large training datasets. We also present an automated seeding method for microscopy data, which, combined with the curvature-enhanced random walker method, enables the segmentation of large time series with minimal input from the experimenter.

bioinformatics↗

bioRxiv2017

QuimP - Analyzing transmembrane signalling in highly deformable cells

SummaryTransmembrane signalling plays important physiological roles, with G protein-coupled cell surface receptors being particularly important therapeutic targets. Fluorescent proteins are widely used to study signalling, but the analysis of image time series can be challenging, in particular when changes in cell shape are involved. To this end we have developed QuimP software. QuimP semi-automatically tracks cell outlines, quantifies spatio-temporal patterns of fluorescence at the cell membrane, and tracks local shape deformations. QuimP is particularly useful for studying cell motility, for example in immune or cancer cells.\n\nAvailability and ImplementationQuimP (http://warwick.ac.uk/quimp) consists of a set of Java plugins for Fiji/ImageJ (http://fiji.sc/) and can be easily installed through the Fiji Updater (http://warwick.ac.uk/quimp/wiki-pages/installation). It is compatible with Mac, Windows and Unix-based operating systems, requiring version >1.45 of Fiji/ImageJ and Java 8. QuimP is released as open source (https://github.com/CellDynamics/QuimP/) under an academic licence.\n\nContactT.Bretschneider@warwick.ac.uk\n\nSupplementary InformationSupplementary materials (SI-A to SI-D) are available at Bioinformatics online. Test data is available from http://warwick.ac.uk/quimp/test_data.

bioinformatics↗