Biology subjects

Hood, E.

Publications and source records attributed to Hood, E..

4 recordsLinked to original sources

bioRxiv2025

Targeted and random mutagenesis of cassava brown streak disease susceptibility factors reveal molecular determinants of disease severity

Cassava brown streak disease (CBSD) is caused by cassava brown streak viruses (CBSVs) from the family Potyviridae. Potyvirid viral genome-linked protein (VPg) recruitment of host eukaryotic translation initiation factor 4E (eIF4E) proteins is a critical step in the viral life cycle. CBSV VPg interacts with all five cassava eIF4E-family members. Simultaneously knocking out eIF4E-family genes nCBP-1 and nCBP-2, in cultivar 60444, strongly reduces CBSD root symptoms and viral titer but does not result in complete resistance, likely due to gene family redundancy. To test for redundancy, we generated single and double mutants for each clade of the eIF4E gene family in farmer preferred cultivar TME419. Double mutants for the eIF(iso)4E and nCBP clades both exhibited reduced symptom severity, with ncbp-1 ncbp-2 having the strongest phenotype. A yeast two-hybrid screen for nCBP-2 mutants that lose VPg affinity identified fifty-one mutants, including an L51F mutant. This finding is consistent with one of the recovered cassava mutants that had a 6 amino acid deletion, including L51, in nCBP-2 and showed a reduction in symptoms relative to wild type. The data presented here suggest that generating mutations corresponding to L51F of nCBP-2 in multiple or all five cassava eIF4E proteins may lead to stronger resistance to CBSD while avoiding pleiotropic effects.

plant biology↗

bioRxiv2024

A percolation-type criticality threshold controls immune protein coating of surfaces

When a material enters the body, it is immediately attacked by hundreds of proteins, organized into complex networks of binding interactions and reactions. How do such complex systems interact with a material, "deciding" whether to attack? We focus on the "complement" system of [~]40 blood proteins that bind microbes, nanoparticles, and medical devices, initiating inflammation. We show a sharp threshold for complement activation upon varying a fundamental material parameter, the surface density of potential complement attachment points. This sharp threshold manifests at scales spanning single nanoparticles to macroscale pathologies, shown here for diverse engineered and living materials. Computational models show these behaviors arise from a minimal subnetwork of complement, manifesting percolation-type critical transitions in the complement response. This criticality switch explains the "decision" of a complex signaling network to interact with a material, and elucidates the evolution and engineering of materials interacting with the body.

biophysics↗

bioRxiv2024

Marginated neutrophils in the lungs effectively compete for nanoparticles targeted to the endothelium, serving as a part of the reticuloendothelial system

Nanomedicine has long pursued the goal of targeted delivery to specific organs and cell types but has not achieved this goal with the vast majority of targets. One rare example of success in this pursuit has been the 25+ years of studies targeting the lung endothelium using nanoparticles conjugated to antibodies against endothelial surface molecules. However, here we show that such "endothelial-targeted" nanocarriers also effectively target the lungs numerous marginated neutrophils, which reside in the pulmonary capillaries and patrol for pathogens. We show that marginated neutrophils uptake of many of these "endothelial-targeted" nanocarriers is on par with endothelial uptake. This generalizes across diverse nanomaterials and targeting moieties and was even found with physicochemical lung tropism (i.e., without targeting moieties). Further, we observed this in ex vivo human lungs and in vivo healthy mice, with an increase in marginated neutrophil uptake of nanoparticles caused by local or distant inflammation. These findings have implications for nanomedicine development for lung diseases. These data also suggest that marginated neutrophils, especially in the lungs, should be considered a major part of the reticuloendothelial system (RES), with a special role in clearing nanoparticles that adhere to the lumenal surfaces of blood vessels. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/597904v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@17e0518org.highwire.dtl.DTLVardef@809eb6org.highwire.dtl.DTLVardef@33d9a7org.highwire.dtl.DTLVardef@169863_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

Sox21b underlies the rapid diversification of a novel male genital structure between Drosophila species

The emergence and subsequent diversification of morphological novelties is a major feature of animal evolution1-9. However, in most cases little is known about the molecular basis of the evolution of novel structures and the genetic mechanisms underlying their diversification. The epandrial posterior lobes of the male genital arch is a novelty of some species of the Drosophila melanogaster subgroup10-13. The posterior lobes grasp the ovipositor of the female and then integrate between her abdominal tergites, and therefore these structures are important for copulation and species-recognition10-12,14-17. The posterior lobes evolved from co-option of a Hox regulated gene network from the posterior spiracles10 and have since diversified in shape and size in the D. simulans clade in particular over the last 240,000 years driven by sexual selection18-21. The genetic basis of this diversification is highly polygenic but to the best of our knowledge none of the causative genes have yet been identified despite extensive mapping22-30. Identifying the genes underlying the diversification of these secondary sexual structures is essential to understanding the basis of changes in their morphology and the evolutionary impact on copulation and species recognition. Here, we show that the transcription factor encoded by Sox21b negatively regulates posterior lobe size during development. This is consistent with higher and expanded expression of Sox21b in D. mauritiana, which develops smaller posterior lobes compared to D. simulans. We tested this by generating reciprocal hemizygotes and confirmed that changes in Sox21b underlie posterior lobe evolution between these two species. Furthermore, we found that differences in posterior lobe size caused by the species-specific allele of Sox21b significantly affect the duration of copulation. Taken together, our study reveals the genetic basis for the sexual selection driven diversification of a novel morphological structure and its functional impact on copulatory behaviour. HighlightsO_LISox21b regulates the development of the epandrial posterior lobes, a recently evolved novel structure of some species of the Drosophila melanogaster subgroup, which has subsequently rapidly diversified in size and shape. C_LIO_LID. mauritiana has smaller posterior lobes than D. simulans and more expansive expression of Sox21b in the developing genitalia. Using a reciprocal hemizygosity test, we show that variation in Sox21b underlies the diversification of epandrial posterior lobe size and shape between D. simulans and D. mauritiana. C_LIO_LIBehavioural tests show that the species allele of Sox21b causes differences in the duration of copulation in otherwise genetically identical backgrounds. C_LIO_LISox21b has evolved between D. simulans and D. mauritiana, and contributed to the divergence of a morphological novelty and copulatory behaviour between these two species. C_LI

evolutionary biology↗