Biology subjects

Powell, A.

Publications and source records attributed to Powell, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Breedbase 2.0 - expanding the functionality for traditional breeding and transgenics

Breedbase ( is a comprehensive, web-based, open-source breeding management and analysis software for plant breeding that was introduced to address gaps with existing software for plant breeding data. Breedbase is continually improved and developed, with new features being added as required by the breeding community. Since its inception, the capabilities of Breedbase were improved to better serve the diverse data modeling needs of additional crops beyond our original ensemble of cassava, banana, yam, sweet potato, tomato, rice, and wheat. We describe here major updates that have been made in the past 4 years, including (1) improved handling of repetitive measurements; (2) a redesigned experimental treatments interface; (3) a more fine-grained user permission system; (4) improved trial quality control workflows; (5) intercropping support; (6) the addition of a decision meeting feature that helps decision makers make the best selection with the available data; (7) transgenics and tracking tools and finally, (8) an improved field layout tool which consolidates several trials in one field. These new features integrate seamlessly with the previous feature set of Breedbase - making it one of the most feature rich breeding management softwares available.

bioinformatics↗

bioRxiv2026

Genomics and CT imaging reveal diversity in silk genes and gland morphology of webspinners

Webspinners (Insecta: Embioptera) are an unusual insect order that are known for their subsocial behavior and prolific silk-production. Due to their unique foreleg silk glands, and spider-like ability to produce silk throughout their entire life cycle, webspinners are hypothesized to have evolved silk independently from other arthropod lineages. To date, there are no reference-quality genomes available for the order, preventing the study of their silk gene origination and diversification. Here, we assembled PacBio HiFi reference genomes and characterized the silk genes present in two webspinner species, Aposthonia ceylonica and Oligotoma nigra. The genomes reveal multiple full-length copies of the primary Embioptera silk gene, e-fibroin, that have undergone both ancestral and recent gene duplications within the group. For both species, all e-fibroin paralogs show the presence of complex repeat units consisting of multiple exons and introns that are remarkably homogenized across each gene. We also used CT-scanning of the internal silk glands to provide details concerning the localization of silk production in foreleg tarsi, and interspecific morphology. Article summaryThis study introduces the first high-quality genomes for webspinners, enabling new research on silk for evolutionary biologists and materials scientists alike. The authors sequenced two embiopteran species, Aposthonia ceylonica and Oligotoma nigra, to compare silk genes and gland structure using micro-computed tomography, an imaging method that shows internal anatomy in detail. They found multiple copies of the primary silk gene in both species that likely arose from multiple duplication events at different evolutionary times. These silk genes exhibit unusual gene structure with hierarchically organized repeat units that are highly homogenized within a gene. The findings show that silk genes have a complex evolutionary history in webspinners and provide a foundation for studying silk diversity within the order, and in the broader context of insect silk.

evolutionary biology↗

bioRxiv2026

Phenotype-first covalent fragment screening identifies a synthetic lethal TYMS inhibitor in ATRX-deficient cells

Chemoproteomic mapping of covalent fragment libraries is expanding the ligandable human proteome with direct evidence of cellular target engagement. However, understanding the functional consequences of specific covalent modifications typically requires extensive downstream biological characterisation. Here we present a phenotype-first approach that integrates covalent fragment screening with chemoproteomics and genetic deconvolution in a disease-relevant context. Using isogenic ATRX wild-type and knockout eHAP iCAS9 cells, we screened a library of around 500 cysteine-reactive fragments for differential cell killing and identified a chloroacetamide fragment, PP12, that selectively impairs the viability of ATRX-deficient cells. By combining competitive click-chemoproteomics with genome-wide CRISPR synthetic lethal datasets, we identified thymidylate synthase (TYMS) as a phenotypically relevant target of PP12. Target validation was supported by crystallography, competition with the active-site inhibitor 5-fluorouracil, and impaired dTMP synthesis in cells. Mechanistically, TYMS inhibition induces replication stress that is selectively cytotoxic to ATRX-deficient cells and is dependent on FAM111A and SLFN11. This work establishes a generalisable workflow linking covalent fragment phenotypes to target deconvolution using chemoproteomics and mechanistic validation.

cell biology↗

bioRxiv2025

Genetic and developmental constraints drive parallelism in flower evolution

Evolution repeatedly gives rise to similar phenotypes, suggesting that constraints and biases make some evolutionary trajectories more likely than others, yet the mechanisms underlying this predictability remain poorly understood. Using repeated transitions to self-fertilization in a model Brassicaceae genus, we show that independent reductions in petal size arise from dosage changes at the same pleiotropic growth regulator, JAGGED (JAG). Petal development exhibits particularly high sensitivity to JAG dosage, resulting in organ-specific morphological shifts with minimal effects on other organs and limited pleiotropy. In both selfing species, these changes were drawn from functionally divergent variants whose polymorphism patterns are consistent with long-term maintenance under weak selection. Our results demonstrate how developmental network architecture and the maintenance of functional variation at pleiotropic loci combine to channel evolution toward predictable outcomes.

evolutionary biology↗

bioRxiv2025

Age- and estrous-dependent effects of psilocybin in rats

Psilocybin, a psychedelic compound in "magic" mushrooms, has promise as a novel treatment for psychiatric disorders, many of which are more prevalent in females and have onsets during adolescence. However, there is a lack of research about how factors such as sex and age affect responses to psilocybin, as well as potential safety concerns with developmental exposure. The primary objectives of this preclinical study were to determine if psilocybin-induced head twitch responses differ between adolescent and adult rats, and if estrous phase contributes to variation in female head twitch responses. Secondarily, this study sought to determine if treatment with psilocybin during adolescence has long-term effects on anxiety-associated behaviors and behavioral flexibility. Results showed that 1 mg/kg intraoral psilocybin failed to elicit head twitch responses in adolescents (P35 and P45) but elicited robust responses in adult rats. Further, adolescent psilocybin exposure did not cause long-term differences in performance on the elevated zero maze or probabilistic reversal learning tasks. Lastly, adult females in diestrus showed increased head twitch responses after 1 mg/kg psilocybin compared to females in proestrus. Head twitch responses are thought to be mediated by 5-HT2A receptors, but no age-or estrous-related differences in 5-HT2A receptor expression were observed in the medial prefrontal cortex. Collectively, these results highlight the existence of age-and sex-dependent differences in the effects of psychedelics, while finding no long-term effects on selected behaviors after adolescent exposure. These findings have implications on psychedelic study design, emphasizing the need for inclusive research considering age, sex, and hormonal status.

pharmacology and toxicology↗

bioRxiv2024

A simple method for computationally unstructuring proteins: some findings

A methodology for computationally unstructuring proteins is described and the results of its application to a variety of proteins analyzed and discussed. Some proteins prove more susceptible than others, and fold topology plays a part in this. Alpha helical structure is found to be generally somewhat robust, and, perhaps unsurprisingly, unstructuring often begins at exposed chain termini. Phosphofructokinase-1 and phosphofructokinase-2, which have similar sizes but different fold topologies, are found to differ markedly in their unstructuring behaviour.

biophysics↗

bioRxiv2024

Spherical Phenotype Clustering

Phenotypic screening experiments produce many microscope images of cells under diverse perturbations, with biologically significant responses often subtle or difficult to identify visually. A central challenge is to extract image representations that distinguish activity from controls and group phenotypically similar perturbations. In this work we propose new adaptations of contrastive loss functions that incorporate experimental metadata as learned class vectors, and a geometrically inspired variant, called SPC, where class vectors are confined to the unit sphere and updated only by attractive terms (allowing more overlap of phenotypically similar classes). The approach is tested on two popular benchmarking datasets, BBBC021 and RxRx3-core; and we also evaluate performance on uncurated screens of HaCaT cells to gauge effectiveness in a realistic use-case scenario. We find we outperform prior methods across the three datasets and on a wide array of metrics measuring phenotype grouping, biological recall, drug-target interaction and mechanism-of-action inference. We also show we maintain this improved performance compared to models over 10x larger in parameter count, and that SPC can be used as an effective fine-tuning technique. The method is easy to implement and is well suited to settings with limited data or compute resources.

bioinformatics↗

bioRxiv2024

Evolution and inhibition of the FIKK effector kinase family in P. falciparum

Among the [~]200 Plasmodium species that infect vertebrates, six infect humans. Of these, P. falciparum causes >95% of all [~]500,000 annual fatalities. Phylogenetically, P. falciparum belongs to the Laverania subgenus, a group of Plasmodium species that infect great apes. Common to Laverania species is the family of FIKK kinases. One million years ago, a single FIKK kinase conserved in all Plasmodium species gained an export element in the Laverania subgenus and expanded into the family of [~]20 atypical FIKK kinases, most of which are exported into the host cell. The fikk genes are conserved in syntenic loci across the Laverania, arguing for a rapid expansion controlling important functions in host cell remodelling and pathogenesis. We provide evidence that the FIKK paralogues evolved specific and mutually exclusive phosphorylation motif preferences, conserved across their Laverania orthologues, in a short evolutionary timeframe. Surprisingly, we find that FIKK13 has evolved exclusive tyrosine-phosphorylation preference, which was thought to be absent in Plasmodium species. Combining a crystal structure with AlphaFold2 predictions, we identify residues that determine kinase-specificity within the FIKK family in a fast-evolving flexible loop. Finally, we show that all expressed members of the FIKK kinase family can be chemically inhibited in vitro using a single compound. Such a pan-specific inhibitor of this kinase family important for virulence could reduce the ability of the parasite to gain escape-mutations and resistance.

microbiology↗

bioRxiv2023

Evolution of Opsin Genes in Caddisflies (Insecta: Trichoptera)

Insects have evolved complex and diverse visual systems in which light-sensing protein molecules called opsins couple with a chromophore to form photopigments. Insect photopigments group into three major gene families based on wavelength sensitivity: long wavelength (LW), short wavelength (SW), and ultraviolet wavelength (UV). Here, we identified 123 opsin sequences from whole genome assemblies across 25 caddisfly species (Insecta: Trichoptera). We discovered the LW opsins have the most diversity across species and form two separate clades in the opsin gene tree. Conversely, we observed a loss of the SW opsin in half of the trichopteran species in this study, which might be associated with the fact that caddisflies are active during low-light conditions. Lastly, we found a single copy of the UV opsin in all the species in this study, with one exception: Athripsodes cinereus has two copies of the UV opsin and resides within a clade of caddisflies with colorful wing patterns. SignificanceWhile opsin evolution in some insect groups has been well-characterized, it has never been studied across caddisflies. Our findings provide insight into the diversity of opsins in caddisflies and form a basis for further research into the evolutionary drivers and complex visual systems in Trichoptera.

genomics↗

bioRxiv2023

Evolution and spread of a persistent P. aeruginosa outbreak clone over decades in a single US hospital.

Whole-genome sequencing is revolutionizing bacterial outbreak investigation but its application to the clinic remains limited. In 2020, prospective and retrospective surveillance detected a Pseudomonas aeruginosa outbreak with 253 isolates collected from 82 patients in 26 wards of a hospital. Its origin was dated to the late 90s, just after the facility opened, and patient-to-patient and environment-to-patient cases of transmission were inferred. Over time, two epidemic subclones evolved in separate hosts and hospital areas, including newly opened wards, and hospital-wide sampling confirmed reservoirs persisted in the plumbing. Pathoadaptive mutations in genes associated with virulence, cell wall biogenesis, and antibiotic resistance were identified. While the latter correlated with the acquisition of phenotypic resistances to 1st (cephalosporin), 2nd (carbapenems) and 3rd (colistin) lines of treatment, maximum parsimony suggested that a truncation in a lipopolysaccharide component coincided with the emergence of a subclone prevalent in long-term infections. Since initial identification, extensive infection control efforts guided by routine, near real-time surveillance have proved successful at slowing transmission.

microbiology↗

bioRxiv2023

Serum from pregnant donors induces human beta cell proliferation and insulin secretion

Pancreatic beta cells are among the slowest replicating cells in the human body. Human beta cells usually do not increase in number with exceptions being during the neonatal period, in cases of obesity, and during pregnancy. This project explored maternal serum for stimulatory potential on human beta cell proliferation and insulin output. Gravid, full-term women who were scheduled to undergo cesarean delivery were recruited for this study. A human beta cell line was cultured in media supplemented with serum from pregnant and non-pregnant donors and assessed for differences in proliferation and insulin secretion. A subset of pregnant donor sera induced significant increases in beta cell proliferation and insulin secretion. Pooled serum from pregnant donors also increased proliferation in primary human beta cells but not primary human hepatocytes indicating a cell-type specific effect. This study suggests stimulatory factors in human serum during pregnancy could provide a novel approach for human beta cell expansion.

cell biology↗

bioRxiv2023

A chemoproteomic platform for reactive fragment profiling against the deubiquitinases

Chemoproteomics is a powerful method capable of detecting interactions between small molecules and the proteome, however its use as a high-throughput screening method for chemical libraries has so far been limited. To address this need, we have further developed a chemoproteomics workflow to screen cysteine reactive covalent fragments in cell lysates against the deubiquitinating (DUB) enzymes using activity-based protein profiling. By using targeted ubiquitin probes, we have addressed sensitivity and affinity limitations, enabling target identification and covalent fragment library profiling in a 96-well plate format. The use of data independent acquisition (DIA) methods for MS analysis combined with automated Evosep liquid chromatography (LC) reduced instrument runtimes to 21 minutes per sample and simplified the workflow. In this proof-of-concept study, we have profiled 138 covalent fragments against 57 DUB proteins and validated four hit fragments against OTUD7B and UCHL3 through site identification experiments and orthogonal biochemical activity assays. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/526632v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@2e036borg.highwire.dtl.DTLVardef@e27962org.highwire.dtl.DTLVardef@8f1caaorg.highwire.dtl.DTLVardef@1a3159a_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2022

Uncovering hidden genetic diversity: allelic resolution of insect and spider silk genes

Arthropod silk is vital to the evolutionary success of hundreds of thousands of species. The primary proteins in silks are often encoded by long, repetitive gene sequences. Until recently, sequencing and assembling these complex gene sequences has proven intractable given their repetitive structure. Here, using high-quality long-read sequencing, we show that there is extensive variation--both in terms of length and repeat motif order--between alleles of silk genes within individual arthropods. Further, this variation exists across two deep, independent origins of silk which diverged more than 500 million years ago--(1) the insect clade containing caddisflies and butterflies and (2) spiders. This remarkable convergence in previously overlooked patterns of allelic variation across multiple origins of silk suggests mechanisms for the generation and maintenance of structural protein-coding genes. Future genomic efforts to connect genotypes to phenotypes should account for such allelic variation.

genomics↗

bioRxiv2022

Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease

SARS-CoV-2 is the causative agent of COVID-19. The highly conserved viral NSP15 endoribonuclease, NendoU, is a key enzyme involved in viral immune evasion, and a promising target for the development of new classes of antivirals. Yet, the broad variety of recognition sequences, complex assembly and kinetics, and lack of structural complexes hampers the development of new competitive or allosteric inhibitors for this target. Here, we performed enzymatic characterization of NendoU in its monomeric and hexameric form, showing that hexamers are allosteric enzymes with a positive cooperative index of 2. By using cryo-EM at distinct pHs combined with X-ray crystallography and structural analysis, we demonstrate the potential for NendoU to shift between open and closed states, and assembly in larger supramolecular entities, which might serve as a mechanism of self-regulation. Further, we report results from a large fragment screening campaign against NendoU, revealing multiple new allosteric sites for the development of inhibitors.

biochemistry↗

bioRxiv2022

Structural diversity of silk heavy-chain fibroins across major caddisfly (Trichoptera) clades

BackgroundLarvae of Trichoptera produce silk to build various underwater structures allowing them to exploit a wide range of aquatic environments. The heavy chain fibroin (h-fibroin) gene encodes the primary protein component of their silk. Studies on this long (>20 kbp) and highly repetitive gene have been limited by difficulties in its sequence assembly. Recently, high-quality long-read sequencing techniques have been successfully applied to obtain the full-length h-fibroin sequence. ResultsWe used three new and five previously published genomes to identify eight full-length h-fibroin gene and protein sequences of h-fibroin across the order Trichoptera covering various endpoints of the diversity of ecological silk use in caddisflies. We analyze these together with four existing high-quality h-fibroin sequences. Across the order, we observed conserved patterns in h-fibroin (high similarity of amino(n)-/carboxyl(c)-termini, presence of characteristic repeating structural modules). However, the sequence, number, and arrangement of these repeating modules varied across clades with increasing structural complexity of h-fibroin in fixed retreat and tube-case builders compared to cocoon-builders. We also found a higher percentage of proline in fixed-retreat makers. ConclusionThis study provides characterizations of the primary structure of h-fibroin from a diverse set of caddisflies. The interplay of conserved termini and basic motif structure with high variation in repeating modules as well as the variation in the percentage of proline might be linked to differences in mechanical properties (i.e., tensile strength, toughness) related to the different silk usage. This sets a starting point for future studies to screen and correlate amino acid motifs and other sequence features with quantifiable silk properties.

genomics↗

bioRxiv2022

Primary Omicron infection elicits weak antibody response but robust cellularimmunity in children

Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We determined immune responses following Omicron BA.1/2 infection in children aged 6-14 years and related this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicited a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicited increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primed for robust antibody responses following Omicron infection but these remained primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses were robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.

immunology↗

bioRxiv2022

Long-read HiFi Sequencing Correctly Assembles Repetitive heavy fibroin Silk Genes in New Moth and Caddisfly Genomes

Insect silk is an incredibly versatile biomaterial. Lepidoptera and their sister lineage, Trichoptera, display some of the most diverse uses of silk with varying strength, adhesive qualities and elastic properties. It is well known that silk fibroin genes are long (> 20 kb) and have many repetitive motifs. These features make these genes challenging to sequence. Most research thus far has focused on conserved N- and C-terminal regions of fibroin genes because a full comparison of repetitive regions across taxa has not been possible. Using the PacBio Sequel II system and SMRT sequencing, we generated high fidelity (HiFi) long-read genomic and transcriptomic sequences for the Indianmeal moth (Plodia interpunctella) and genomic sequences for the caddisfly, Eubasilissa regina. Both genomes were highly contiguous (N50 = 9.7 Mbp/32.4 Mbp, L50 = 13/11) and complete (BUSCO Complete = 99.3%/95.2%), with complete and contiguous recovery of silk heavy fibroin gene sequences. This study demonstrates that HiFi long-read sequencing can significantly help our understanding of genes with highly contiguous, repetitive regions.

genomics↗

bioRxiv2022

Repetitive elements in the era of biodiversity genomics: insights from 600+ insect genomes

Repetitive elements (REs) are integral to the composition, structure, and function of eukaryotic genomes, yet remain understudied in most taxonomic groups. We investigated REs across 601 insect species and report wide variation in REs dynamics across groups. Analysis of associations between REs and protein-coding genes revealed dynamic evolution at the interface between REs and coding regions across insects, including notably elevated RE-gene associations in lineages with abundant long interspersed nuclear elements (LINEs). We leveraged this large, empirical data set to quantify impacts of long-read technology on RE detection and investigate fundamental challenges to RE annotation in diverse groups. In long-read assemblies we detected [~]36% more REs than short-read assemblies, with long terminal repeats (LTRs) showing 162% increased detection, while DNA transposons and LINEs showed less respective technology-related bias. In most insect lineages, 25-85% of repetitive sequences were "unclassified" following automated annotation, compared to only [~]13% in Drosophila species. Although the diversity of available insect genomes has rapidly expanded, we show the rate of community contributions to RE databases has not kept pace, preventing efficient annotation and high-resolution study of REs in most groups. We highlight the tremendous opportunity and need for the biodiversity genomics field to embrace REs and suggest collective steps for making progress towards this goal.

genomics↗