Biology subjects

Hunt, J.

Publications and source records attributed to Hunt, J..

9 recordsLinked to original sources

bioRxiv2026

Symbiont-mediated shifts in cuticular hydrocarbon profiles reduce female attractiveness after mating

Males can influence future mating interactions of females after copulation by changing female signals that subsequent males will encounter. In insects, such effects commonly involve cuticular hydrocarbons (CHCs), but whether heritable microbial symbionts contribute to post-mating chemical signalling remains largely unknown. Kelly's citrus thrips, Pezothrips kellyanus, provides an ideal system to address this question because reproductive compatibility is shaped by common arthropod endosymbionts. Across P. kellyanus populations, Cardinium occurs in almost all individuals whereas Wolbachia varies in prevalence and appears to spread by cytoplasmic incompatibility (CI). Yet, females with only Cardinium (C) avoid incompatible males carrying both Cardinium and Wolbachia (CW), and this discrimination is linked to the distinct CHC profile of CW males. Here, we tested whether this endosymbiont-associated male perfume persists on females beyond copulation by altering the female CHC profile and subsequent male mating behaviour. Using behavioural assays and GC-MS-based CHC profiling, we found that, independent of female endosymbiont association, females first mated with CW males received fewer antennal contacts and mating attempts from subsequent C males. Furthermore, mating remodelled female CHC profiles, while mating with CW males produced a distinctive post-mating chemical signature. Most notably, tridecane, previously detected only in CW males, occurred exclusively in females mated with CW males. Our findings show that endosymbionts can alter mated female CHCs and influence future sexual communication between male and female hosts. These findings reveal a previously unrecognised post-mating route through which endosymbionts reshape sexual communication, with potential consequences for reproductive compatibility and symbiont transmission dynamics.

evolutionary biology↗

bioRxiv2026

Combinatorial screening of biological degrader modules identifies heterobifunctional molecules that efficiently destroy MYC, leading to rapid tumour cell death in vitro and in vivo

Targeted protein degradation is a potent strategy against intracellular proteins impervious to traditional drugs. We describe a platform reliant on high-throughput cloning and mRNA-based delivery to quickly screen 100s-1000s of modular biological degraders, which we challenge against the high-turnover c-Myc oncoprotein. We uncover critical principles to drive degrader discovery against any target, free from tagging or prior cell line engineering, with direct applications in research and potentially therapy. We demonstrate the feasibility of targeted protein degradation of c-Myc across in vitro cancer models and in vivo xenograft model, uncovering distinct cellular responses between c-Myc degradation and inhibition.

bioengineering↗

bioRxiv2025

Anti-activin treatment increases T cell infiltration in breast and pancreatic tumours and promotes survival in a SMAD4-null mouse pancreatic cancer model

Activin A and B share the same downstream signalling pathway (activation of SMAD2/3) as TGF-{beta} and consequently elicit many of the same functional responses as TGF-{beta}, including immune suppression, activation of cancer-associated fibroblasts (CAFs) and extracellular matrix production and remodelling. However, activins role in tumourigenesis has been relatively overlooked compared to TGF-{beta}s. We generated and characterized a dual specificity human antibody that recognizes both activin A and B and compared its activity in syngeneic mouse models of breast cancer and pancreatic ductal adenocarcinoma (PDAC) with an activin A-specific antibody. We demonstrate that activin A and B are central to the function of CAFs and therapeutic inhibition of activin results in a reduction of collagen rich desmoplastic barriers, enabling the infiltration of cytotoxic T cells. This is correlated with an upregulation of the T cell chemoattractant CXCL10, which is normally repressed by activin signalling. Interestingly, despite greater T cell infiltration, activin A inhibition resulted in poorer survival in the KPC mouse model of PDAC and slightly larger tumours in the breast cancer model, indicating a tumour suppressive role of activin A-rich CAFs. Strikingly, however, treatment with the same anti-activin A antibody of PDAC tumours where SMAD4 is deleted in the tumour cells, resulted in increased survival, which was potentiated with additional treatment with immune checkpoint inhibitors. These results suggest that anti-activin therapy has potential for the cohort of PDAC patients exhibiting inactivation of SMAD4.

cancer biology↗

bioRxiv2025

A systemic clock brake: Period1 stabilizes the circadian network under environmental stress

Precise alignment between internal circadian clocks and environmental light cycles is essential for physiological homeostasis and survival. However, the molecular mechanisms that preserve this synchrony across central and peripheral tissues remain poorly defined. Here, we uncover an unexpected role for the core clock gene Period1 (Per1) as a systemic modulator of circadian stability, regulating light-induced re-entrainment across the brain and body. In Per1-deficient mice, we show that loss of Per1 accelerates clock realignment, influencing transcriptomic, metabolic, hormonal, and behavioral indicators of circadian realignment across multiple organ systems, including the suprachiasmatic nucleus (SCN) and peripheral tissues such as the liver, adipose tissue, and adrenal glands. Notably, this accelerated adaptation confers protection against jetlag-induced sleep disturbances, weight gain, and metabolic imbalance, underscoring a systemic role for Per1 in maintaining circadian network stability. Mechanistically, unbiased spatial transcriptomics identified reduced expression of the arginine vasopressin (AVP), a key neuropeptide mediating SCN intercellular coupling, as the driver of circadian network instability. Weakened SCN synchrony permits enhanced flexibility of peripheral oscillator responses, expediting whole-body adaptation to shifted light-dark schedules. These findings position Per1 as a critical regulator of circadian robustness, a buffer against light over-responsiveness, identifying a potential molecular target for mitigating circadian misalignment in contexts such as jetlag, shift work, and metabolic disease. TeaserWhat if beating jetlag was as simple as switching off a gene? Researchers show that disabling Per1, a core circadian regulator, accelerates body clock realignment and protects against sleep and metabolic disruption--highlighting new therapeutic possibilities for jetlag and shift work.

neuroscience↗

bioRxiv2025

High-resolution Staphylococcus profiling reveals intra-species diversity in a single skin niche

The skin microbiome is dominated by a few key genera, among which Staphylococcus is one of the most well-characterised. Recent studies have examined the roles of various Staphylococcus species such as S. epidermidis and S. hominis within broader skin microbial communities. However, these investigations often rely on isolates from multiple individuals and hence, limiting their ability to capture intra-community interactions. In this study, we focused on the axillary microbiome of a single healthy individual to characterise the genetic and functional diversity of resident Staphylococcus isolates. Using a low-cost, high-throughput DNA extraction and long-read whole genome sequencing pipeline, we generated complete genomes for 93 isolates spanning seven genetically distinct lineages across three major skin species. These comprised of one dominant with three additional lineages of S. epidermidis, two of S. hominis and one of S. capitis. Functional and metabolic analyses revealed species- and strain-specific features, suggesting potential metabolic cross-feeding and specialisation within this community, including within strains of S. epidermidis. These findings highlight the metabolic complexity and potential interdependence of staphylococci inhabiting a single skin site and the need for strain-level resolution of the community. The strains form part of the York Skin Microbiome (YSM) collection, a growing open biobank of genetically diverse skin isolates from matched individuals.

microbiology↗

bioRxiv2025

A high-quality reference genome and comparative genomics of the widely-farmed bandedcricket (Gryllodes sigillatus) identifies selective breeding targets

Farmed insects have gained attention as an alternative, sustainable source of protein with a lower carbon footprint than traditional livestock. We present a high-quality reference genome for one of the most commonly farmed insects, the banded cricket Gryllodes sigillatus. In addition to its agricultural importance, G. sigillatus is also a model in behavioural and evolutionary ecology research on reproduction and mating systems. We report comparative genomic analyses that clarify the banded crickets evolutionary history, identify gene family expansions and contractions unique to this lineage, associate these with agriculturally important traits, and identify targets for genome-assisted breeding efforts. The high-quality G. sigillatus genome assembly plus accompanying comparative genomic analyses serve as foundational resources for both applied and basic research on insect farming and behavioural biology, enabling researchers to pinpoint trait-associated genetic variants, unravel functional pathways governing those phenotypes, and accelerate selective breeding efforts to increase the efficacy of large-scale insect farming operations.

genomics↗

bioRxiv2024

Neural substrates for saccadic modulation of visual representations in mouse superior colliculus

How do sensory systems account for stimuli generated by natural behavior? We addressed this question by examining how an ethologically relevant class of saccades modulates visual representations in the mouse superior colliculus (SC), a key region for sensorimotor integration. We quantified saccadic modulation by recording SC responses to visual probes presented at stochastic saccade-probe latencies. Saccades significantly impacted population representations of the probes, with early enhancement that began prior to saccades and pronounced suppression for several hundred milliseconds following saccades, independent of units visual response properties or directional tuning. To determine the cause of saccadic modulation, we presented fictive saccades that simulated the visual experience during saccades without motor output. Some units exhibited similar modulation by fictive and real saccades, suggesting a sensory-driven origin of saccadic modulation, while others had dissimilar modulation, indicating a motor contribution. These findings advance our understanding of the neural basis of natural visual coding.

neuroscience↗

bioRxiv2019

Further Exploration of the SAR of Imidazoquinolines; Identification of Potent C7 Substituted Imidazoquinolines

Small molecule agonists of TLR7/8, such as imidazoquinolines, are validated agonists for the treatment of cancer and for use in vaccine adjuvants. Imidazoquinolines have been extensively modified to understand the structure-activity relationship (SAR) at the N1- and C2-positions resulting in the clinical drug imiquimod, resiquimod, and several other highly potent analogues. However, the SAR of the aryl ring has not been fully elucidated in the literature. This initial study examines the SAR of C7-substituted imidazoquinolines. These compounds not only demonstrated that TLR7/8 tolerate changes at the C7 position but can increase potency and change their cytokine profiles. The most notable TLR7/8 agonists developed from this study 5, 8, and 14 which are up to 4-fold and 2-fold more active than resiquimod for TLR8 and/or TLR7, respectively, and up to 100-fold more active than the FDA approved imiquimod for TLR7.

bioengineering↗

bioRxiv2018

Silent crickets reveal the genomic footprint of recent adaptive trait loss

Secondary trait loss is widespread and has profound consequences, from generating diversity to driving adaptation. Sexual trait loss is particularly common1. Its genomic impact is challenging to reconstruct because most reversals occurred in the distant evolutionary past and must be inferred indirectly2, and questions remain about the extent of disruption caused by pleiotropy, altered gene expression and loss of homeostasis3. We tested the genomic signature of recent sexual signal loss in Hawaiian field crickets, Teleogryllus oceanicus. Song loss is controlled by a sex-linked Mendelian locus, flatwing, which feminises male wings by erasing sound-producing veins. This variant spread rapidly under pressure from an eavesdropping parasitoid fly. We sequenced, assembled and annotated the T. oceanicus genome, produced a high-density linkage map, and localised flatwing on the X chromosome. We characterised pleiotropic effects of flatwing, including changes in embryonic gene expression and alteration of another sexual signal, chemical pheromones. Song loss is associated with pleiotropy, hitchhiking and genome-wide regulatory disruption which feminises flatwing male pheromones. The footprint of recent adaptive trait loss illustrates R. A. Fishers influential prediction that variants with large mutational effect sizes can invade genomes during the earliest stages of adaptation to extreme pressures, despite having severely disruptive genomic consequences.

evolutionary biology↗