Biology subjects

Jones, T. M.

Publications and source records attributed to Jones, T. M..

7 recordsLinked to original sources

bioRxiv2026

Capturing the rhythm: methodological choices shape inference from circadian activity data

Abstract 1. Statistical tools and analytical decisions for analysing animal activity data are often limited and poorly justified, particularly with respect to model choice, sampling design and temporal aggregation. These shortcomings can constrain our ability to draw accurate and biologically meaningful inferences about behaviour. 2. We interrogated 24 h activity data taken from individual males and females derived from five Drosophila melanogaster populations to generate a general framework for collecting and analysing activity data that systematically compares common model classes, continuous verses fragmented sampling strategies, and alternative temporal aggregation choices (time-bin sizes). 3. Our analyses identified generalised additive mixed models (GAMMs) applied to high-frequency continuous data with small-moderate bin sizes (1-5 minutes) as providing the most robust and interpretable inference for our complex, high-frequency activity data. 4. However, our interrogation of the data set confirmed that analytical and sampling decisions need to be tailored to the study species, the timing of activities and the nature of the behaviour of interest. Accordingly, polynomial and cosinor generalised linear models, increased but biologically targeted snapshot sampling, and bin sizes smaller than one hour yielded adequate analyses with similar biological conclusions when appropriately matched to the system. 5. Our approach provides an accessible decision-making framework for activity analyses that allows researchers across behavioural, ecological and evolutionary studies to justify and optimise choices about data collection and modelling. Such an approach improves the biological relevance of inference and supporting the use of modern tracking and analytical technologies.

animal behavior and cognition↗

bioRxiv2025

Conserved but mechanistically diverse piRNA defence against gypsy LTR retrotransposons in insect ovaries

Organisms have evolved highly adaptable defence systems to silence mobile genetic elements such as transposons. While individual transposons may emerge and vanish over time, the long-term evolutionary stability of the pathways that suppress them remains poorly understood. In the ovarian somatic cells of Drosophila, envelope-carrying gypsy long terminal repeat (LTR) retrotransposons are silenced by the Piwi-interacting RNA (piRNA) pathway, which depends exclusively on Piwi - an evolutionary derivative of an Aubergine/Piwi gene duplication unique to flies. Recent studies, however, have revealed that envelope-carrying gypsy elements are widespread across metazoans and particularly abundant in insect genomes, raising questions about the origin of ovarian somatic piRNA defence. Here we demonstrate that Aedes and Anopheles mosquitoes, as well as stingless bees and crickets, all produce piRNAs targeting gypsy elements in ovarian somatic cells, indicating a continuous arms race in this cellular niche for more than 400 million years of insect evolution. Notably, in Aedes aegypti, ovarian somatic cells express the same piRNA clusters as other somatic tissues, where they are known to target RNA viruses - suggesting a shared origin of anti-viral and anti-retrotransposon defences. Furthermore, we reveal striking lineage-specific differences in ovarian somatic piRNA biogenesis: slicing-independent phasing dominates in dipterans, ping-pong amplification in bees, and slicing-dependent phasing in crickets. Together, these findings indicate that distinct piRNA pathways have independently evolved at different timepoints to silence the same class of retrotransposons in insect evolution.

evolutionary biology↗

bioRxiv2025

Cis-regulatory divergence and mate recognition in behaviourally isolated cricket species.

Cis-regulatory evolution has been implicated in morphological and physiological reproductive isolation, but its role in divergence of mate recognition behaviours is unknown. The latter are often the first, most powerful mating barriers to evolve during speciation, but understanding their genetics is hampered by the context-dependence of mate choice. We circumvented this challenge by using allele-specific expression analyses in F1 hybrids of sexually isolated cricket species, Teleogryllus oceanicus and T. commodus. Female crickets choose mating partners based on species-specific male advertisement songs, and we found extensive cis-regulatory divergence in neural tissues exposed to conspecific, heterospecific, or mixed-species songs. Genes with divergent expression were implicated in learning, memory and transcriptional regulation, and they showed elevated population genetic differentiation in allopatry but not sympatry. This implies that genes recruited during evolutionary divergence of mate recognition systems may be homogenised by gene flow. Regulatory divergence was asymmetrical between the two species; divergent selection on genes associated with female perception of male song was more prominent in T. oceanicus than in T. commodus. Evolved differences in gene regulation are strongly associated with sexual signal perception in closely related species, supporting the idea that rapid cis-regulatory evolution of mate recognition can accelerate speciation.

evolutionary biology↗

bioRxiv2023

An oncogenic isoform of septin 9 promotes the formation of juxtanuclear invadopodia by reducing nuclear deformability

Invadopodia are extracellular matrix (ECM) degrading structures, which promote cancer cell invasion. The nucleus is increasingly viewed as a mechanosensory organelle that determines migratory strategies. However, how the nucleus crosstalks with invadopodia is little known. Here, we report that the oncogenic septin 9 isoform 1 (SEPT9_i1) is a component of breast cancer invadopodia. SEPT9_i1 depletion diminishes invadopodia formation and the clustering of invadopodia precursor components TKS5 and cortactin. This phenotype is characterized by deformed nuclei, and nuclear envelopes with folds and grooves. We show that SEPT9_i1 localizes to the nuclear envelope and juxtanuclear invadopodia. Moreover, exogenous lamin A rescues nuclear morphology and juxtanuclear TKS5 clusters. Importantly, SEPT9_i1 is required for the amplification of juxtanuclear invadopodia, which is induced by the epidermal growth factor. We posit that nuclei of low deformability favor the formation of juxtanuclear invadopodia in a SEPT9_i1-dependent manner, which functions as a tunable mechanism for overcoming ECM impenetrability. HighlightsO_LIThe oncogenic SEPT9_i1 is enriched in breast cancer invadopodia in 2D and 3D ECM C_LIO_LISEPT9_i1 promotes invadopodia precursor clustering and invadopodia elongation C_LIO_LISEPT9_i1 localizes to the nuclear envelope and reduces nuclear deformability C_LIO_LISEPT9_i1 is required for EGF-induced amplification of juxtanuclear invadopodia C_LI eTOC BlurbInvadopodia promote the invasion of metastatic cancers. The nucleus is a mechanosensory organelle that determines migratory strategies, but how it crosstalks with invadopodia is unknown. Okletey et al show that the oncogenic isoform SEPT9_i1 promotes nuclear envelope stability and the formation of invadopodia at juxtanuclear areas of the plasma membrane.

cell biology↗

bioRxiv2023

Cross-Protection Induced by Highly Conserved Human B, CD4+, and CD8+ T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern

BackgroundThe Coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of SARS-CoV-2 infections has decreased significantly; the long-term outlook of COVID-19 remains a serious cause of high death worldwide; with the mortality rate still surpassing even the worst mortality rates recorded for the influenza viruses. The continuous emergence of SARS-CoV-2 variants of concern (VOCs), including multiple heavily mutated Omicron sub-variants, have prolonged the COVID-19 pandemic and outlines the urgent need for a next-generation vaccine that will protect from multiple SARS-CoV-2 VOCs. MethodsIn the present study, we designed a multi-epitope-based Coronavirus vaccine that incorporated B, CD4+, and CD8+ T cell epitopes conserved among all known SARS-CoV-2 VOCs and selectively recognized by CD8+ and CD4+ T-cells from asymptomatic COVID-19 patients irrespective of VOC infection. The safety, immunogenicity, and cross-protective immunity of this pan-Coronavirus vaccine were studied against six VOCs using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model. ResultsThe Pan-Coronavirus vaccine: (i) is safe; (ii) induces high frequencies of lung-resident functional CD8+ and CD4+ TEM and TRM cells; and (iii) provides robust protection against virus replication and COVID-19-related lung pathology and death caused by six SARS-CoV-2 VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma or P1 (B.1.1.28.1), Delta (lineage B.1.617.2) and Omicron (B.1.1.529). Conclusions: A multi-epitope pan-Coronavirus vaccine bearing conserved human B and T cell epitopes from structural and non-structural SARS-CoV-2 antigens induced cross-protective immunity that cleared the virus, and reduced COVID-19-related lung pathology and death caused by multiple SARS-CoV-2 VOCs.

immunology↗

bioRxiv2022

High Frequencies of PD-1+TIM3+TIGIT+CTLA4+ Functionally Exhausted SARS-CoV-2-Specific CD4+ and CD8+ T Cells Associated with Severe Disease in Critically ill COVID-19 Patients

SARS-CoV-2-specific memory T cells that cross-react with common cold coronaviruses (CCCs) are present in both healthy donors and COVID-19 patients. However, whether these cross-reactive T cells play a role in COVID-19 pathogenesis versus protection remain to be fully elucidated. In this study, we characterized cross-reactive SARS-CoV-2-specific CD4+ and CD8+ T cells, targeting genome-wide conserved epitopes in a cohort of 147 non-vaccinated COVID-19 patients, divided into six groups based on the degrees of disease severity. We compared the frequency, phenotype, and function of these SARS-CoV-2-specific CD4+ and CD8+ T cells between severely ill and asymptomatic COVID-19 patients and correlated this with -CCCs and {beta}-CCCs co-infection status. Compared with asymptomatic COVID-19 patients, the severely ill COVID-19 patients and patients with fatal outcomes: (i) Presented a broad leukocytosis and a broad CD4+ and CD8+ T cell lymphopenia; (ii) Developed low frequencies of functional IFN-{gamma}-producing CD134+CD138+CD4+ and CD134+CD138+CD8+ T cells directed toward conserved epitopes from structural, non-structural and regulatory SARS-CoV-2 proteins; (iii) Displayed high frequencies of SARS-CoV-2-specific functionally exhausted PD-1+TIM3+TIGIT+CTLA4+CD4+ and PD-1+TIM3+TIGIT+CTLA4+CD8+ T cells; and (iv) Displayed similar frequencies of co-infections with {beta}-CCCs strains but significantly fewer co-infections with -CCCs strains. Interestingly, the cross-reactive SARS-CoV-2 epitopes that recalled the strongest CD4+ and CD8+ T cell responses in unexposed healthy donors (HD) were the most strongly associated with better disease outcome seen in asymptomatic COVID-19 patients. Our results demonstrate that, the critically ill COVID-19 patients displayed fewer co-infection with -CCCs strain, presented broad T cell lymphopenia and higher frequencies of cross-reactive exhausted SARS-CoV-2-specific CD4+ and CD8+ T cells. In contrast, the asymptomatic COVID-19 patients, appeared to present more co-infections with -CCCs strains, associated with higher frequencies of functional cross-reactive SARS-CoV-2-specific CD4+ and CD8+ T cells. These findings support the development of broadly protective, T-cell-based, multi-antigen universal pan-Coronavirus vaccines. KEY POINTSO_LIA broad lymphopenia and lower frequencies of SARS-CoV-2-specific CD4+ and CD8+ T-cells were associated with severe disease onset in COVID-19 patients. C_LIO_LIHigh frequencies of phenotypically and functionally exhausted SARS-CoV-2-specific CD4+ and CD8+ T cells, co-expressing multiple exhaustion markers, and targeting multiple structural, non-structural, and regulatory SARS-CoV-2 protein antigens, were detected in severely ill COVID-19 patients. C_LIO_LICompared to severely ill COVID-19 patients and to patients with fatal outcomes, the (non-vaccinated) asymptomatic COVID-19 patients presented more functional cross-reactive CD4+ and CD8+ T cells targeting conserved epitopes from structural, non-structural, and regulatory SARS-CoV-2 protein antigens. C_LIO_LIThe cross-reactive SARS-CoV-2 epitopes that recalled the strongest CD4+ and CD8+ T cell responses in unexposed healthy donors (HD) were the most strongly associated with better disease outcomes seen in asymptomatic COVID-19 patients. C_LIO_LICompared to severely ill COVID-19 patients and to patients with fatal outcomes, the (non-vaccinated) asymptomatic COVID-19 patients presented higher rates of co-infection with the -CCCs strains. C_LIO_LICompared to patients with mild or asymptomatic COVID-19, severely ill symptomatic patients and patients with fatal outcomes had more exhausted SARS-CoV-2-speccific CD4+ and CD8+ T cells that preferentially target cross-reactive epitopes that share high identity and similarity with the {beta}-CCCs strains. C_LI

immunology↗

bioRxiv2021

Cytoplasmic pressure maintains epithelial integrity and inhibits cell motility

Cytoplasmic pressure, a function of actomyosin contractility and water flow, can regulate cellular morphology and dynamics. In mesenchymal cells, cytoplasmic pressure powers cell protrusion through physiological three-dimensional extracellular matrices. However, the role of intracellular pressure in epithelial cells is relatively unclear. Here we find that high cytoplasmic pressure is necessary to maintain barrier function, one of the hallmarks of epithelial homeostasis. Further, our data show that decreased cytoplasmic pressure facilitates lamellipodia formation during the epithelial to mesenchymal transition (EMT). Critically, activation of the actin nucleating protein Arp2/3 is required for the reduction in cytoplasmic pressure and lamellipodia formation in response to treatment with hepatocyte growth factor (HGF) to induce EMT. Thus, elevated cytoplasmic pressure functions to maintain epithelial tissue integrity, while reduced cytoplasmic pressure triggers lamellipodia formation and motility during HGF-dependent EMT.

cell biology↗