Biology subjects

Ellis, A.

Publications and source records attributed to Ellis, A..

13 recordsLinked to original sources

bioRxiv2025

Status of Florida's pillar coral population: in situ declines and ex situ successes

The population of the pillar coral, Dendrogyra cylindrus, in Florida was decimated from 2013-2020, primarily by the emergence of stony coral tissue loss disease (SCTLD). Monitoring of survivors from 2021 - early 2025 showed that the population underwent an additional 96% decline in live tissue, 78% loss in living colonies, and 57% loss of genotypes. SCTLD continued to be the primary cause of these losses. Though some surviving tissue isolates exhibited small amounts of growth, the population remains extremely small, with only an estimated 9.6 square meters of tissue remaining on 23 colonies (15 genotypes). Additionally, colonies are far too dispersed to successfully fertilize spawned gametes. The further declines in the population since 2020 highlight the instability of the remnant population, as well as the value of the pillar coral rescue program and ongoing propagation efforts. As of February 2025, eight different in situ and ex situ facilities were caring for rescued D. cylindrus. Experimental fragmentation at one in situ nursery identified variable, but continually increasing, growth rates across multiple fragmentation events. Sexual propagation efforts at an ex situ nursery documented 105 different rescue fragments spawning across five years. The smallest fragment was 9 x 7 x 9 cm, establishing a potential "minimum colony size" for reproductive capacity for this species. From these spawning events, 82 juveniles were being raised ex situ in early 2025. Two of these sexually propagated juveniles spawned six years after settlement, thus establishing a potential minimum age for reproduction.

ecology↗

bioRxiv2025

Pollinator and flower morphology interact to influence pollen receipt

Pollinators are important drivers of floral divergence and speciation in plants. Here we investigate the effects of floral trait variation and trait matching on pollen receipt in two different plant species, Tritoniopsis revoluta (Iridaceae) and Nerine humilis (Amaryllidaceae) each visited by long-proboscid nemestrinid flies and solitary bees across their ranges. Using single visits by pollinators to flowers in populations with experimentally increased variance in floral morphology, we demonstrate that pollinators with different morphology affect pollen receipt differently through their interactions with floral traits. This study provides details of how the mechanical fit between floral and pollinator morphology may drive floral divergence through its effects on pollen deposition, both within populations using multiple pollinators and between populations with contrasting pollinators.

evolutionary biology↗

bioRxiv2025

Exploring MicroRNA Strand Selection: Insights into Gene Regulation and Development

MicroRNAs (miRNAs) are central regulators of gene expression, yet how cells choose between the two strands (5p or 3p) of a miRNA duplex during biogenesis remains unresolved. Here, we present a comprehensive, experimentally grounded framework that decodes the logic of miRNA strand selection. Using Caenorhabditis elegans as a model system, we developed a high-throughput qPCR platform enabling precise quantification of strand usage across developmental stages and in specific somatic tissues. To uncover the molecular grammar guiding this process, we built a predictive machine learning model trained on experimentally validated strand usage data. This AI-driven model, integrating 77 biologically informed features, accurately predicts strand preference not only in nematodes but also across vertebrates, including humans, revealing compositional and structural biases that are conserved yet functionally repurposed. Our analysis shows that strand selection is not stochastic but follows conserved, context-dependent rules shaped by cellular and developmental cues. To support the research community, we provide open-access resources: a database of strand usage profiles, predictive scores across species, and code and protocols via GitHub. This work offers the first unified, generalizable model for miRNA strand selection, establishing a paradigm that combines large-scale experimentation with AI to reveal a conserved, programmable layer of gene regulation.

molecular biology↗

bioRxiv2025

Attenuation of the 2022 global outbreak monkeypox virus relative to its clade IIb ancestor

Monkeypox virus (MPXV) is a zoonotic virus endemic to Africa that has recently re-emerged, becoming the first orthopoxvirus with human-to-human transmission since smallpox eradication. The 2022 global epidemic of MPXV was caused by Clade IIb lineage B.1 virus that derives from the Clade IIb lineage A.1, which is endemic to West Africa1-3. Here we compared an early lineage B.1 virus with its closest earlier A.1 ancestor and show that despite only 46 nucleotide differences, lineage B.1 has attenuating phenotypic changes. Both B.1 and A.1 viruses replicated equivalently in cell culture, but B.1 had defects in long-range spread. MPXV B.1 also displayed defects in innate immune control, inducing higher IFN{beta}, innate immune signalling and MAPK gene expression, and a reduced capacity to suppress interleukin-1{beta}-mediated immune responses. Finally, MPXV B.1 had reduced virulence in a mouse model of MPXV infection relative to the ancestral A.1 endemic strain. Our work demonstrates biological differences between human circulating MPXV lineages that correlate with clinical observations documenting reduced in-host viral dissemination and disease severity for lineage B. Our data also reveal that the APOBEC3-like mutational footprint in MPXV is not only a signature of sustained human transmission but can also drive phenotypic changes.

microbiology↗

bioRxiv2025

Poaching exacerbates the effects of climate change on the long-term viability of an endemic South African succulent plant species

O_LINatural populations often face multiple threats that jeopardise their viability, yet most population forecasts consider only single threats, such as shifts in precipitation or temperature. To better understand ecological and conservation challenges, incorporating multiple threats is essential. South African endemic dwarf succulents, for example, are under dual threats from climate change and illegal harvesting for the ornamental plant trade. C_LIO_LIWe developed a stochastic integral projection model (IPM) using demographic data from 1999-2003, for 4776 individuals of the dwarf succulent, Argyroderma pearsonii, to evaluate the impacts of climate change and harvesting on its short-term (<40 years) extinction risk and long-term viability. We built simulations to explore 90 scenarios combining climate conditions (historical, mild climate change [SSP126], and moderate climate change [SSP245]), harvesting methods (fruit harvesting, non-selective plant harvesting, or size-selective plant harvesting), and harvest frequencies (annual to once every decade). We supplemented our approach with perturbation analyses to identify critical demographic components influencing population persistence. C_LIO_LIWe show that historically A. pearsonii populations have been stable or growing. Populations are predicted to remain viable under mild climate change, but moderate climate change results in declines in approximately 50% of simulated populations, though extinctions are not projected within 40 years without harvesting. In contrast, plant harvesting significantly increases extinction risk, especially size-selective harvesting of mature individuals, which disrupts demographic components critical to population growth. Even harvesting as infrequently as once per decade under historical climates leads to declines, with climate change exacerbating these effects. C_LIO_LISynthesis: Illegal harvesting poses a critical threat to biodiversity, as shown in this case study of a South African endemic succulent. Our findings indicate that plant harvesting is unsustainable under any scenario, particularly with projected climatic pressures. However, fruit collection emerges as a potentially sustainable alternative to meet the ornamental plant trades demands. Our study highlights the importance of incorporating multiple threats into population forecasts, providing valuable tools for ecologists and conservation managers. C_LI

ecology↗

bioRxiv2024

Transiently boosting Vγ9+Vδ2+ γδ T cells early in Mtb coinfection of SIV-infected juvenile macaques does not improve Mtb host resistance.

Children living with HIV have a higher risk of developing tuberculosis (TB), a disease caused by the bacterium Mycobacterium tuberculosis (Mtb). Gamma delta ({gamma}{delta}) T cells in the context of HIV/Mtb coinfection have been understudied in children, despite in vitro evidence suggesting {gamma}{delta} T cells assist with Mtb control. We investigated whether boosting a specific subset of {gamma}{delta} T cells, phosphoantigen-reactive V{gamma}9+V{delta}2+ cells, could improve TB outcome using a nonhuman primate model of pediatric HIV/Mtb coinfection. Juvenile Mauritian cynomolgus macaques (MCM), equivalent to 4-8-year-old children, were infected intravenously (i.v.) with SIV. After 6 months, MCM were coinfected with a low dose of Mtb and then randomized to receive zoledronate (ZOL), a drug that increases phosphoantigen levels, (n=5; i.v.) at 3- and 17-days after Mtb accompanied by recombinant human IL-2 (s.c.) for 5 days following each ZOL injection. A similarly coinfected MCM group (n=5) was injected with saline as a control. V{gamma}9+V{delta}2+ {gamma}{delta} T cell frequencies spiked in the blood, but not airways, of ZOL+IL-2-treated MCM following the first dose, however, were refractory to the second dose. At necropsy eight weeks after Mtb, ZOL+IL-2 treatment did not reduce pathology or bacterial burden. {gamma}{delta} T cell subset frequencies in granulomas did not differ between treatment groups. These data show that transiently boosting peripheral {gamma}{delta} T cells with ZOL+IL-2 soon after Mtb coinfection of SIV-infected MCM did not improve Mtb host defense.

immunology↗

bioRxiv2024

The Caenorhabditis elegans bacterial microbiome influences microsporidia infection through nutrient limitation and inhibiting parasite invasion

Microsporidia are eukaryotic obligate intracellular parasites that infect most animals including humans. To understand how the microbiome can impact microsporidia infection, we tested how bacterial isolates that naturally occur with Caenorhabditis elegans influence infection by the microsporidian Nematocida parisii. Nematodes exposed to two of these bacteria, Chryseobacterium scopthalmum and Sphingobacterium multivorum, exhibit reduced pathogen loads. Using untargeted metabolomics, we show that unsaturated fatty acid levels are disrupted by growth on these bacteria and that supplementation with the polyunsaturated fatty acid linoleic acid can restore full parasite growth in animals cultured on S. multivorum. We also found that two isolates, Pseudomonas lurida and Pseudomonas mendocina, secrete molecules that inactivate N. parisii spores. We determined that P. lurida inhibits N. parisii through the production of massetolides. We then measured 53 additional Pseudomonas strains, 64% of which significantly reduced N. parisii infection. A mixture of Pseudomonas species can greatly limit the amount of infection in C. elegans populations over many generations. Our findings suggest that interactions between bacteria and N. parisii are common and that these bacteria both modulate host metabolism and produce compounds that inhibit microsporidia infection.

microbiology↗

bioRxiv2024

Metabolomics and 13C Labelled Glucose Tracing to Identify Carbon Incorporation into Aberrant Cell Membrane Glycans in Cancer

Cell membrane glycans contribute to immune recognition, signaling, and cellular adhesion and migration, and altered membrane glycosylation is a feature of cancer cells that contributes to cancer progression. The uptake and metabolism of glucose and other nutrients essential for glycan synthesis could underlie altered membrane glycosylation, but the relationship between shifts in nutrient metabolism and the effects on glycans have not been directly examined. To address this possibility, we created a novel method that combines stable isotope tracing with metabolomics to enable direct observations of glucose allocation to nucleotide sugars and cell-membrane glycans. We compared the glucose allocation to membrane glycans of two pancreatic cancer cell lines that are genetically identical but have differing energy requirements. The 8988-S cells had higher glucose allocation to membrane glycans and intracellular pathways relating to glycan synthesis, but the 8988-T cells had higher glucose uptake and commitment of glucose to non-glycosylation pathways. The cells lines differed in requirements of glucose for energy production, resulting in differences in glucose bioavailability for glycan synthesis. The workflow demonstrated here enables studies on the effects of metabolic shifts on the commitment of media nutrients to cell-membrane glycans. The results support a flux-based regulation of glucose commitment glycosylation and a mode of metabolic control of cell functions such signaling, immune recognition, and adhesion and migration.

cancer biology↗

bioRxiv2023

Type I IFN expression is inhibited during cell division by CDK4/6

Cells are equipped to defend themselves from invading pathogens through sensors such as cGAS, which upon binding DNA induces type I interferon (IFN) expression. Whilst IFNs are crucial for limiting viral infection and activating adaptive immunity, uncontrolled production causes excessive inflammation and autoimmunity. cGAS binds DNA of both pathogenic and cellular origin and its activity is therefore tightly regulated. This is particularly apparent during mitosis, where cGAS association with chromatin following nuclear membrane dissolution and phosphorylation by mitotic kinases negatively regulate enzymatic activity. Here we describe a novel mechanism by which DNA sensing and other innate immune pathways are regulated during cell division, dependent on cyclin dependent kinases (CDK) 4 and 6. Inhibition of CDK4/6 using chemical inhibitors, shRNA-mediated depletion, or overexpression of cellular CDK4/6 inhibitor p16INK4a, greatly enhanced DNA- or cGAMP-induced expression of cytokines and IFN-stimulated genes (ISG). Mechanistically, CDK4/6-dependent inhibition mapped downstream of cytoplasmic signalling events including STING and IRF3 phosphorylation, limiting innate immune induction at the level of IFN{beta} mRNA expression. This regulation was universal, occurring in primary and transformed cells of human and murine origin, and broad, as IFN{beta} expression was inhibited in a CDK4/6-dependent manner downstream of multiple pattern recognition receptors. Together these findings demonstrate that host innate responses are limited by multiple mechanisms during cell division, thus defining cellular replication as an innate immune privileged process that may be necessary to avoid aberrant self-recognition and autoimmunity.

immunology↗

bioRxiv2022

Long read single cell RNA sequencing reveals the isoform diversity of Plasmodium vivax transcripts

Plasmodium infections often consist of heterogenous populations of parasites at different developmental stages and with distinct transcriptional profiles, which complicates gene expression analyses. The advent of single cell RNA sequencing (scRNA-seq) enabled disentangling this complexity and has provided robust and stage-specific characterization of Plasmodium gene expression. However, scRNA-seq information is typically derived from the end of each mRNA molecule (usually the 3-end) and therefore fails to capture the diversity in transcript isoforms documented in bulk RNA-seq data. Here, we describe the sequencing of scRNA-seq libraries using Pacific Biosciences (PacBio) chemistry to characterize full-length Plasmodium vivax transcripts from single cell parasites. Our results show that many P. vivax genes are transcribed into multiple isoforms, primarily through variations in untranslated region (UTR) length or splicing, and that the expression of these isoforms is often developmentally regulated. Our findings demonstrate that long read sequencing can be used to characterize mRNA molecules at the single cell level and provides an additional resource to better understand the regulation of gene expression throughout the Plasmodium life cycle. Author SummarySingle cell RNA-sequencing is a valuable tool for identifying cell specific differences in heterogenous populations. However, scRNA-seq has limitations in assigning reads to genes of organisims with poorly annotated UTRs, due to the poly-A caputre utilized by some scRNA-seq technologies, this technical limitation also makes identifying transcript specific differences, like alternative splicing, difficult. Despite its importance in human disease the P. vivax genome annotation is still relatively sparce, especially in the UTRs, and very little is known about transcript differece in the different life stages of the parasite life cycle. Here, we utilize a modified version of 10X scRNA-seq technology to capture full length transcripts via PacBio sequencing from both sporozoite and blood stages of P. vivax. This allowed us to predict full length stage specific transcripts for P. vivax as well as identify important variation in the previously poorly annotated UTRs. These findings will aide in futhering our understanding of P. vivax transcript regulation across the life cycle stages.

genomics↗

bioRxiv2020

Mathematical modeling of N-803 treatment in SIV-infected non-human primates

Immunomodulatory drugs could contribute to a functional cure for Human Immunodeficiency Virus (HIV). Interleukin-15 (IL-15) promotes expansion and activation of CD8+ T cell and natural killer (NK) cell populations. In one study, an IL-15 superagonist, N-803, suppressed Simian Immunodeficiency Virus (SIV) in non-human primates (NHPs) who had received prior SIV vaccination. However, viral suppression attenuated with continued N-803 treatment, partially returning after long treatment interruption. While there is evidence of concurrent drug tolerance, immune regulation, and viral escape, the relative contributions of these mechanisms to the observed viral dynamics have not been quantified. Here, we utilize mathematical models of N-803 treatment in SIV-infected macaques to estimate contributions of these three key mechanisms to treatment outcomes: 1) drug tolerance, 2) immune regulation, and 3) viral escape. We calibrated our model to viral and lymphocyte responses from the above-mentioned NHP study. Our models track CD8+ T cell and NK cell populations with N-803-dependent proliferation and activation, as well as viral dynamics in response to these immune cell populations. We compared mathematical models with different combinations of the three key mechanisms based on Akaike Information Criterion and important qualitative features of the NHP data. Two minimal models were capable of reproducing the observed SIV response to N-803. In both models, immune regulation strongly reduced cytotoxic cell activation to enable viral rebound. Either long-term drug tolerance or viral escape (or some combination thereof) could account for changes to viral dynamics across long breaks in N-803 treatment. Theoretical explorations with the models showed that less-frequent N-803 dosing and concurrent immune regulation blockade (e.g. PD-L1 inhibition) may improve N-803 efficacy. However, N-803 may need to be combined with other immune therapies to countermand viral escape from the CD8+ T cell response. Our mechanistic model will inform such therapy design and guide future studies. Author summaryImmune therapy may be a critical component in the functional cure for Human Immunodeficiency Virus (HIV). N-803 is an immunotherapeutic drug that activates antigen-specific CD8+ T cells of the immune system. These CD8+ T cells eliminate HIV-infected cells in order to limit the spread of infection in the body. In one study, N-803 reduced plasma viremia in macaques that were infected with Simian Immunodeficiency Virus, an analog of HIV. Here, we used mathematical models to analyze the data from this study to better understand the effects of N-803 therapy on the immune system. Our models indicated that inhibitory signals may be reversing the stimulatory effect of N-803. Results also suggested the possibilities that tolerance to N-803 could build up within the CD8+ T cells themselves and that the treatment may be selecting for virus strains that are not targeted by CD8+ T cells. Our models predict that N-803 therapy may be made more effective if the time between doses is increased or if inhibitory signals are blocked by an additional drug. Also, N-803 may need to be combined with other immune therapies to target virus that would otherwise evade CD8+ T cells.

systems biology↗

bioRxiv2020

TransMPRA: A framework for assaying the role of many trans-acting factors at many enhancers

Gene regulation occurs through trans-acting factors (e.g. transcription factors) acting on cis-regulatory elements (e.g. enhancers). Massively parallel reporter assays (MPRAs) functionally survey large numbers of cis-regulatory elements for regulatory potential, but do not identify the trans-acting factors that mediate any observed effects. Here we describe transMPRA -- a reporter assay that efficiently combines multiplex CRISPR-mediated perturbation and MPRAs to identify trans-acting factors that modulate the regulatory activity of specific enhancers.

genomics↗

bioRxiv2018

Connect-seq to superimpose molecular on anatomical neural circuit maps

The mouse brain contains ~100 million neurons interconnected in a vast array of neural circuits. The identities and functions of individual neuronal components of most circuits are undefined. Here we describe a method, termed Connect-seq, which combines retrograde viral tracing and single cell transcriptomics to uncover the molecular identities of upstream neurons in a specific circuit and the signaling molecules they use to communicate. Connect-seq can generate a molecular map that can be superimposed on a neuroanatomical map to permit molecular and genetic interrogation of how the neuronal components of a circuit control its function. Application of this method to hypothalamic neurons controlling physiological responses to fear and stress reveal subsets of upstream neurons that express diverse constellations of signaling molecules and can be distinguished by their anatomical locations.

neuroscience↗