Biology subjects

Phelps, M.

Publications and source records attributed to Phelps, M..

8 recordsLinked to original sources

bioRxiv2026

Fly, land, listen: Autonomous intermittent locomotion enables scalable low-noise drone ecoacoustic surveys

Ecoacoustic monitoring is enabling scientists and land managers to monitor and manage biodiversity more effectively and cost-efficiently in the face of human pressures and rapidly changing climates. Currently, most ecoacoustic surveys use manually deployed static sensors to record data, limiting the scale and reach of surveying efforts. Here we present a proof-of-concept autonomous drone platform that can use intermittent locomotion to conduct ecoacoustic surveys using an onboard sensor. Our custom prototype is able to fly, navigate, and avoid obstacles autonomously, land at a pre-determined location, record audio from an onboard microphone whilst static, before taking off and moving to the next sampling site. Autonomous navigation and operation enable greater sampling flexibility, reach, and scalability. Furthermore, by recording audio only whilst landed, noise from the drone's rotors does not mask signals or disturb animals, simplifying signal processing and downstream ecological analyses. We conducted trials in a scrubland habitat at the Knepp Estate in West Sussex, where our prototype demonstrated successful autonomous navigation and obstacle avoidance. Furthermore, we found that avian biodiversity data collected from the drone platform was comparable to that from traditional static acoustic sensor deployments, and that vocalisation patterns were not significantly impacted by the noise of the drone arriving or leaving a site. While scaled deployments of our technology would require further technical and regulatory challenges to be solved, our first demonstration of autonomous intermittent robotics-assisted ecoacoustic surveys lays the foundations for more cost-effective and far-reaching biodiversity surveys, with transformative potential for conservation, agricultural management, biosecurity, and more.

ecology↗

bioRxiv2026

Skeletons in the closet: The importance of actin in alphavirus replication

The ability of the bacterial endosymbiont Wolbachia pipientis to block arboviruses in its mosquito host may be impinged by host genetic variation, leading to reduced efficacy in field releases. Across a large collection of Drosophila lines carrying natural genetic variation, we found that viral replication varied greatly in the absence of Wolbachia. However, the introduction of the symbiont reduced viral load in each background to similar levels, near the limit of detection. Therefore, Wolbachia-mediated viral blocking is seemingly robust against host genetic background. A genome-wide association study harnessing the variation in the viral loads across the Wolbachia-free set identified rhoGAP18B and betaCOP as host factors that contribute to SINV replication; furthermore, the gene products of which seemingly interact with each other in the context of cytoskeletal dynamics. These results shed light on host requirements for SINV replication and suggest possible avenues by which Wolbachia may encroach upon them during blocking.

microbiology↗

bioRxiv2025

Targeted metagenomic sequencing with spiked primers for enrichment of viruses in wastewater for pathogen surveillance

BackgroundWastewater surveillance offers an underutilized opportunity to identify high-risk viral pathogens that pose public health risks. Although metagenomic approaches have been increasingly adopted for human wastewater surveillance, little attention has been given to its application in rural agricultural settings. Untargeted metagenomic sequencing of wastewater poses considerable technical challenges for viral detection due to fragmented genomes and low viral abundance. While existing enrichment methods partially address these challenges, high costs and proprietary protocols limit adoption in resource-constrained settings. ObjectiveWe developed a fully open-source primer design algorithm (Open MSSPE Design) and evaluated Metagenomic Sequencing with Spiked Primer Enrichment (MSSPE)1, as a practical strategy for metagenomic surveillance of swine slurry and farm wastewater samples collected from rural agricultural settings. This non-invasive MSSPE strategy addresses the challenge of detecting extremely low-abundance viral targets amid samples dominated by a background of bacterial and eukaryotic nucleic acids. MethodologyWe generated fifteen primer sets targeting high-priority DNA and RNA viral pathogens affecting human and animal health in Southeast Asia using our open-source primer design algorithm. Twenty-five wastewater and swine slurry samples from smallholder farms in northern Thailand underwent parallel library preparation--untargeted mNGS and MSSPE--for direct comparison. Libraries were sequenced on Illumina platforms and analyzed using Chan Zuckerberg ID (CZ ID)2. Rarefaction analysis assessed performance at sequencing depths of 100,000-1.5 million reads per sample. ResultsWe detected multiple high-risk DNA and RNA viruses in wastewater samples from smallholder farm operations. MSSPE achieved substantial viral enrichment across nine pathogenic DNA and RNA viruses, with a median two-fold enrichment of reads per million, with variability across targets (IQR: 1.01-3.44x) and a nearly 10% median increase in breadth of genome coverage (IQR: 4.54-11.84%), while retaining sensitivity for untargeted pathogens. MSSPE also increased the odds of detecting targeted viruses (OR 1.35, CI 1.14-1.60), with the greatest advantage at shallow sequencing depths where MSSPE required fewer reads to identify targeted viral taxa relative to mNGS. ConclusionsMSSPE demonstrated the ability to enrich shallow-depth sequencing (<2M reads per sample) sufficiently to detect priority viruses without substantially increasing library preparation time or cost. This open-source workflow supports cost-effective metagenomic viral surveillance for resource-constrained settings, providing a non-invasive method for detecting low-abundance viral targets in high-background sample types at rural agricultural interfaces with elevated risk of zoonotic spillover.

genomics↗

bioRxiv2025

Functional Activity of HIV-1 bNAbs Across Diverse Strains is Driven by Binding Site and Can be Enhanced Through Fc Engineering

Broadly neutralizing antibodies (bNAbs) are promising tools for HIV-1 treatment and prevention, due to their ability to mediate both Fab-dependent neutralization and Fc-dependent effector functions. While antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) have been implicated in antiviral activity, the extent to which these functions vary across bNAb epitopes, viral strains, and Fc region remains unclear. Here, we systematically evaluated twenty bNAbs targeting five distinct Env epitopes against a diverse panel of nine HIV-1 strains. We found that epitope specificity and Env sequence both critically influenced bNAb effector functions. CD4 binding site (CD4bs)- and V3 glycan-targeting bNAbs mediated the broadest and most potent ADCC and ADCP, while V1/V2 apex-directed bNAbs preferentially induced ADCP. In contrast, MPER-targeting bNAbs triggered ADCC more selectively, and gp120/gp41 interface-targeting bNAbs showed limited activity. Irrespective of binding epitope, different strains exhibited a broad range of effector function sensitivities. To investigate the impact of Fc modifications on this variability, we subclass-switched and introduced previously identified Fc mutations known to change Fc{gamma} receptor affinity. Some of these mutations significantly boosted ADCC, while IgG3 subclass switching dramatically enhanced ADCP, even against highly resistant strains. Collectively, these results demonstrate that effector function is shaped by both antibody specificity and viral Env context and that rational Fc modification has the potential to improve antibody-based therapeutics against HIV. One Sentence SummaryThis study systematically evaluates the impact of bNAb epitope specificity, Env sequence, and Fc engineering on antibody-mediated effector functions.

immunology↗

bioRxiv2025

Wolbachia uses ankyrin repeats to target specific fly proteins

Arthropods, the most diverse phylum on Earth, are hosts to a plethora of bacterial parasites that secrete various effectors of unknown function during infection. The most prevalent of these is the intracellular bacterium Wolbachia pipientis. The microbe infects between 40-60% of insect species, causes important reproductive manipulations, and limits virus replication in arthropod vectors, becoming a promising biocontrol agent. Understanding the molecular basis of Wolbachia infection and Wolbachia-induced phenotypes is critical to the use of Wolbachia in vector control. These Wolbachia ankyrin repeat proteins (WARPs) represent a highly dynamic and diverse part of the Wolbachia pangenome and remain thus far, largely uncharacterized. Here, we perform molecular and genetic screens to identify interactions between Wolbachia wMel WARPs and their target host proteins in Drosophila melanogaster. Our results identify strong interactions of two Wolbachia proteins, WARP434 and WARP754, with two host targets (CG11327 and Ptp61F, respectively). Heterologous expression of these two WARPs is extremely toxic in Drosophila tissues and the toxicity is dependent on the ankyrin repeat domain of each WARP. Importantly, knockdown of the host targets alleviates toxicity, confirming WARP/target interactions. Finally, antibodies targeting both WARPs show expression by Wolbachia during infection of Drosophila cells. Understanding how Wolbachia manipulates its host biology and which host pathways it targets during infection will help us divine how the most prevalent intracellular bacterial parasite on Earth interacts with its insect hosts at the molecular level. Our screen is the first step towards that goal. ImportanceMolecular interactions drive co-evolutionary arms races between hosts and pathogens. These interactions shape the structure and function of both host and parasite proteins, enabling immunity or virulence during infection. Understanding the molecular details that unfold during these events illustrates not only how hosts and parasites co-evolve at the molecular level but also may help characterize the function of poorly understood proteins. The most prevalent intracellular infection on earth is Wolbachia pipientis, with between 40-60% of insects harboring the bacterial symbiont. Understanding how Wolbachia infects host cells and the molecular tools it uses to alter cell biology is critical to the use of the microbe in vector control. Here, we identify Wolbachia proteins used by the symbiont to interface with specific host proteins. Understanding the molecular mechanisms underlying this host-microbe interaction will shed light on how an important symbiont, used in the control of vector populations and disease transmission, uses WARPs to interact with host targets and how targeting this host protein contributes to infection.

microbiology↗

bioRxiv2022

A Homology Guide for Pacific Salmon Genus Oncorhynchus resolves patterns of Duplicate Retention, Rediploidization and Local Adaptation Following the Salmonid Specific Whole Genome Duplication Event

Salmonid fishes have emerged as a tractable model to study whole genome duplications (WGD) as this group has undergone four rounds of WGD, with a significant proportion of the genome yet to rediploidize. The fact that much of modern salmonid genomes retain duplicates from the most recent WGD while other regions have rediploidized creates complications for genetic studies by obscuring homology relationships and the necessity of filtering duplicate regions from many analyses. The difficulty this creates is particularly prominent in Pacific salmonids genus Oncorhynchus who are the focus of intense genetics-based conservation and management efforts owing to the important ecological and cultural role these fish play. To address this gap, we generated a homology guide for six species of Oncorhynchus with available genomes and used this guide to describe patterns of duplicate retention and rediploidization. Overall, we find that retained duplicates comprise over half of modern gene repertoires and that retained duplicate genes are enriched for genes involved in nuclear stability, while rediploidized genes which represent a smaller proportion of genes are heavily enriched in dosage sensitive processes such as mitochondria. Additionally, by reanalyzing published expression data from locally adapted strains of O. mykiss we demonstrate that retained duplicates are more likely to be associated with adaptive divergence than rediploidized genes, highlighting the potential of WGDs to promote adaptation. Finally, we demonstrate the utility of our homology guide by investigating the evolutionary relationship among genes highlighted as playing a role in salmonid life history traits or gene editing targets.

genomics↗

bioRxiv2022

Antibody-mediated prevention of vaginal HIV transmission is dictated by IgG subclass in humanized mice

HIV broadly neutralizing antibodies (bNAbs) are capable of both blocking viral entry and recruiting innate immunity to HIV-infected cells through their fragment crystallizable (Fc) region. Vaccination or productive infection results in a polyclonal mixture of class-switched IgG antibodies comprised of four subclasses, each encoding distinct Fc regions that differentially engage innate immune functions. Despite evidence that innate immunity contributes to protection, the relative contribution of individual IgG subclasses is unknown. Here we use vectored immunoprophylaxis (VIP) in humanized mice to interrogate the efficacy of individual IgG subclasses during prevention of vaginal HIV transmission by VRC07, a potent CD4-binding site directed bNAb. We find that VRC07-IgG2, which lacks Fc-mediated functionality, exhibits significantly reduced protection in vivo relative to other subclasses. However, even low concentrations of highly functional VRC07-IgG1 yields substantial protection against vaginal challenge, suggesting that interventions capable of eliciting modest titers of functional subclasses may provide meaningful benefit against infection.

immunology↗

bioRxiv2019

Investigating Transfusion-Related Sepsis using Culture-Independent Metagenomic Sequencing

BackgroundTransfusion-related sepsis remains an important hospital infection control challenge. Investigating septic transfusion events is often restricted by the limitations of bacterial culture in terms of time requirements and low yield in the setting of prior antibiotic administration.\n\nMethodsIn three Gram-negative septic transfusion cases, we performed mNGS of direct clinical blood specimens in addition to standard culture-based approaches utilized for infection control investigations. Pathogen detection leveraged IDSeq, a new open-access microbial bioinformatics portal. Phylogenetic analysis was performed to assess microbial genetic relatedness and understand transmission events.\n\nResultsmNGS of direct clinical blood specimens afforded precision detection of pathogens responsible for each case of transfusion-related sepsis, and enabled discovery of a novel Acinetobacter species in a platelet product that had become contaminated despite photochemical pathogen reduction. In each case, longitudinal assessment of pathogen burden elucidated the temporal sequence of events associated with each transfusion-transmitted infection. We found that informative data could be obtained from culture-independent mNGS of residual platelet products and leftover blood specimens that were either unsuitable or unavailable for culture, or that failed to grow due to prior antibiotic administration. We additionally developed methods to enhance accuracy for detecting transfusion-associated pathogens sharing taxonomic similarity to contaminants commonly found in mNGS library preparations.\n\nConclusionsCulture-independent mNGS of blood products afforded rapid and precise assessment of pathogen identity, abundance and genetic relatedness. Together, these challenging cases demonstrated the potential for metagenomics to advance existing methods for investigating transfusion-transmitted infections.

microbiology↗