Biology subjects

Reed, J.

Publications and source records attributed to Reed, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Co-administration of simvastatin mitigates clozapine-induced lifespan extension and mitochondrial functional recovery in Drosophila melanogaster.

Antipsychotics and statins can be co-prescribed to combat the increased risk of high blood cholesterol with antipsychotic use. However, statins have been shown to interfere with mitochondrial functioning through reduced coenzyme Q expression, and second-generation antipsychotic, clozapine, has also demonstrated induced mitochondrial respiratory deficits in cell models. Despite this convergence, the combined effect of statins and antipsychotics on mitochondrial function, and mechanisms of overall health, remain poorly understood. Here we exploited the cholesterol auxotrophy of Drosophila melanogaster to investigate the effects of clozapine, simvastatin and their combination on lifespan and mitochondrial bioenergetics independently of cholesterol biosynthesis. Clozapine alone significantly extended median survival, an effect attenuated by simvastatin co-treatment. High resolution respirometry showed signs of clozapine-induced mitochondrial differences diminished with age, but this adaptation was also attenuated by simvastatin co-treatment. Using a spin probe (TEMPOL) with nitrogen-vacancy diamond quantum sensing, we directly measured free radical production and found that clozapine and simvastatin significantly increased free radical generation relative to the untreated control in early life stages. We also observed preliminary evidence of sex-specific differences in treatment response. Together, these findings suggest that clozapine induces an age-related mitochondrial adaptive response that is associated with extended lifespan and mitigated by simvastatin treatment.

physiology↗

bioRxiv2026

Antennal Lobe Dynamics And The Generation Of Diverse Response Patterns To Mechanosensory Stimulation

Sensory integration within antennal lobe (AL) is thought to play a role in the guidance of odor tracking, though while responses to olfactory input within the AL have been well-studied, responses to mechanosensory stimuli, in the form of wind speed, have received less scrutiny. Recent experimental work has systematically characterized mechanosensory responses of individual neurons within the AL, showing four distinct response patterns, labeled as sustained, transient, biphasic, and offset types; furthermore, these experiments have demonstrated that the distribution of response patterns, as well as the response type of a fixed neuron, can vary with stimulus intensity (wind speed). In this work, we develop a realistic biophysical model of the AL and, using this model, we show that internal AL dynamics are capable of generating the response patterns observed experimentally - namely, we find that response type is determined by the interplay of slow synaptic inhibition, an intrinsic calcium dependent potassium (SK) current, and stimulus strength, and hence that a heterogeneous distribution of slow inhibition and SK current strength across the AL can lead to the emergence of all four types at a fixed wind speed. Moreover, similar to experiment, we find that the distribution of response patterns across the AL changes with wind speed. Finally, we examine the distribution of response types in the presence of a simulated odor stimulus as well as odor separation by the AL in the presence versus absence of a strong mechanosensory signal.

neuroscience↗

bioRxiv2026

Directed Evolution in Codon Space

Directed evolution is commonly used in protein engineering, where mature molecules are routinely improved through iterative local search of amino acid space. Here, we extend this principle to coding DNA. We developed a language-model-guided framework that iteratively refined industry-optimized coding sequences of clinical-stage therapeutics through synonymous exploration of codon space. Across 23 antibody-based therapeutics, SynCodonLM-guided refinement significantly increased recombinant expression in CHO cells for 17 molecules (74% responder rate), without significant compromise of product-quality or biophysical attributes. Moreover, changes in model likelihood predicted expression gains more effectively than heuristic statistical or mRNA-structure descriptors, despite no explicit expression objective. Codon-level likelihood also tracked temporal progression in influenza A H1N1 sequences, indicating the model captures evolutionary signal. These results show that even production-optimized sequences retain accessible fitness in synonymous codon space, establishing directed evolution as a practical strategy to improve biologic expression, a key manufacturing bottleneck, without altering protein sequence.

bioengineering↗

bioRxiv2026

Oxaliplatin Induces Spontaneous Firing at Sensory Endings Across Touch and Proprioceptive Afferents

Spontaneous activity in primary sensory neurons has been implicated in neuropathic symptoms, yet its earliest origins and immediate functional consequences remain incompletely understood. This gap is especially consequential in chemotherapy-induced peripheral neuropathy (CIPN), where sensory toxicities commonly limit effective cancer treatment. Using in vivo recordings in rats, we show that a single dose of oxaliplatin (OX) induces spontaneous firing within 24 h across touch and proprioceptive low-threshold mechanoreceptor (LTMR) afferents. Spontaneous firing consistently originated distally in peripheral axons and was accompanied by enhanced responses to mechanical stimulation, identifying LTMR sensory endings as the earliest source of spontaneous firing and a common site for spontaneous and stimulus-evoked hyperexcitability. OX also induced early structural abnormalities at sensory endings; however, SF+ LTMRs retained mechanosensory response profiles, indicating that spontaneous firing can emerge within otherwise functional sensory endings. Although coincident spontaneous and stimulus-evoked activity distorted encoding in individual LTMRs, these effects had little impact on population LTMR responses or motor behavior relying on mechanosensory feedback. Together, these findings identify sensory endings as an early target of OX neurotoxicity and demonstrate that spontaneous firing spanning multiple tactile and proprioceptive LTMR submodalities can coexist with largely preserved sensory function, indicating that even broad engagement across mechanosensory pathways is insufficient to disrupt all LTMR-dependent functions. These observations indicate that abnormal afferent activity initiated at sensory endings may be sufficient to engage sensory pathways underlying some paresthetic symptoms while leaving others largely unaffected, whereas progression to chronic neuropathic symptoms may require subsequent recruitment of the dorsal root ganglion. HighlightsO_LIOxaliplatin rapidly induces spontaneous firing across touch and proprioceptors. C_LIO_LIThe earliest spontaneous firing localizes to sensory endings, not the DRG. C_LIO_LISensory endings are a shared site of spontaneous and evoked hyperexcitability. C_LIO_LISpontaneous firing engages some sensory pathways while sparing others. C_LI

neuroscience↗

bioRxiv2026

Context-dependent correlations mislead transcriptomic network inference in bulk and single-cell data

BackgroundCorrelation is the dominant input to co-expression module discovery and miRNA-target inference. Both rely on an implicit assumption: a Pearson coefficient pooled across heterogeneous samples, whether tissues, cancer types, or cell types, estimates one biologically meaningful quantity. Simpsons paradox makes this assumption fragile in principle, since between- group mean shifts can dominate or reverse within-group associations. How often this happens in real transcriptomic data has not been quantified. ResultsAcross 8,890 TCGA tumors from 31 cancer cohorts and 23,170,038 miRNA-mRNA pairs, 94.8% of pairs showed both positive and negative within-cohort correlations. Restricting to the high-variance domain of one million pairs, 13.3% of pooled correlations with |rglobal|[≥]0.2 reversed against the within-cohort majority at sign tolerance{varepsilon} = 0.05. Heterogeneity was the rule rather than the exception (median I2 = 0.86, IQR 0.80-0.90), and 99.5% of pairs rejected equal correlation across cohorts at FDR < 0.05. Of 692,770 experimentally validated miRTarBase v10 targets measurable in our data, only 0.9% were uniformly negative across cohorts. The pattern recurred across modalities. In GTEx, 21.0% of pooled signs disagreed with the tissue majority, and 23.5% of pairs flipped sign after tissue-mean removal. In 10x PBMC scRNA-seq, 13.1% of gene-gene correlations flipped after cell-type-mean removal; in CITE-seq, 37.9% of protein-RNA pairs flipped under a joint WNN partition of cells. Refining context reduced reversal, though by how much depended on the partition: within BRCA, 5.5% of pairs reversed under molecular PAM50 subtypes versus 0.35% under clinical IHC receptor status, and refining T cells into transcriptome-defined subtypes cut PBMC reversal from 11.8% to 0.13%. ConclusionsA single pooled correlation coefficient can invert direction relative to its within-context constituents at rates that are not negligible. Correlations should be reported with their context: the within-context distribution, a heterogeneity statistic, and a diagnostic that separates between-context mean shifts from within-context association. We provide a small R interface that computes these summaries.

bioinformatics↗

bioRxiv2026

Type IV pilus length determines virulence by regulating a hidden subpopulation of non-contributing filaments

Many clinically important bacterial pathogens, including Pseudomonas, Vibrio, Neisseria, and Acinetobacter species, employ dynamic extracellular appendages called type IV pili (T4P) to facilitate virulence through cyclical extension and retraction of pilus filaments. To dissect how T4P dynamics govern pathogenesis, we engineered a genetic system to precisely tune pilus length across a continuum. We demonstrate that pilus length critically determines four major T4P-dependent virulence traits in Pseudomonas aeruginosa (motility, surface sensing, biofilm formation, and phage infection) and reveal a hidden subpopulation of pili that are unable to interact with environmental substrates or host cells, rendering them non-contributing to any T4P-mediated function. Integrating molecular dynamics simulations, we show that low inner-membrane abundance of the major pilin forces the extension mechanism into transient idle states, restricting both velocity and final length. Molecularly, this finding reveals how two key biophysical parameters, pilin abundance and diffusion, impose a fundamental physical constraint on T4P assembly, and that regulating pilin abundance presents a strong lever over regulating pilus count for controlling the amount of functionally contributing filaments. Contrary to the prevailing view that retraction force generation primarily dictates T4P-mediated behaviors, our results establish extension dynamics as the overlooked bottleneck constraining all retraction-enabled virulence traits, with population heterogeneity in length enabling adaptive bet-hedging.

microbiology↗

bioRxiv2026

WayFindR: Investigating Feedback in Biological Pathways

Understanding biological pathways requires more than static diagrams. We present WayFindR, an R package that converts pathway data from WikiPathways and KEGG into graph structures using igraph, enabling computational analysis of regulatory features such as negative feedback loops. Rooted in control theory, negative feedback is essential for system stability, yet it is often underrepresented in curated pathway data. In this study, we systematically analyzed pathway information from both databases across multiple species and found that feedback loops--particularly negative ones--are rarely captured. This gap likely reflects both biological and technical challenges. Biologically, feedback mechanisms are inherently complex and often remain uncharted due to limited experimental focus. Technically, pathway databases frequently lack standardized annotations and complete representations of regulatory interactions, especially inhibitory edges that are crucial for identifying feedback. These observations underscore the need for improved data curation and consistent annotation practices to enhance our understanding of regulatory dynamics. By bridging the gap between static pathway diagrams and dynamic systems-level insights, WayFindR enables reproducible and scalable investigation of feedback regulation in cellular networks. The WayFindR R package can be downloaded from the Comprehensive R Archive Network (CRAN) (https://cran.r-project.org/web/packages/WayFindR/index.html). The processed data along with code for download can be accessed via the GitLab repository (https://gitlab.com/krcoombes/wayfindr).

bioinformatics↗

bioRxiv2025

Detecting Mitochondrial Free Radicals with Quantum Sensors: From Organelles to a D. melanogaster Model of Neurodegeneration

This study identifies a distinct free radical signature in a D. melanogaster model of Parkinsons Disease, successfully differentiating Pink1-deficient flies from wild-type controls. This insight was achieved using a robust quantum sensing methodology for the selective detection of free radicals in biological systems. Our approach utilizes optically detected magnetic resonance (ODMR) and magnetic modulation (MM) protocols with nanodiamond nitrogen-vacancy (NV) centres. Selective identification is achieved using the spin probe TEMPOL, a cell-permeable superoxide dismutase 2 (SOD2) mimic that initially quenches the photoluminescence signal. Upon scavenging free radicals like hydroxyl and superoxide, TEMPOL is converted to a diamagnetic adduct, restoring the contrast and thus enabling quantitative detection. The approach was first validated in a chemical system with radical generation confirmed by electron paramagnetic resonance (EPR) spectroscopy. It was then demonstrated across biological scales, from isolated mitochondria and whole glioblastoma cells to the Drosophila model. In these studies, high-resolution respirometry revealed distinct free radical signatures, and findings were compared with NV T1 relaxometry. This work provides new biophysical insight into mitochondrial dysfunction, demonstrating a distinct free radical signature in a neurodegeneration model and connecting it to specific metabolic states.

cell biology↗

bioRxiv2025

Lipid monolayers adsorbing mRNA as models for mRNA enclosed in lipid nanoparticles for transfection

In lipid-based mRNA pharmaceuticals applicable for vaccination, cancer therapy, and other types of therapeutics, the negatively charged RNA is embedded in nanoparticles containing positively charged or ionizable lipids. The local cohesion at the lipid-RNA interface plays an important role for the stability and biological activity of the resulting nanoparticles. Ions and other buffer components in the RNAs immediate surroundings may affect RNA stability against hydrolysis and its binding strength to the oppositely charged lipid layers, which is relevant for release after cellular uptake and endosomal processing. Here, we use Langmuir monolayers at the air/water interface as well-defined experimental models to study the local molecular organization of mRNA adsorbed to lipid layers. Binding of mRNA in the presence of monovalent and divalent ions from the aqueous phase to monolayers consisting of cationic transfection lipids and zwitterionic phospholipids is investigated with synchrotron-based x-ray fluorescence and scattering techniques. The experiments provide detailed insights into the structure of the adsorbed layers as well as the fractions of all molecular moieties contributing to the interfacial electrostatic balance, specifically phosphates from RNA, phosphates from phospholipids in the monolayer, and elemental counterions. The mRNA forms discrete electron-dense layers tightly bound to the lipid membrane, where cationic ions accumulate at the interface together with the mRNA. This leads to an excess of anionic nucleotides relative to cationic lipids at the interface, which is more pronounced in the presence of divalent compared to monovalent cations. The quantitative information on local interfacial moieties obtained here may constitute a valuable basis for the evaluation of quality aspects of nanoparticles comprising mRNA in the bulk phase.

biophysics↗

bioRxiv2025

Neuroligin-3 interaction with CSPG4 regulates normal and malignant glial precursors through PIEZO1

Glioma pathophysiology is robustly regulated by interactions with neurons. Key to these interactions is the role of neuroligin-3 (NLGN3), a synaptic adhesion molecule shed in response to neuronal activity1-5 that functions as a paracrine factor crucial for glioma growth. Here, we elucidate the mechanistic pathway whereby shed NLGN3 interacts with glioma and their normal glial counterpart. NLGN3 interacts with Chondroitin Sulfate Proteoglycan 4 (CSPG4) on both glioma and healthy oligodendrocyte precursor cells (OPCs)6-9, facilitating CSPG4 shedding by ADAM10. NLGN3-CSPG4 interactions and consequent shedding alter membrane tension, thereby activating PIEZO1 mechanosensitive channels and causing membrane depolarization. The NLGN3-CSPG4-PIEZO1 axis maintains OPCs in an undifferentiated, stem-like state and promotes glioma proliferation, underscoring important functional roles for the NLGN3-CSPG4-PIEZO1 axis in both healthy and malignant glial precursors.

neuroscience↗

bioRxiv2025

Invasion preferences suggest a possible role for Plasmodium falciparum parasites in the expansion of Duffy negativity in West and Central Africa

Duffy antigen receptor for chemokines (DARC) is the primary red blood cell (RBC) receptor for invasion of human RBCs by Plasmodium vivax and knowlesi parasites. By contrast, Plasmodium falciparum parasites use multiple RBC receptors for invasion. Whether DARC is one of these receptors has never been systematically explored. We used flow cytometry and microscopy-based approaches to investigate whether P. falciparum parasites preferentially invade specific Duffy RBC phenotypes and explored two potential explanations for invasion preference - differences in RBC biophysical properties and surface protein composition. P. falciparum parasites showed a consistent preference for Duffy-positive RBCs, and some biophysical properties and surface protein expression varied between Duffy-positive and Duffy-negative RBCs. We then used our in vitro invasion data to parametrise an evolutionary- epidemiological model of the relationship between P. falciparum and the FYBES allele. Our model accounts for immunity against P. falciparum virulence, gained through exposure, and thus mutations that impede infection are not always advantageous. The inhibition of P. falciparum invasion that we observed in vitro leads to FYBES frequencies increasing at low levels of P. falciparum transmission but decreasing at high levels of transmission. The impact of P. falciparum on the prevalence of Duffy negativity may therefore be most apparent in lower transmission settings. Our findings are the first to show a link between Duffy negativity and P. falciparum and suggest that DARC may direct or indirectly be involved in P. falciparum invasion of human RBCs which could, together with P. vivax, explain the distribution of Duffy negativity in sub-Saharan Africa.

evolutionary biology↗

bioRxiv2025

Benchmarking Long-read Sequencing Tools for Chromosome End-specific Telomere Analysis

Measuring chromosome end-specific telomeres is of great importance and could help elucidate better treatment algorithms and aid in a better understanding of cancer, aging, cardiovascular disease, and neurodegenerative diseases. In this study, we present a comparison of two cutting edge long-read sequencing telomere length analysis tools, TECAT and Telogator. We perform a comprehensive bench-marking of these two tools using Telseq as the standard. Our analysis included evaluating these tools on sensitivity, accuracy, and computational efficiency using a diverse data set of 9 samples from the 1000 Genomes Project which have matched long-read and short-read sequencing data. We found that while Teloga-tor demonstrated superior sensitivity, identifying on average 31% more telomeric reads across all samples, TECAT showed better accuracy with measurements more closely aligned with established literature values and Telseq benchmarks (R{superscript 2} = 0.74 vs 0.37), and TECAT displayed better computational efficiency, com-pleting tasks approximately 41% faster. Both tools successfully mapped telomere lengths to individual chromosome arms, demonstrating unprecedented resolution for telomere length analysis. Our results provide crucial insights for researchers selecting tools for telomere length analysis and highlight the current capabilities and limitations of computational approaches in telomere biology.

bioinformatics↗

bioRxiv2025

Clustering Digestive Tract Tumors Using Transcriptomic and Mutation Data

Digestive tract cancers, like most other cancers, are usually categorized based on cell or tissue of origin. Molecular clustering based on the transcriptome often produces the same classification. We developed a new method, Newmanization, to reduce underlying tissue signals from transcriptomic analysis. To test our method, we downloaded data on 1635 samples of digestive tract cancers from The Cancer Genome Atlas. The available data includes transcriptomic data, by RNA-Seq, as well as binary mutation allele frequency data by whole exome sequencing. We compared, using silhouette widths and visualization by dimension reduction plots, the effectiveness of Newmanized transcriptome and mutation data to separate digestive tract cancers. The Newmanized transcriptome clusters have clearer separation and larger average silhouette widths. Feature analysis of each cluster for Newmanized transcriptomic data and mutation data revealed that clusters determined with Newmanized data contained more mRNAs present at higher frequencies than clusters defined by mutation data. This suggests that the Newmanized method holds great potential for advancing personalized transcriptomic medicine.

bioinformatics↗

bioRxiv2024

Topological Structures in the Space of Treatment-Naive Patients With Chronic Lymphocytic Leukemia

Patients are complex and heterogeneous; clinical data sets are complicated by noise, missing data, and the presence of mixed-type data. Using such data sets requires understanding the high-dimensional "space of patients", composed of all measurements that define all relevant phenotypes. The current state-of-the-art merely defines spatial groupings of patients using cluster analyses. Our goal is to apply topological data analysis (TDA), a new unsupervised technique, to obtain a more complete understanding of patient space. We applied TDA to a space of 266 previously untreated patients with Chronic Lymphocytic Leukemia (CLL), using the "daisy" metric to compute distances between clinical records. We found clear evidence for both loops and voids in the CLL data. To interpret these structures, we developed novel computational and graphical methods. The most persistent loop and the most persistent void can be explained using three dichotomized, prognostically important factors in CLL: IGHV somatic mutation status, beta-2 microglobulin, and Rai stage. In conclusion, patient space turns out to be richer and more complex than current models suggest. TDA could become a powerful tool in a researchers arsenal for interpreting high-dimensional data by providing novel insights into biological processes and improving our understanding of clinical and biological data sets. Simple SummaryClinical data sets incorporate continuous data like blood pressure or sodium levels, categorical data like cancer grade or stage, and binary data like sex or marital status. Measurements on an individual patient define a point in a high-dimensional space; data from many patients defines a "point cloud". The "shape" of the point cloud influences experimental design by describing patient variability. Topological data analysis (TDA) is a mathematical technique for understanding the shape of point clouds by finding "holes" that correspond to combinations of patient characteristics that are never observed. TDA results are stratified by dimension. Zero-dimensional features define patient subtypes. One-dimensional features ("loops") are analogs of the inside of a circle or a donut hole. Two-dimensional features ("voids") are analogs of the inside of a balloon. Here, we apply TDA to a clinical data set of previously untreated patients with Chronic Lymphocytic Leukemia to find loops and voids.

bioinformatics↗

bioRxiv2023

Tempered IL-2 Signals Program PD-1 Checkpoint Blockade-Responsive Stem-like Exhausted T Cells During Priming

Stem-like progenitor exhausted CD8 T cells are critical for maintaining long-term resistance during chronic infections and cancer, and represent an important checkpoint blockade immunotherapy target for functional reinvigoration and disease control. Hence, there is vigorous interest in understanding the ontogenesis of TCF-1Hi stem-like exhausted CD8 T cells, and in defining the signals that promote their development. Here, we show that virus-specific TCF1HiGzmBLo CD8 T cells develop during early stages of chronic viral infection, and are progressively deprogrammed from the stem-like lineage towards terminal differentiation by strong IL-2 signals. In vivo fate-tracking studies show that strong T cell-intrinsic IL-2 signals through the high affinity heterotrimeric IL-2R/{beta}/{gamma} receptor drive skewed development of terminally differentiated TCF-1LoGzmBHi cells, which largely die in chronic antigenic environment. In contrast, tempered IL-2 signals through the intermediate affinity IL-2R{beta}/{gamma} heterodimer, or delayed priming in diminished IL-2 milieu support preferential development of TCF-1Hi stem-like exhausted CD8 T cells, capable of long-term persistence and potent responsiveness to PD-1 therapy in later stages of chronic viral infection. In human tumors as well, single cell RNA-seq analyses of tumor infiltrating lymphocytes from melanoma, human papillomavirus+ head and neck cancer and lung cancer patients revealed an inverse relationship between IL-2 signaling signature and T cell stemness. Moreover, melanoma patients with enriched IL-2 signaling signature showed poor responses to checkpoint blockade immunotherapy. Collectively, these findings bear relevance to clinical immunotherapies of chronic viral infections and cancers, and support exogenous IL-2 signal manipulation prior to therapy as a strategy for augmenting long-term clinical outcomes. ONE SENTENCE SUMMARYProgramming of exhausted T cell fates by differential IL-2

immunology↗

bioRxiv2022

The Nematode Oscheius tipulae as A Genetic Model for Programmed DNA Elimination

SUMMARYProgrammed DNA elimination (PDE) is a notable exception to the paradigm of genome integrity. In metazoa, PDE often occurs during early embryogenesis, coincident with germline to somatic cell differentiation. During PDE, portions of genomic DNA are lost, resulting in reduced somatic genomes. Recent studies have described the sequences lost and chromosome behavior in metazoa. However, a system for studying the mechanisms and consequences of PDE in metazoa is lacking. Here, we established a functional and genetic model for PDE in the free-living nematode Oscheius tipulae, a member of the Rhabditidae family, which includes Caenorhabditis elegans. O. tipulae was recently suggested to eliminate DNA. Using staged embryos, we show that O. tipulae PDE occurs during embryogenesis at the 2-16 cell stages, similar to the human/pig parasitic nematode Ascaris. We identified a conserved motif, named Sequence For Elimination (SFE), for all 12 break sites on the six chromosomes at the junction of retained and eliminated DNA. SFE mutants exhibit a "fail-to-eliminate" phenotype only at the modified sites. END-seq revealed that breaks can occur at multiple positions within the SFE, with extensive end resection followed by telomere addition to both retained and eliminated ends. We identified through END-seq in the wild-type embryos, genome sequencing of SFE mutants, and comparative genomics of 23 wild isolates a large number of functional SFEs at the chromosome ends. We suggest these alternative SFEs provide flexibility in the sequences eliminated and a fail-safe mechanism for PDE. These studies establish O. tipulae as a new, attractive model to study the mechanisms and consequences of PDE in a metazoan.

genetics↗

bioRxiv2020

Active and machine learning-based approaches to rapidly enhance microbial chemical production

In order to make renewable fuels and chemicals from microbes, new methods are required to engineer microbes more intelligently. Computational approaches, to engineer strains for enhanced chemical production typically rely on detailed mechanistic models (e.g., kinetic/stoichiometric models of metabolism) -- requiring many experimental datasets for their parameterization--while experimental methods may require screening large mutant libraries to explore the design space for the few mutants with desired behaviors. To address these limitations, we developed an active and machine learning approach (ActiveOpt) to intelligently guide experiments to arrive at an optimal phenotype with minimal measured datasets. ActiveOpt was applied to two separate case studies to evaluate its potential to increase valine yields and neurosporene productivity in Escherichia coli. In both the cases, ActiveOpt identified the best performing strain in fewer experiments than the case studies used. This work demonstrates that machine and active learning approaches have the potential to greatly facilitate metabolic engineering efforts to rapidly achieve its objectives.

systems biology↗

bioRxiv2020

Telomere length dynamics in response to DNA damage in malaria parasites

Malaria remains a major cause of morbidity and mortality within the developing world. Recent work has implicated chromosome end stability and the repair of DNA breaks through telomere healing as potent drivers of variant antigen diversification, thus associating basic mechanisms for maintaining genome integrity with aspects of host-parasite interactions. Here we applied long-read sequencing technology to precisely examine the dynamics of telomere addition and chromosome end stabilization in response to double strand breaks within subtelomeric regions. We observed that the process of telomere healing induces the initial synthesis of telomere repeats well in excess of the minimal number required for end stability. However once stabilized, these newly created telomeres appear to function normally, eventually returning to a length nearing that of intact chromosome ends. These results parallel recent observations in humans, suggesting an evolutionarily conserved mechanism for chromosome end repair.

cell biology↗