Biology subjects

Turner, M.

Publications and source records attributed to Turner, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Navigating the oligomeric landscape of the periplasmic stress response protease-chaperone DegP with charge detection mass spectrometry

DegP is a periplasmic protease-chaperone essential for protein quality control and virulence factor trafficking in Gram-negative bacteria. In its apo form, DegP adopts a dynamic ensemble of oligomers derived from trimer building blocks through two competing self-assembly pathways. Upon engaging client proteins, apo DegP oligomers redistribute into discrete cage structures inside which the clients are encapsulated. The cage ensembles formed depend on the size of the bound clients, and notably can include 12mers, 24mers, and 60mers. Previous studies mapped the DegP oligmeric landscape using dynamic light scattering, analytical ultracentrifugation, nuclear magnetic resonance spectroscopy, and electron cryomicroscopy, modalities which in general report ensemble averages and often cannot directly delineate closely related coexisting species. Here, we apply charge detection mass spectrometry (CDMS) to directly measure the masses of individual DegP ions, resolving the complete oligomeric distribution in the absence and presence of four clients of increasing size. We reveal previously undetected odd-numbered oligomers and quantify the relative abundance of each assembly. Through heat-cool cycling CDMS experiments, we track cage distribution changes and reveal client protection and refolding, providing a direct view of the chaperone capabilities of DegP. These results further establish CDMS as a powerful single-molecule tool for dissecting heterogeneous protein assembly landscapes.

biochemistry↗

bioRxiv2026

Resolving symmetry-masked allosteric cooperativity in the M. tuberculosis proteasome core particle

The 20S proteasome core particle (CP) is a stacked 7-{beta}7-{beta}7-7 assembly in which the central {beta}-rings host fourteen catalytic active sites responsible for regulated protein degradation. Allosteric coupling between catalytic {beta}-subunits has been characterized in eukaryotic proteasomes, whose heteromeric {beta}-rings permit subunit-specific perturbation. In bacterial proteasomes, however, the {beta}-rings are homomeric, and any allosteric relationships between subunits with identical sequences have remained refractory to conventional ensemble-averaging structural methods, including to hydrogen/deuterium exchange mass spectrometry (HDX-MS). Here we show that orthosteric inhibitors paradoxically activate the Mycobacterium tuberculosis 20S CP at substoichiometric concentrations, revealing positive cooperativity between its {beta}-subunits. To dissect this cooperativity within the {beta}-ring, we co-assemble wild-type and catalytically inactive (T1A) {beta}-subunits into hybrid 20S CPs. We develop a probabilistic model relating bulk mixing ratios to the ensemble of hybrid 20S CP stoichiometries. Differential 15N-labelling of the wild-type subunits then resolves WT and T1A peptide signals by mass during HDX-MS, enabling subunit-resolved measurements within a single complex. Using this approach, we demonstrate that ligand binding at one {beta}-subunit remodels the conformational dynamics of binding-incompetent neighbours. Measuring deuterium uptake against ring composition identifies two allosteric routes: a lateral pathway from switch helix II to the active site of the adjacent intra-ring subunit, and an axial pathway connecting a loop at the {beta}-ring interface to the S pockets of the opposing ring. More broadly, this work establishes a framework for resolving symmetry-masked allostery in multi-subunit assemblies. Significance StatementThe 20S proteasome is essential for the survival and virulence of Mycobacterium tuberculosis, yet how its catalytic sites communicate has been difficult to study because the bacterial enzyme is built from identical subunits whose signals are indistinguishable by conventional methods. Here we find that blocking only a fraction of these sites by inhibitors paradoxically activates the enzyme, revealing positive cooperativity between neighbouring subunits. To trace the communication pathways, we developed an isotopic-coding strategy that enables hydrogen/deuterium exchange mass spectrometry report on individual subunits within a single symmetric complex. This approach maps how ligand binding at one subunit reshapes its neighbours and, more broadly, provides a general framework for dissecting allostery in homomeric molecular machines whose symmetry has long obscured it.

biochemistry↗

bioRxiv2026

Multiple pathways couple kinetochore orientation to the meiotic spindle cycle

Meiosis generates haploid gametes from a diploid progenitor. In meiosis I, homologous chromosomes segregate while sister chromatids co-orient toward the same spindle pole. The mechanisms underlying this specialized segregation pattern remain incompletely understood. Here we identify pathways required for meiosis I chromosome segregation through a forward genetic screen in Saccharomyces cerevisiae. We find that meiosis I is highly sensitive to perturbations in diverse components of the segregation machinery and define key functional interfaces within complexes important for this division. These include meiosis I-specific regulators that establish the specialized chromosome pattern, namely the monopolin complex that directs sister kinetochore co-orientation and the Spo13MOKIR-Cdc5Polo module that promotes meiosis I chromosome segregation. In addition, we identify mutations affecting the core segregation machinery, including the spindle pole body, spindle midzone, and outer kinetochore, which can disrupt coupling between the chromosome segregation program and the meiotic spindle cycle. Together, our findings reveal that multiple pathways coordinate chromosome segregation with the meiotic divisions and highlight the unique demands of meiosis I.

cell biology↗

bioRxiv2026

Senescent myoblasts exhibit ROS-dependent Akt-mTORC1 dysregulation and are susceptible to reductive stress-induced cell death.

Ageing is characterised by the accumulation of senescent cells. Owing to their irreversible cell-cycle arrest, these cells lack the capacity to replenish the stem cell pool and regenerate tissue, while their pro-inflammatory secretome propagates senescence in a paracrine manner. Much of the senescent phenotype has been attributed to dysregulated mTORC1 signalling, a key regulator of protein synthesis implicated in organismal ageing. Nonetheless, the mechanism underlying this dysregulation is poorly understood and limited to a few selected cell types. Here, we show that mTORC1 dysregulation is also a characteristic of senescent muscle precursor cells, and in contrast to reports in other cell types, senescent myoblasts do not rely on lysosomal nutrient liberation to sustain mTORC1 activity. Instead, they appear to depend on the PI3K/Akt pathway, which is upregulated in these cells. Exogenous antioxidants were identified to alleviate PI3K/Akt/mTORC1 signalling, while exogenous ROS has the capacity to activate mTORC1, supporting a model in which ROS acts upstream of this pathway in senescent myoblasts. Moreover, antioxidants were able to suppress the expression of pro-inflammatory cytokines and enhance the differentiation of senescent myoblasts. Interestingly, prolonged antioxidant treatment led to increased cell death in senescent but not proliferating myoblasts, suggesting they are more prone to reductive stress-induced cell death. We propose that, in vitro, the antioxidant capacity of many plant-derived compounds may underlie their reported benefits as therapeutics targeting senescent cells (senotherapeutics). Together, our findings provide novel insights into mTORC1-dependent regulation of the senescent phenotype and highlight the role of redox modulation in senotherapeutic strategies.

cell biology↗

bioRxiv2026

The Signal in the Noise: Hierarchy and Robustness of Physiological Audience Alignment during Narrative Media

Communication research traditionally prioritizes receiver variance, often overlooking how a single message induces commonality across distinct systems. Drawing on classical theory, we propose that effective messages entrain the biological rhythms of the audience. In a large-scale experiment (N=198) monitoring eye-tracking, heart rate, and electrodermal activity during a film, we mapped this alignment. Results reveal a processing hierarchy: alignment was strongest for information acquisition (gaze) but also extended to downstream autonomic regulation. Crucially, a temporal manipulation confirmed this state is content-locked: alignment vanished when the narrative sequence was altered but was restored upon computational unscrambling of the physiological time series. This confirms that responses carry a temporal fingerprint of the content. We conclude that messages function as alignment devices, reducing individual noise to create a network of receivers exhibiting shared processing states, thus providing a materially grounded, signal-based definition of the audience.

animal behavior and cognition↗

bioRxiv2026

Expression and role of the RNA-binding protein, ZFP36L1, in mouse T follicular helper cell differentiation and function

T follicular helper (Tfh) cells are critical for germinal centers (GC), the specialised microenvironment where long-lived humoral immunity is generated in response to vaccination or infection. Within the GC, B cells engage with Tfh cells and elicit their help in the form of cytokines and cell-surface co-stimulator molecules. Tfh helper activity must be rapidly available in response to B cell engagement, yet the mechanisms controlling this helper activity remain poorly characterized. Post-transcriptional regulation of mRNA decay and translation offer one way to rapidly and temporally tune Tfh cell activity. ZFP36L1, a member of the ZFP family of RNA-binding proteins, is a candidate modulator of Tfh cell helper activity as it controls cytokine production and responses in other T cell lineages, modulating their differentiation and function. We sought to determine if ZFP36L1 is also important for Tfh cell biology. In this study, we show expression of ZFP36L1 by Tfh cells. We selectively delete ZFP36L1 from Tfh cells and analyze the effect this has on the GCs. Surprisingly, we find the GC response and affinity maturation is resilient to deletion of ZFP36L1 from Tfh cells.

immunology↗

bioRxiv2026

Serum Proteomic Profiling Implicates a Dysregulated Neurohormonal-Inflammatory Axis in Post-Fontan Tachycardia

BackgroundPost-operative tachycardia is a common and poorly understood complication following the Fontan procedure. Post-operative factors such as surgical scarring and venous hypertension can contribute to tachycardia risk, but the specific molecular signaling cascades triggering acute tachycardia remain uncharacterized, limiting therapeutic innovation and leaving clinicians with only reactive management strategies. Here, we present a retrospective translational study leveraging serum proteomics and machine learning to identify the molecular drivers of post-operative Fontan tachycardia. MethodsWe integrated a clinically relevant ovine animal model of the Fontan circulation with continuous telemetric heart rate monitoring and human patient data. Serum proteomics coupled with machine learning algorithms (LASSO and Boruta) were employed to identify protein panels predictive of post-operative tachycardia. Cross-species validation was performed by comparing proteomic signatures from sheep and pediatric patients undergoing Glenn or Fontan surgery. ResultsOvine Fontan animals demonstrated significant heart rate elevation beginning on post-operative day (POD) 1, peaking at POD 3 (159.4 {+/-} 11.7 bpm vs. pre-operative 105.3 {+/-} 10.5 bpm, p<0.0001), before trending toward baseline by POD 10. This pattern was mirrored in human pediatric patients, though with a more modest magnitude. Surgical controls did not exhibit tachycardia, indicating the response was specific to the Fontan procedure. Proteomic analysis identified distinct separation between pre- and post-operative serum profiles. Principal component analysis revealed that the principal components most correlated with heart rate (PC1: r=0.79, p=6.5x10-; PC8: r=0.40, p=0.04) were significantly enriched for inflammatory and neural pathways. We leveraged the Boruta algorithm to identify a seven-protein panel (ACE, ANGT, ITIH4, SELENOP, W5PHP7, PTX3, and F5) with superior predictive power (AUC=0.926). A cross-species comparison between human and sheep demonstrated that three proteins, angiotensinogen (ANGT), angiotensin-converting enzyme (ACE), and pentraxin 3 (PTX3), were similarly dysregulated in both species post-operatively. ConclusionsThis study provides the first direct molecular evidence implicating a dysregulated neurohormonal-inflammatory axis as a principal driver of acute post-operative Fontan tachycardia. The identified protein signature offers novel mechanistic insights and establishes a foundation for developing targeted diagnostics and therapeutics to predict and mitigate this significant clinical complication.

bioinformatics↗

bioRxiv2025

The Structural Basis of Pacs1-Wdr37 Complex Assembly and Stability

Phosphofurin acidic cluster sorting protein 1 (Pacs1) is a multidomain adaptor proposed to bind transmembrane cargo proteins to facilitate their intracellular trafficking. Pacs1 also forms a complex with WD-repeat protein 37 (Wdr37), which is essential for lymphocyte homeostasis. Despite numerous proposed binding partners, a validated structure for Pacs1-containing protein complexes is lacking. Here, we present the cryo-electron microscopy structure of the Pacs1-Wdr37 complex. Pacs1 binds Wdr37 through a conserved interface within its furin-binding region (FBR), the domain previously linked to cargo recognition. This interaction stabilizes Wdr37 and is critical for the expression of both proteins. A gain-of-function mutation in PACS1 (R203W) causes a highly penetrant neurodevelopmental syndrome. This pathogenic mutation lies on a solvent-exposed surface of the FBR and does not disrupt complex formation. Instead, Pacs1-R203W remains dependent on Wdr37 for stability and its levels can be reduced through targeted Wdr37 proteolytic degradation. Structural homology of the FBR to synaptotagmin C2 domains reveals a previously unrecognized ability of Pacs1 to bind negatively charged phospholipids through a unique positively charged cleft. Together these findings define the structural basis for Pacs1-Wdr37 complex assembly and stability, present potential strategies for Pacs1-mediated neurodevelopmental disease, and suggest novel Pacs1 functions in membrane association.

biochemistry↗

bioRxiv2025

Differential regulation of TCR-induced ZFP36 and ZFP36L1 expression by cyclosporin A in CD8+ T cells

CD8+ T cells target infected or malignant cells via the production of pro-inflammatory cytokines and direct target cell killing. Members of the ZFP36-family of RNA binding proteins, ZFP36 and ZFP36L1 regulate these functions in T cells via the regulation of mRNA stability and protein translation. We investigate the regulation of ZFP36 and ZFP36L1 expression using in vitro differentiated OT1 TCR transgenic memory-like T cells. We characterise the differential kinetics and sensitivity of ZFP36 and ZFP36L1 to antigen affinity and PMA versus ionomycin stimulation. By selectively inhibiting TCR-induced signalling pathways, we find that p38 MAPK, MEK1/2 and PKC contribute to inducing both ZFP36 and ZFP36L1 expression. By contrast, inhibition of calcineurin using cyclosporin A potently inhibits ZFP36L1 expression while increasing and prolonging ZFP36 expression. The Zfp36 promoter contains many binding sites for the transcription factors ELK-1/4 and few binding sites for NFAT, while the Zfp36l1 promoter contains many NFAT binding sites and few ELK1/4 binding sites. Our findings suggest that regulation of divergent transcription factors enable calcineurin to act as a signalling node that mediates the differential regulation of ZFP36 and ZFP36L1 during T cell activation.

immunology↗

bioRxiv2025

A post-transcriptional regulatory checkpoint controls the response of tumor-infiltrating cytotoxic CD4+ T cells to immunotherapy

Acquisition of cytotoxic activity in CD4+ T cells (TCTX) can promote potent anti-tumor activity thus holding promise as a therapeutic approach. However, how this activity is regulated remains poorly understood. Here, we demonstrate that tumor-infiltrating CD4+ TCTX activity is restrained by a post-transcriptional regulatory checkpoint. In untreated tumors, CD4+ TCTX exist in a poised state, characterized by abundant Gzmb mRNA but limited Granzyme B (GzmB) protein. Differentiation into poised TCTX is regulated by the Blimp-1-Bcl6 axis and requires type-I interferon signaling. Treatment with anti-CTLA-4 or anti-LAG-3 plus anti-PD-1 removed the block to GzmB protein production by repressing expression of the post-transcriptional regulator Zfp36l1. Constitutive Zfp36l1 expression abrogated the effects of anti-CTLA-4 while deletion of Zfp36l1 and its paralog Zfp36 triggered GzmB protein production and promoted tumor control. These data identify ZFP36/ZFP36L1 as a key post-transcriptional regulatory checkpoint of CD4+ TCTX activity and a potential immunotherapy target in cancer.

immunology↗

bioRxiv2025

Mutation or deletion of the Avr6 avirulence effector gene of Fulvia fulva leads to breakdown of the Cf-6 leaf mold resistance locus in tomato

Genetic resistance mediated by Cf cell-surface receptors is a cornerstone of tomato breeding against leaf mold disease caused by the fungal pathogen Fulvia fulva. After widespread deployment of the Cf-9 resistance locus, breeders increasingly relied on Cf-6, yet Cf-6-mediated resistance has already been overcome in multiple regions. The molecular basis of this breakdown, and the identity of the matching avirulence (Avr) effector, have remained unresolved. Here, we use comparative genomics and functional genetics to identify the F. fulva effector Avr6 as the previously described apoplastic protein Ecp5. Sequencing of Cf-6-breaking strains revealed either deletion of the Ecp5 locus or non-synonymous mutations in its coding sequence. Using transient expression, targeted gene knockout, and complementation assays, we show that Ecp5 is both necessary and sufficient for Cf-6-mediated recognition and defence activation. We then use Avr6-triggered cell death as a phenotypic marker in a bulked segregant analysis combined with Comparative Subsequence Sets analysis (CoSSa) to map Cf-6 to a [~]2 Mb interval on the short arm of chromosome 12 that overlaps the previously described Cf-Ecp5.12 locus. Sequencing of Avr6 in a broad strain collection reveals a predominantly conserved allele under apparent purifying selection, with recent independent loss-of-function variants in Europe and South America that confer virulence on Cf-6 plants. Together, these findings establish the Avr6-Cf-6 gene-for-gene pair, explain the erosion of Cf-6-mediated resistance, and illustrate how effector loss or mutation provides a rapid route for F. fulva adaptation, with important implications for designing more durable resistance strategies against tomato leaf mold.

microbiology↗

bioRxiv2025

Decreased female survival may explain wild turkey decline

Recent declines in wild turkey (Meleagris gallopavo) populations have prompted extensive research efforts and adjustments to state hunting regulations across the range of wild turkeys. However, research comparing historical and modern vital rates is needed to identify demographic factors that may explain declines. Based on matrix models, adult female survival has the greatest effect on the intrinsic rate of growth. Thus, we hypothesized that changes in annual female survival may explain contemporary declines in populations if that vital rate has decreased concomitant with population declines. We searched peer-reviewed literature, student theses and dissertations, and government reports for empirical estimates of annual female survival across the range of wild turkeys. Of the 51 resulting estimates of annual female survival across all subspecies, most were [≥]0.6 through 2012, but 8 out of 10 estimates post-2012 were lower, consistent with observed trends in population trajectories. We used matrix models to illustrate that the observed change in annual female survival estimates indeed predicts a declining population trajectory, even when other important vital rates are at the high end of the published range of process variation. If the published annual female survival estimates represent those experienced more broadly in populations, our meta-analysis and matrix models indicate that decreases in this vital rate help explain declines observed in populations in some regions. The causative factor(s) associated with the apparent declines are unknown, and little research has evaluated management strategies to increase annual female survival. Accordingly, we encourage wild turkey researchers to focus efforts on producing robust estimates of annual female survival, cause-specific mortality, and rigorous evaluation of management strategies to improve annual female survival.

zoology↗

bioRxiv2025

Loss of the autism associated gene Tbr1 disrupts prediction and encoding by prefrontal ensembles during socioemotional behaviors

Disruptions in many genes linked to autism spectrum disorder (ASD) affect synaptic function and socioemotional behaviors in mice. However, exactly how synaptic dysfunction alters neural activity patterns underlying behavior remains unknown. We addressed this using mice lacking the high confidence ASD gene Tbr1 in cortical layer 5 (L5) projection neurons (Tbr1 cKO mice). These mice have known deficits in synaptic input to L5 neurons and social behavior. We also find some abnormalities in anxiety-related avoidance. Calcium imaging of prefrontal L5 neurons revealed that despite reduced overall activity, cKO mice recruit normal numbers of neurons into prefrontal ensembles encoding social and anxiety-related behaviors. However, the stability, inter-neuronal coordination, and reactivation of social ensembles were diminished in cKO mice. Furthermore, in cKO mice, ensembles no longer predicted approach-avoidance decisions. These results reveal new aspects of how prefrontal ensembles encode socioemotional behaviors, and malfunction in the setting of ASD-linked gene disruption.

neuroscience↗

bioRxiv2024

RNA-binding proteins control the G2-M checkpoint of the germinal centre B cell

How germinal centre (GC) B cells undergo rapid cell division while maintaining genome stability is poorly understood. Here, we show that the RNA-binding proteins ZFP36L1 and ZFP36L2 act downstream of antigen-sensing and protect GC B cells from replication stress by controlling a cell cycle-related RNA post-transcriptional regulon. ZFP36L1 and ZFP36L2 safeguard faithful completion of mitosis by restraining the expression of CDK1 and cyclin B1, whilst controlling their activity through regulation of a p21-mediated negative feedback loop. In the absence of ZFP36L1 and ZFP36L2, GC B cells arrest in G2-M and die by apoptosis, resulting in curtailed GC responses. This is associated with stalling of the DNA replication fork at active replication initiation zones, which causes replication stress and increased activity of the ATR/CHK1 DNA damage response. Our findings reveal that gene regulation by RNA-binding proteins is essential for a functional G2-M checkpoint to operate in GC B cells.

immunology↗

bioRxiv2024

Structural basis for allosteric regulation of the proteasome core particle

Intracellular protein degradation is vital across all domains of life1. In eukaryotes, the ubiquitin proteasome system performs most non-lysosomal protein degradation and influences numerous cellular processes. Some bacteria, including the human pathogen Mycobacterium tuberculosis (Mtb), encode a proteasome system that selectively degrades damaged or misfolded proteins crucial for the pathogens survival within host macrophages2-7. Consequently, the 20S core particle (CP), the central component of the proteasome system, has emerged as a viable target for tuberculosis treatment strategies2,8-10. Both eukaryotic and Mtb proteasome systems are allosterically regulated11-13, yet the specific conformations involved have not been captured in high-resolution structures to date. Here we present the first structure of Mtb 20S CP, and indeed any 20S CP, in an inactive state called 20SOFF, distinguished from the canonical active state, 20SON, by the conformation of switch helices I and II. The rearrangement of these helices collapses the S1 pocket, effectively inhibiting substrate binding. The switch helices are conserved and regulate the activity of HslV protease, the proteasomes ancestral enzyme in bacteria, and a diverse family of serine/threonine protein phosphatases. Our results highlight the potential of harnessing allostery to develop therapeutics against the 20S CP in Mtb and eukaryotic systems.

biochemistry↗

bioRxiv2024

Design, infectability, and transcriptomic analysis of transregionally differentiated and scalable lung organoids derived from adult bronchial cells.

The lung is a primary target for many lethal respiratory viruses, leading to significant global mortality. Current organoid models fail to completely mimic the cellular diversity and intricate tubular and branching structures of the human lung. Lung organoids derived from adult primary cells have so far only included cells from the input cell region, proximal or distal. Existing models are expensive. They often require cells from invasive deep lung tissue biopsies. The present study aimed to address these limitations. The lung organoids obtained using an original protocol exhibited transregional differentiation and were derived from relatively more accessible primary cells from the trachea/bronchi. Immortal bronchial cell lines were also used to simplify organoid fabrication and improve its scalability. The lung organoids are formed starting from bronchial cells with fibroblasts feeder cells in an alginate hydrogel coated with base membrane zone proteins. Characterizations were performed using bulk RNA sequencing and tandem mass tags. The resulting organoids express markers of different lung regions and mimic to some extent the tubular and branching morphology of the lung. The proteomic profile of organoid from primary cells and from cell lines was found to evolve towards that of mature lung tissue. Upregulated genes were mostly related to the respiratory system, tube development, and various aspects of respiratory viral infections. Infection with SARS-CoV-2 and influenza H1N1 was successful and did not require organoid disassembly. The organoids matured within 21 days and did not require complex or expensive culture methods. Transregionally differentiated lung organoid may find applications for the study of emerging or re-emerging viral infections and fostering the development of novel in-vitro therapeutic strategies.

cell biology↗

bioRxiv2024

Sex-specific sequels of early life stress on serine/threonine kinase activity in visceral adipose tissue from obese mice

Adverse childhood experiences (ACEs) are an established independent risk factor for chronic disease development including obesity and hypertension; however, only women exposed to ACEs show a positive relationship with BMI. Our lab has reported that maternal separation and early weaning (MSEW), a mouse model of early life stress, induces sex-specific mechanisms underlying greater blood pressure response to a chronic high fat diet (HF). While female MSEW mice fed a HF display exacerbated perigonadal white adipose tissue (pgWAT) expansion and a metabolic syndrome phenotype compared to controls, male MSEW mice display similar levels of adiposity compared to control counterparts but display neurogenic hypertension. Thus, this study aimed to determine a pgWAT whether there is a sex-specific serine/threonine kinase (STKA) activity associated with early life stress. Frozen pgWAT was collected from MSEW and Control, male and female mice fed a HF to assess STKA activity using the Pamstation12 instrument. Overall, MSEW induces significant reduction of 7 phosphokinases (|Z| >=1.5) in females (QIK, MLK, PKCH, MST, STE7, PEK, FRAY) and 5 in males (AKT, SGK, P38, MARK, CDK), while 15 were downregulated in both sexes (DMPK, PKA, PKG, RSK, PLK, DYRK, NMO, CAMK1, JNK, PAKA, RAD53, ERK, PAKB, PKD, PIM, AMPK). This data provides new insights into the sex-specific dysregulation of the molecular network that regulates cellular phosphorylation signals in visceral adipose tissue and identifies possible target phosphokinases important in adipocyte hypertrophy as a result of exposure to early life stress combined with an unhealthy. Identifying functional metabolic signatures associated with early life stress is critical to elucidate the underlying molecular mechanisms behind the sex-specific obesity risk.

molecular biology↗

bioRxiv2024

Reconfigurable multi-component nanostructures built from DNA origami voxels

In cells, proteins rapidly self-assemble into sophisticated nanomachines. Bio-inspired self-assembly approaches, such as DNA origami, have achieved complex 3D nanostructures and devices. However, current synthetic systems are limited by lack of structural diversity, low yields in hierarchical assembly, and challenges in reconfiguration. Here, we develop a modular system of DNA origami voxels with programmable 3D connections. We demonstrate multifunctional pools of up to 12 unique voxels that can assemble into many shapes, prototyping 50 structures. Multi-step assembly pathways with sequential reduction in conformational freedom were then explored to increase yield. Voxels were first assembled into flexible chains and then folded into rigid structures, increasing yield 100-fold. Furthermore, programmable switching of local connections between flexible and rigid states achieved rapid and reversible reconfiguration of global structures. We envision that foldable chains of DNA origami voxels can be integrated with scalable assembly methods to achieve new levels of complexity in reconfigurable nanomaterials.

synthetic biology↗