Biology subjects

Maes, A.

Publications and source records attributed to Maes, A..

15 recordsLinked to original sources

bioRxiv2026

Studying the regulons of OmrA and OmrB paralogous small RNAs reveals targets involved in central carbon metabolism and lipogenesis

Small regulatory RNAs (sRNAs) are key players in bacterial adaptation to stress. They often occupy central positions in regulatory networks and control the expression of multiple targets. In a striking example of this, the enterobacterial OmrA and OmrB paralogous sRNAs are known to regulate about ten different targets, with extensive data suggesting the regulon is in fact much larger. Here we performed transcriptome and proteome analyses and identified more than fifteen new targets of Escherichia coli OmrA and OmrB. We validated several, including genes involved in central carbon metabolism and fatty acid synthesis, among which ppc, actP and fabA. Consistent with a role in carbon metabolism, overproducing OmrA or OmrB inhibited growth on glucose minimal medium. The analysis of suppressor mutants shows that this is due to a decreased carbon flux through the TCA cycle. Incorporating other datasets such as RIL-seq, we generated a multi-omics-based prediction of target candidates. Together, our results show that OmrA/B base-pair to various regions of their mRNA targets, and therefore likely act through diverse regulatory mechanisms. Hence, this work extends the OmrA and OmrB regulons, establishes an unsuspected connection with carbon usage, and shows the benefits of combining global analyses to investigate sRNA regulons.

Molecular Biology↗

bioRxiv2026

RNase J2 is a specificity factor that governs global mRNA stability in Bacillus subtilis

Ribonucleases (RNases) play a key role in modulating gene expression at the post-transcriptional level, enabling bacteria to rapidly adapt to their environment. The B. subtilis genome encodes more than 20 RNases and understanding the role of each of these enzymes is crucial for a comprehensive knowledge of bacterial post-transcriptional adaptation mechanisms. Among these, RNase J1 and J2, belonging to the {beta}-lactamase enzyme family, form a heterodimer. While the primary function of RNase J1 as a 5'-exoribonuclease in B. subtilis has been known for some time, the role of RNase J2, encoded by the rnjB gene, has remained unclear. Indeed, it has been considered a minor degradation factor due its very weak 5'-exoribonuclease in vitro, the lack of a growth phenotype and the limited number of mRNAs with altered equilibrium levels in rnjB mutants. In this study, we demonstrate that the absence of RNase J2 influences pellicle and macro-colony biofilm formation, as well as swarming in B. subtilis. We show that RNase J2 plays a far more global role in governing mRNA half-lives than originally thought, by stimulating RNase J1-mediated degradation of a subset of RNase J1's mRNA substrates. An inter-subunit contact between RNase J1 and J2 is crucial for RNase J2 action. Altogether, our results suggest that RNase J2 acts primarily as a specificity co-factor for RNase J1 rather than as a ribonuclease per se.

microbiology↗

bioRxiv2026

Structural basis of HSP90C, a highly active chloroplastic HSP90 chaperone from A. thaliana

Chloroplasts are the main energy organelles in plants, primary through photosynthesis. Thereby, they are responsible for CO2 fixation and dioxygen production, which are essential for living species on Earth. To ensure these processes, numerous proteins encoded from the nuclear DNA need to be imported inside the chloroplast, and eventually to the thylakoids. Whereas the translocation systems from both chloroplastic and thylakoids membranes have been studied in recent years, the stromal route between these two membranes is largely unknown. Notably, the chloroplastic HSP90 (HSP90C) is likely to play an important role in this process, but its structure and molecular mechanisms remain to be unveiled. In this study, we used a combination of structural and biophysical approaches to elucidate the features of Arabidopsis thalianas HSP90C. Principally, we found that HSP90C has a remarkably high ATPase activity among the HSP90 family proteins. Further investigation allowed us to pinpoint atypical mechanisms responsible for this high activity. First, the N-terminal cap is involved in a disulfide bond that accelerates the ATPase activity of HSP90C. Second, its C-terminal domain features an extension that is mandatory for its dimerization. Third, our crystal structures reveal a wide opening of the HSP90Cs dimer with reduced intermonomeric interfaces. Lastly, we identified a helical switch which is required for HSP90Cs high activity. Three of these four features are due to sequence signatures of HSP90C, which we found to be shared by most of green plants representatives. Our study provides first insights of HSP90Cs non-canonical mechanisms, which will help in the understanding of processes related to protein import in the chloroplast.

biochemistry↗

bioRxiv2025

A photoprotection dial maps holistic light-stress response in diatoms

Cellular responses to light stress operate on two timescales: short-term responses, driven by dynamic photosynthetic mechanisms such as non-photochemical quenching (NPQ), and long-term responses, characterized by various physiological and metabolic shifts driven by changes in gene expression. Understanding the coordination within and between these layers represents a major challenge in photosynthesis research. We achieved this in the diatom Phaeodactylum tricornutum using an adjustable "photoprotection dial" across 10 mutant strains expressing different constitutive levels of the Lhcx1 protein, which determine their latent NPQ capacity. Crucially, a near-identical initial state is preserved among strains, which allows a precise mapping of the causal chain of events initiated by NPQ induction under high light. This unlocks exceptional leverage to examine holistic interactions between functional photosynthesis and gene expression within their natural regulatory architecture. We observe that increasing NPQ maintains the PSII primary acceptor QA in a more oxidized state with little effect on linear electron flow. This oxidation limits PSII photodamage and promotes cyclic electron flow around PSI, which in turn is consistent with enhanced ATP production supporting PSII repair. Moreover, transcriptomic analysis across high-light exposure time suggests that the expression of nearly half of the genome is modulated via NPQ-driven effects. Gene expression profile clustering reveals distinct and coherent transcriptomic regulatory networks. The short-term response is characterized by a strong downregulation of light-harvesting-related genes -- independently of NPQ -- and an upregulation of oxidative stress response genes that scales inversely with NPQ magnitude. In the long term, most of the transcriptome is deeply impacted by high-light stress in a widely NPQ-dependent manner, highlighting the critical role of this process in shaping photophysiology, which in turn influences gene expression. By engineering a native functional feedback loop into an experimental dial, our approach establishes a generalizable framework for studying the complex interplay between physiology and system-wide biological regulation.

plant biology↗

bioRxiv2025

From injury to recovery: Functional neuronal regeneration after traumatic brain injury in the telencephalon of the young adult African turquoise killifish

Neuronal loss caused by neurodegenerative diseases and traumatic brain injuries (TBI) often results in long-term disabilities, highlighting the urgent need for further research and effective regenerative strategies. In mammals, neurogenic capacity is inherently limited and declines further with age. In contrast, the young adult killifish demonstrates a remarkable ability to regenerate neurons in the telencephalon following TBI. However, it remains unknown whether and when these newly generated neurons functionally integrate into existing circuits, as traditional histological analysis of fixed tissue offers only static insights into this dynamic process. To this end, we optimized a retroviral vector strategy to label dividing stem cells and their progeny, including newborn neurons. By introducing a combination of novel approaches i.e., retroviral vector labeling, electrophysiology and a conditioned place avoidance test, we investigated the generation, morphology, and synaptic integration of newborn neurons following TBI in the dorsomedial (Dm) zone of the telencephalon, a region homologous to the mammalian amygdala in other teleost fish. Our results show that injury-induced adult-born neurons functionally integrate into existing circuits, and that killifish can achieve functional behavioral recovery after TBI. While previous histological assessments using a stab-wound injury suggested a 30-day recovery period, our functional data reveal that full behavioral recovery requires approximately 50 days. At this point, fish successfully relearn to avoid a conditioned place, and the new neurons exhibit mature morpho-electric characteristics, including abundant dendritic spines. Electrophysiological analysis revealed that newborn neurons in an injured environment take longer to mature when compared to neurons in naive killifish. Together, our findings demonstrate that structural regeneration aligns with functional recovery, and establish retroviral vectors as a powerful tool for birth dating injury-induced neurogenesis in teleosts. Killifish thus represent a promising model for studying interventions aimed at enhancing neuronal maturation and integration after brain injury. Key pointsO_LIA retroviral vector strategy allows specific and sparse labeling of adult-born neurons in the killifish brain. C_LIO_LIThe Dm zone in the telencephalon of the killifish is responsible for avoidance learning and memory and thus homologous to the mammalian amygdala. C_LIO_LIIn young adult killifish, upon Dm injury, adult-born neurons mature morphologically and functionally in 50 days, which is slower than in constitutive neurogenesis. C_LIO_LIThe timing and extent of behavioral recovery from such injury aligns with morpho-electric observations. C_LI

neuroscience↗

bioRxiv2025

30S-seq redefines the bacterial Ribosome Binding Site

The translation initiation step is rate limiting for the efficiency of gene expression in all organisms. However, the mechanism of ribosome recruitment to mRNA start sites strikingly differs between eukaryotes and prokaryotes. The eukaryotic small (40S) ribosomal subunit binds 5 end caps and scans for the start codon while the bacterial small (30S) subunit directly binds to the Shine-Dalgarno (SD) motif close to the initiation site. Pioneer studies have shown rare 30S loading events further upstream within 5 untranslated regions (5UTRs), at ribosome standby sites1-3. Together with the frequent occurrence of long bacterial mRNA 5UTRs and degenerated SD sequences, this indicates that the 30S subunit might bind upstream of the SD more commonly than currently thought. We therefore developed 30S-seq to map 30S-mRNA interactions in a bacterial transcriptome (Escherichia coli), inspired by translation complex profile sequencing (TCP-seq) previously used in eukaryotes4,5. Our results provide new and unsuspected insights into the behaviour of 30S and 70S complexes during the canonical translation initiation process. Notably, 30S subunits are recruited upstream of the start codon, primed to receive the SD released by the departing 70S ribosome. Remarkably, we also find hundreds of non-canonical 30S binding sites within mRNA 5UTRs, sometimes over 100 nucleotides upstream of the start region. We validated several of these upstream ribosome binding sites, and demonstrated their strong impact on gene expression. Thus, even in bacteria, ribosomes frequently bind mRNAs outside of the start region to initiate translation, challenging the classic ribosome binding site model.

molecular biology↗

bioRxiv2025

The shortest telomere in telomerase-negative cells triggers replicative senescence at a critical threshold length and also fuels genomic instability

In the absence of telomerase, telomere shortening triggers replicative senescence, a tumor suppressor mechanism that is also associated with oncogenic genomic instability. Yet, the precise mechanism that connects these seemingly opposing forces remains poorly understood. To directly study the complex interplay between senescence, telomere dynamics, and genomic instability, we developed a system in Saccharomyces cerevisiae to generate and track telomeres of precise length in the absence of telomerase. Using single-telomere and single-cell analyses combined with mathematical modeling, we identify a threshold length at which telomeres switch into dysfunction. A single shortest telomere below the threshold length is necessary and sufficient to trigger the onset of replicative senescence in a majority of cells. At population level, fluctuation assays establish that rare genomic instability arises predominantly in cis to the shortest telomere as Pol32-dependent non-reciprocal translocations that result in re-elongation of the shortest telomere and likely transient escape from senescence. The switch of the shortest telomere into dysfunction and subsequent processing in telomerase-negative cells thus serves as the mechanistic link between replicative senescence onset, genomic instability and the initiation of post-senescence survival.

molecular biology↗

bioRxiv2024

Unconventional mRNA processing and degradation pathways for the polycistronic yrzI mRNA in B. subtilis

The ribosome-associated endoribonuclease Rae1 cleaves the Bacillus subtilis yrzI operon mRNA in a translation-dependent manner. This operon encodes up to four small peptides, S1027, YrzI, S1025 and S1024, whose functions were unknown. We show that YrzI is toxic at high concentrations, but co-expression with S1025 abolishes its toxicity. We show that a highly stable mRNA species containing the YrzI and S1025 open reading frames results from endoribonucleolytic cleavage upstream of the yrzI ORF followed by 5-exoribonucleolytic processing arrested by ribosomes bound to its exceptionally strong Shine-Dalgarno sequence. Degradation of this mRNA requires either translation-dependent cleavage within S1025 by Rae1 or direct attack from the structured 3-end by 3-exoribonucleases. Both pathways are atypical for a B. subtilis mRNA.

molecular biology↗

bioRxiv2024

Pathophysiological response in experimental trauma-related acute kidney injury

BackgroundTrauma and shock often severely affect the kidneys. This can lead to trauma-related acute kidney injury (TRAKI), which significantly increases the risk of adverse outcomes. MethodsTo study the pathophysiology of TRAKI, we developed a murine model of combined blunt thoracic trauma and pressure-controlled hemorrhage that induces mild transient TRAKI. ResultsThe mice showed early and transient increased plasma creatinine, urea, NGAL, and urine albumin, resolving 5 days after TRAKI induction. Despite normal kidney morphology, significant damage to proximal tubular cells and a loss of the brush border was observed. This included kidney stress responses, e.g., with induced heme oxygenase-1 expression in tubules. The upregulation of inflammatory mediators and kidney injury markers was followed by elevated leukocyte numbers, mainly consisting of monocytes/macrophages. Proteomic analyses revealed a distinct time course of intrarenal processes after trauma. 3D x-ray-based whole-organ histology by contrast-enhanced microcomputed tomography showed significant impairment of capillary blood flow, especially during the first day post THS, which was partly resolved by day 5. ConclusionsOur novel model of murine TRAKI has revealed previously unknown aspects of the complex temporal pathophysiological response of the kidney along the nephron after trauma and hemorrhage, which may provide mechanistic starting points for future therapeutic approaches.

pathology↗

bioRxiv2024

A parabrachial hub for the prioritization of survival behavior

Long-term sustained pain in the absence of acute physical injury is a prominent feature of chronic pain conditions. While neurons responding to noxious stimuli have been identified, understanding the signals that persist without ongoing painful stimuli remains a challenge. Using an ethological approach based on the prioritization of adaptive survival behaviors, we determined that neuropeptide Y (NPY) signaling from multiple sources converges on parabrachial neurons expressing the NPY Y1 receptor to reduce sustained pain responses. Neural activity recordings and computational modeling demonstrate that activity in Y1R parabrachial neurons is elevated following injury, predicts functional coping behavior, and is inhibited by competing survival needs. Taken together, our findings suggest that parabrachial Y1 receptor-expressing neurons are a critical hub for endogenous analgesic pathways that suppress sustained pain states.

neuroscience↗

bioRxiv2022

La revolution de l'ADN: biocompatible and biosafe DNA data storage

DNA data storage is an emerging technology that has the potential to replace bulky, fragile and energy-intensive current digital data storage media. Here, we report a storage strategy called DNA Drive, that organizes data on long double stranded replicative DNA molecules. The DNA Drive has unlimited storage capacity, and its encoding scheme ensures the biosafety of the process by limiting the potential of the DNA sequence to code for mRNA and proteins. Using our approach, we encoded two historical texts from the French Revolution, the Declaration of the Rights of Man and of the Citizen of 1789 and the Declaration of the Rights of Woman and of the Female Citizen published in 1791. In contrast to previous DNA storage strategies, the biocompatibility of the DNA Drive enables biological manipulation of the data including low cost copy. One-Sentence SummaryThe DNA Drive is a biosafe and biocompatible DNA data storage strategy with unlimited storage capacity.

synthetic biology↗

bioRxiv2021

Long- and short-term history effects in a spiking network model of statistical learning

The statistical structure of the environment is often important when making decisions. There are multiple theories of how the brain represents statistical structure. One such theory states that neural activity spontaneously samples from probability distributions. In other words, the network spends more time in states which encode high-probability stimuli. Existing spiking network models implementing sampling lack the ability to learn the statistical structure from observed stimuli and instead often hard-code a dynamics. Here, we focus on how arbitrary prior knowledge about the external world can both be learned and spontaneously recollected. We present a model based upon learning the inverse of the cumulative distribution function. Learning is entirely unsupervised using biophysical neurons and biologically plausible learning rules. We show how this prior knowledge can then be accessed to compute expectations and signal surprise in downstream networks. Sensory history effects emerge from the model as a consequence of ongoing learning.

neuroscience↗

bioRxiv2021

Stress-induced collective behavior leads to the formation of multicellular structures and the survival of the unicellular alga Chlamydomonas

Depending on their nature, living organisms use various strategies to adapt to environmental stress conditions. Multicellular organisms implement a set of reactions involving signaling and cooperation between different types of cells. Unicellular organisms on the other hand must activate defense systems, which involve collective behaviors between individual organisms. In the unicellular model alga Chlamydomonas reinhardtii, the existence and the function of collective behavior mechanisms in response to stress remain largely unknown. Here we report the discovery of a mechanism of abiotic stress response that Chlamydomonas can trigger to form large multicellular structures that can comprise several thousand cells. We show that these aggregates constitute an effective bulwark within which the cells are efficiently protected from the toxic environment. We have generated the first family of mutants that aggregate spontaneously, the socializer mutants (saz), of which we describe here in detail saz1. We took advantage of the saz mutants to implement a large scale multiomics approach that allowed us to show that aggregation is not the result of passive agglutination, but rather genetic reprogramming and substantial modification of the secretome. The reverse genetic analysis we conducted on some of the most promising candidates allowed us to identify the first positive and negative regulators of aggregation and to make hypotheses on how this process is controlled in Chlamydomonas.

plant biology↗

bioRxiv2020

Learning compositional sequences with multiple time scales through a hierarchical network of spiking neurons

Sequential behaviour is often compositional and organised across multiple time scales: a set of individual elements developing on short time scales (motifs) are combined to form longer functional sequences (syntax). Such organisation leads to a natural hierarchy that can be used advantageously for learning, since the motifs and the syntax can be acquired independently. Despite mounting experimental evidence for hierarchical structures in neuroscience, models for temporal learning based on neuronal networks have mostly focused on serial methods. Here, we introduce a network model of spiking neurons with a hierarchical organisation aimed at sequence learning on multiple time scales. Using biophysically motivated neuron dynamics and local plasticity rules, the model can learn motifs and syntax independently. Furthermore, the model can relearn sequences efficiently and store multiple sequences. Compared to serial learning, the hierarchical model displays faster learning, more flexible relearning, increased capacity, and higher robustness to perturbations. The hierarchical model redistributes the variability: it achieves high motif fidelity at the cost of higher variability in the between-motif timings.

neuroscience↗

bioRxiv2019

Learning spatiotemporal signals using a recurrent spiking network that discretizes time

Learning to produce spatiotemporal sequences is a common task the brain has to solve. The same neural substrate may be used by the brain to produce different sequential behaviours. The way the brain learns and encodes such tasks remains unknown as current computational models do not typically use realistic biologically-plausible learning. Here, we propose a model where a spiking recurrent network of excitatory and inhibitory biophysical neurons drives a read-out layer: the dynamics of the recurrent network is constrained to encode time while the read-out neurons encode space. Space is then linked with time through plastic synapses that follow common Hebbian learning rules. We demonstrate that the model is able to learn spatiotemporal dynamics on a timescale that is behaviourally relevant. Learned sequences are robustly replayed during a regime of spontaneous activity.\n\nAuthor summaryThe brain has the ability to learn flexible behaviours on a wide range of time scales. Previous studies have successfully build spiking network models that learn a variety of computational tasks. However, often the learning involved is not local. Here, we investigate a model using biological-plausible plasticity rules for a specific computational task: spatiotemporal sequence learning. The architecture separates time and space into two different parts and this allows learning to bind space to time. Importantly, the time component is encoded into a recurrent network which exhibits sequential dynamics on a behavioural time scale. This network is then used as an engine to drive spatial read-out neurons. We demonstrate that the model can learn complicated spatiotemporal spiking dynamics, such as the song of a bird, and replay the song robustly.

neuroscience↗