Biology subjects

Schmidt, H.

Publications and source records attributed to Schmidt, H..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

The tree labeling polytope: a unified approach to ancestral reconstruction problems

MotivationReconstructing unobserved ancestral states of a phylogenetic tree provides insight into the history of evolving systems and is one of the fundamental problems in phylogenetics. For a fixed phylogenetic tree, the most parsimonious ancestral reconstruction - a solution to the small parsimony problem - can be efficiently found using the dynamic programming algorithms of Fitch-Hartigan and Sankoff. Ancestral reconstruction is important in many applications including inferring the routes of metastases in cancer, deriving the transmission history of viruses, determining the direction of cellular differentiation in organismal development, and detecting recombination and horizontal gene transfer in phylogenetic networks. However, most of these applications impose additional global constraints on the reconstructed ancestral states, which break the local structure required in the recurrences of Fitch-Hartigan and Sankoff. ResultsWe introduce an alternative, polyhedral approach to ancestral reconstruction problems using the tree labeling polytope, a geometric object whose vertices represent the feasible ancestral labelings of a tree. This framework yields a polynomial-time linear programming algorithm for the small parsimony problem. More importantly, the tree labeling polytope facilitates the incorporation of additional constraints that arise in modern ancestral reconstruction problems. We demonstrate the utility of our approach by deriving mixed-integer programming algorithms with a small number of integer variables and strong linear relaxations for three such problems: the parsimonious migration history problem, the softwired small parsimony problem on phylogenetic networks, and the convex recoloring problem on trees. Our algorithms outperform existing state-of-the-art methods on both simulated and real datasets. For instance, our algorithm scales to trace routes of cancer metastases in trees with thousands of leaves, enabling the analysis of large trees generated by recent single-cell sequencing technologies. On a mouse model of metastatic lung adenocarcinoma, the tree labeling polytope allows us to infer simpler migration histories compared to previous results. AvailabilityPython implementations of the algorithms provided in this work are available at: github.com/raphael-group/tree-labeling-polytope.

bioinformatics↗

bioRxiv2025

Fast tumor phylogeny regression via tree-structured dual dynamic programming

MotivationReconstructing the evolutionary history of tumors from bulk DNA sequencing of multiple tissue samples remains a challenging computational problem, requiring simultaneous deconvolution of the tumor tissue and inference of its evolutionary history. Recently, phylogenetic reconstruction methods have made significant progress by breaking the reconstruction problem into two parts: a regression problem over a fixed topology and a search over tree space. While effective techniques have been developed for the latter search problem, the regression problem remains a bottleneck in both method design and implementation due to the lack of fast, specialized algorithms. ResultsHere, we introduce fastppm, a fast tool to solve the regression problem via tree-structured dual dynamic programming. fastppm supports arbitrary, separable convex loss functions including the{ell} 2, piecewise linear, binomial and beta-binomial loss and provides asymptotic improvements for the{ell} 2 and piecewise linear loss over existing algorithms. We find that fastppm empirically outperforms both specialized and general purpose regression algorithms, obtaining 50-450x speedups while providing as accurate solutions as existing approaches. Incorporating fastppm into several phylogeny inference algorithms immediately yields up to 400x speedups, requiring only a small change to the program code of existing software. Finally, fastppm enables analysis of low-coverage bulk DNA sequencing data on both simulated data and in a patient-derived mouse model of colorectal cancer, outperforming state-of-the-art phylogeny inference algorithms in terms of both accuracy and runtime. Availabilityfastppm is implemented in C++ and available as both a command-line interface and Python library at github.com/elkebir-group/fastppm.git.

bioinformatics↗

bioRxiv2024

Estimates of quantal synaptic parameters in light of more complex vesicle pool models

The subdivision of synaptic vesicles (SVs) into discrete pools is a leading concept of synaptic physiology. To better explain specific properties of transmission and plasticity, it has been suggested initially that the readily releasable pool (RRP) of SVs is subdivided into two parallel pools differing in their release probability. More recently, evidence was provided that sequential pools with a single RRP and a series-connected finite-size replacement pool (RP) inserted between the reserve pool (RSP) and RRP equally well or even better account for most aspects of transmission and plasticity. It was further suggest that a fraction of the presynaptic release sites (N) are initially unoccupied by SVs, with vesicle recruitment occurring rapidly during activity, and furthermore that the number of release sites itself changes with rapid dynamics during activity. Here we propose a framework that identifies specific signs of the presence of the series-connected RP, using a combination of two experimental electrophysiological standard methods, cumulative analysis (CumAna) and multiple probability fluctuation analysis (MPFA). In particular we show that if the y-intercept (y(0)) of CumAna is larger than N reported by MPFA (y(0) > NMPFA) this is a strong indication for a series-connected RP. This is due to the fact that y(0) reports the sum of RRP and RP. Our analysis further suggests that this result is not affected by unoccupied release sites, as such empty sites contribute to both estimates, y(0) and NMPFA. We discuss experimental findings and models in the recent literature in the light of our theoretical considerations.

neuroscience↗

bioRxiv2024

Soil bacterial neutral lipid fatty acids: Markers for carbon storage or necromass?

Carbon storage is a common strategy of soil microbes to cope with resource fluctuations. Fungi use neutral lipids (triacylglycerols, TAGs) for storage, which can be quantified via their derived fatty acids (NLFAs). NLFAs specific to bacteria can also be abundant in soils, but are rarely analysed as soil bacteria are assumed to not store TAGs. Instead, bacterial NLFAs are thought to derive from degraded phospholipids (diacylglycerols, DAGs), and thus indicate bacterial necromass, but this interpretation lacks evidence. In this perspective, we synthesise knowledge from the literature and our own experimental results on the origin of soil bacterial NLFAs. In sum, we provide evidence that bacterial NLFAs are predominantly derived from TAGs used for carbon storage: (1) Several pure culture studies provide evidence for TAG production in selected bacterial isolates. (2) Screening of genomes showed that wax ester synthase/diacylglycerol acyltransferases, which mediate the last step of TAG synthesis, are abundant in bacterial isolates from soil, suggesting a widespread genetic capability to produce TAGs. (3) We experimentally created conditions of excess labile carbon by adding isotopically labelled glucose to soil. Glucose-13C was rapidly allocated into bacterial NLFAs, with higher relative enrichment than phospholipid-derived fatty acids, indicating storage. (4) DAGs are not necessarily produced--and may only be intermediate compounds--during phospholipid degradation. We conclude that soil bacterial NLFAs are mainly derived from storage compounds, but a potential contribution from degraded phospholipids needs further validation. Isotopic labelling could resolve this, making NLFAs a valuable biomarker for microbial storage compounds in soil. HighlightsO_LIBacterial NLFAs originate from triacylglycerols (TAGs) or degraded phospholipids C_LIO_LINeutral lipids are not necessarily produced during phospholipid degradation C_LIO_LISoil bacteria have the genetic potential to produce TAGs for storage C_LIO_LIRapid transfer of excess glucose-13C into soil bacterial NLFAs suggests storage C_LIO_LIBacterial NLFAs are markers for carbon storage rather than necromass C_LI

microbiology↗

bioRxiv2024

Strong family- and guild-specific responses of arbuscular mycorrhizal fungi to long-term deficiencies and imbalances of N, P and K

O_LIMany agroecosystems face nitrogen (N), phosphorus (P) or potassium (K) deficiencies due to imbalanced or insufficient nutrient replenishment after plant biomass harvest. How this affects the symbiosis between plants and arbuscular mycorrhizal fungi (AMF), and the abundance of exploration-based AMF guilds (i.e., rhizophilic, edaphophilic, ancestral) remains largely unknown. C_LIO_LIWe studied a 70-year nutrient-deficiency experiment in a managed grassland in central Austria, where aboveground biomass was harvested three times annually. N, P and K were fully, partially, or not replenished, causing long-term nutrient deficiencies and imbalances. We analysed AMF communities in soil and roots by DNA/RNA amplicon sequencing and fatty-acid biomarkers, alongside soil and plant community properties. C_LIO_LISoil AMF communities were affected by N and P deficiencies, while root AMF communities were most susceptible to K deficiency, showing a 50% biomass reduction. We observed distinct guild- and family-specific responses: The edaphophilic guild declined with N deficiency, while the rhizophilic guild decreased with P and K deficiencies. Families within each guild, particularly in the ancestral guild, showed differential responses, indicating complementary nutrient specializations at the family level. C_LIO_LIOur findings underscore the previously unrecognized role of K deficiency in AMF symbiosis and suggest the existence of nutrient-related functional subgroups within exploration-based AMF guilds. C_LI

ecology↗

bioRxiv2024

Inferring cell differentiation maps from lineage tracing data

During development, mulitpotent cells differentiate through a hierarchy of increasingly restricted progenitor cell types until they realize specialized cell types. A cell differentiation map describes this hierarchy, and inferring these maps is an active area of research spanning traditional single marker lineage studies to data-driven trajectory inference methods on single-cell RNA-seq data. Recent high-throughput lineage tracing technologies profile lineages and cell types at scale, but current methods to infer cell differentiation maps from these data rely on simple models with restrictive assumptions about the developmental process. We introduce a mathematical framework for cell differentiation maps based on the concept of potency, and develop an algorithm, Carta, that infers an optimal cell differentiation map from single-cell lineage tracing data. The key insight in Carta is to balance the trade-off between the complexity of the cell differentiation map and the number of unobserved cell type transitions on the lineage tree. We show that Carta more accurately infers cell differentiation maps on both simulated and real data compared to existing methods. In models of mammalian trunk development and mouse hematopoiesis, Carta identifies important features of development that are not revealed by other methods including convergent differentiation of specialized cell types, progenitor differentiation dynamics, and the refinement of routes of differentiation via new intermediate progenitors. Code availabilityCarta software is available at https://github.com/raphael-group/CARTA

bioinformatics↗

bioRxiv2024

Substantial hierarchical reductions of genetic and morphological traits in the evolution of rotiferan parasites

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/605096v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@469ecborg.highwire.dtl.DTLVardef@6330f4org.highwire.dtl.DTLVardef@22faf6org.highwire.dtl.DTLVardef@8a6704_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG During the last 800 million years of evolution animals radiated into a vast range of diversity of species and disparity of forms and lifestyles. The process involved a near hierarchical increase in complexity from life forms with few cell types to organisms with many hundreds of cell-types. However, neither genome size nor number of protein-coding genes can explain these differences and their biological basis remains elusive. Yet, recent studies have suggested that the evolution of complexity is closely linked to the acquisition of a class of protein coding gene-regulators called microRNAs. In a regressive approach, to investigate the association between loss of organismal complexity and microRNAs, we here studied Syndermata, an invertebrate group including free-living rotifers (Monogononta, Bdelloidea), the epibiotic Seisonidea and the endoparasitic Acanthocephala. Genomic, transcriptomic and morphological characterization and comparisons across 25 syndermatan species revealed a strong correlation between loss of microRNAs, loss of protein-coding genes and decreasing morphological complexity. The near hierarchical loss extends to [~]85% loss of microRNAs and a [~]50% loss of BUSCO genes in the endoparasitic Acanthocephala, the most reduced group we studied. Together, the loss of [~]400 protein-coding genes and [~]10 metazoan core gene losses went along with one microRNA family loss. Furthermore, the loss of [~]4 microRNA families or [~]34 metazoan core genes associated with one lost morphological feature. These are the first quantitative insights into the regulatory impact of microRNAs on organismic complexity as a predictable consequence in regressive evolution of parasites.

evolutionary biology↗

bioRxiv2024

Distinct microbial communities are linked to organic matter properties in millimetre-sized soil aggregates

Soils provide essential ecosystem services and represent the most diverse habitat on Earth. It has been suggested that the presence of various physico-chemically heterogenous microhabitats supports the enormous diversity of microbial communities in soil. However, little is known about the relationship between microbial communities and their immediate environment at the micro- to millimetre-scale. In this study, we examined whether bacteria, archaea, and fungi organise into distinct communities in individual 2-millimetre-sized soil aggregates and compared them to communities of homogenized bulk soil samples. Furthermore, we investigated their relationship to their local environment by concomitantly determining microbial community structure and physico-chemical properties from the same individual aggregates. Aggregate-communities displayed exceptionally high beta-diversity, with 3-4 aggregates collectively capturing more diversity than their homogenized parent soil core. Up to 20-30% of ASVs (particularly rare ones) were unique to individual aggregates selected within a few centimetres. Aggregates and bulk soil samples showed partly different dominant phyla, indicating that taxa that are potentially driving biogeochemical processes at the small scale may not be recognized when analysing larger soil volumes. Microbial community composition and richness of individual aggregates were closely related to aggregate-specific carbon and nitrogen content, carbon stable-isotope composition, and soil moisture, indicating that aggregates provide a stable environment for sufficient time to allow co-development of communities and their environment. We conclude that the soil microbiome is a metacommunity of variable subcommunities. Our study highlights the necessity to study small, spatially coherent soil samples to better understand controls of community structure and community-mediated processes in soils.

ecology↗

bioRxiv2024

Neuronal Hyperactivity in Neurons Derived from Individuals with Grey Matter Heterotopia

Periventricular heterotopia (PH), a common form of grey matter heterotopia associated with developmental delay and drug-resistant seizures, poses a challenge in understanding its neurophysiological basis. Human cerebral organoids (hCOs) derived from patients with causative mutations in FAT4 or DCHS1 mimic PH features. However, neuronal activity in these 3D models has not yet been invetigated. Here, silicon probe recordings revealed exaggerated spontaneous spike activity in FAT4 and DCHS1 hCOs, suggesting functional changes in neuronal networks. Transcriptome and proteome analyses identified changes in gene ontology terms associated with neuronal morphology and synaptic function. Furthermore, patch-clamp recordings revealed a decreased spike threshold specifically in DCHS1 neurons, likely due to increased somatic voltage-gated sodium channels. Morphological reconstructions and immunostainings revealed greater morphological complexity of PH neurons and synaptic alterations contributing to hyperactivity, with morphological rescue observed in DCHS1 neurons by wild-type DCHS1 expression. Overall, we provide new comprehensive insights into the cellular changes underlying symptoms of grey matter heterotopia.

neuroscience↗

bioRxiv2024

The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell division in vivo

The mechanisms that enable differential gene expression in daughter cells produced by asymmetric cell divisions are not well understood. We discovered that the eukaryotic replicative helicase CMG (Cdc45-MCM-GINS) is required for this process in C. elegans. During C. elegans development, some dividing cells give rise to a daughter that survives and a daughter that dies. We found that PSF-2 GINS2, a component of C. elegans CMG, is necessary for the transcriptional burst of the pro-apoptotic gene egl-1 BH3-only, which occurs in the daughter that dies immediately following mother cell division. We present evidence that this requirement is independent of the function of CMG in DNA unwinding. We propose that the recently described histone chaperone activity of CMG causes epigenetic changes at the egl-1 locus during replication in mother cells, and that these changes are required for the increase in egl-1 transcription in the daughter that dies. We also find that PSF-2 is required for the divergence of other cell fates during C. elegans development, suggesting that this function is not restricted to the regulation of egl-1 expression. Our work uncovers a new and unexpected role of CMG in cell fate and a novel intrinsic mechanism for gene expression plasticity in the context of asymmetric cell division.

cell biology↗

bioRxiv2024

A regression based approach to phylogenetic reconstruction from multi-sample bulk DNA sequencing of tumors

MotivationDNA sequencing of multiple bulk samples from a tumor provides the opportunity to investigate tumor heterogeneity and reconstruct a phylogeny of a patients cancer. However, since bulk DNA sequencing of tumor tissue measures thousands of cells from a heterogeneous mixture of distinct sub-populations, accurate reconstruction of the tumor phylogeny requires simultaneous deconvolution of cancer clones and inference of ancestral relationships, leading to a challenging computational problem. Many existing methods for phylogenetic reconstruction from bulk sequencing data do not scale to large datasets, such as recent datasets containing upwards of ninety samples with dozens of distinct sub-populations. ResultsWe develop an approach to reconstruct phylogenetic trees from multi-sample bulk DNA sequencing data by separating the reconstruction problem into two parts: a structured regression problem for a fixed tree [T], and an optimization over tree space. We derive an algorithm for the regression sub-problem by exploiting the unique, combinatorial structure of the matrices appearing within the problem. This algorithm has both asymptotic and empirical improvements over linear programming (LP) approaches to the problem. Using our algorithm for this regression sub-problem, we develop fastBE, a simple method for phylogenetic inference from multi-sample bulk DNA sequencing data. We demonstrate on simulated data with hundreds of samples and upwards of a thousand distinct sub-populations that fastBE outperforms existing approaches in terms of reconstruction accuracy, sample efficiency, and runtime. Owing to its scalability, fastBE also enables phylogenetic reconstruction directly from indvidual mutations without requiring the clustering of mutations into clones. On real data from fourteen B-progenitor acute lymphoblastic leukemia patients, fastBE infers similar phylogenies to the existing, state-of-the-art method, but with fewer violations of a widely used evolutionary constraint and better agreement to the observed mutational frequencies. Finally, we show that on two patient-derived colorectal cancer models, fastBE also infers phylogenies with less violation of a widely used evolutionary constraint compared to existing methods, and leads to distinct interpretations of the intra-tumor heterogeneity. AvailabilityfastBE is implemented in C++ and is available at: github.com/raphael-group/fastBE.

cancer biology↗

bioRxiv2024

Unexpectedly dense colonization of soil pore space by microbes

Pore surfaces in soil are considered to be sparsely colonised, dispersed only with isolated cells or colonies of bacteria and archaea. Here, we question this empty space-concept by combining microstructure analysis with molecular biology and provide a data-driven update on habitable surface areas (HSA) in soil. Our unique approach allowed us to provide 1) evidence that microbial densities in soil have been underestimated for decades and 2) two-dimensional simulations of their potential distribution within the soil pore space. Our results demonstrate the need for a new perspective on how densely soil is colonised, with implications for how we think of basic ecological processes such as microbial motility or predation, and how microbial processes, including organic matter dynamics, are ultimately modelled.

ecology↗

bioRxiv2024

Brain-wide monosynaptic connectivity mapping with ROInet-seq

Viral projection tracing strategies help establish regional connectomes of mammalian brains. Monosynaptic connectivity tracing with G-deleted rabies virus (RV) establishes synaptic input connectivity, but cannot distinguish networks at cell resolution. We implemented a barcoded {Delta}G rabies virus to introduce unique molecular tags - and make network tracing amenable to readout by RNA-sequencing. First, we optimized and characterized library complexity and uniformity, such that detection of specific barcodes can reliably distinguish the individual monosynaptic input networks of multiple infected neurons in parallel. To deploy the method at scale; to hundreds of cells and full-brain volume per experiment, we developed regions-of-interest network sequencing (ROInet-seq); an accessible, scalable and low-cost spatial assay. ROInet-seq combines routine fluorescent imaging and processing of fixed tissue sections with a simple molecular biology workflow to capture barcode sequences in relevant regions-of-interest, and ultimately describes single-neuron networks brain-wide. In cortical brain areas the assay revealed preserved regional network motives, including co-inputs to single cortical neurons from distant and local sites. Towards improved spatial resolution and simultaneous detection of transcriptomes and networks we finally sampled barcoded {Delta}G rabies virus-infected hippocampus on commercial spatial transcriptomics assays and reveal details of the regions neurons local network architecture.

neuroscience↗

bioRxiv2024

The intracellular Ca2+ sensitivity of transmitter release from neocortical boutons

Synaptotagmin 1 (Syt1) and Syt2 are the main Ca2+ sensors triggering synchronous release in the brain. The Ca2+-sensitivity of Syt2-triggered release has been studied in detail. However, for Syt1, the dominating isoform in the neocortex, quantitative detail is lacking. We measured the Ca2+-dependency of Syt1-triggered release at layer 5 pyramidal neuron synapses by laser photolysis of caged Ca2+. Syt1-triggered release had high Ca2+ affinity and positive cooperativity (EC50, 20 M; Hill coefficient, 3.57). It was steep in a dynamic range between [~]10 and [~]30 M that was covered by action potential-evoked release. A kinetic model reveals significant differences to models of Syt2-triggered release. Our results suggest that Syt1 optimizes neocortical synapses for high reliability at moderate local Ca2+ elevations and for high plastic controllability.

neuroscience↗

bioRxiv2024

Age-Related Dynamics of Methanogenic Archaea in the Human Gut Microbiome: Implications for Longevity and Health

The reciprocal relationship between aging and alterations in the gut microbiota is a subject of ongoing research. While the role of bacteria in the gut microbiome is well-documented, specific changes in the composition of methanogens during extreme aging and the impact of high methane production in general on health remain unclear. To address these questions, we analyzed metagenomic data from the stool samples of young adults (n=127, Age: 19-59 y), older adults (n=86), and centenarians (n=34, age: 100-109 years). Our findings reveal a compelling link between age and the prevalence of high methanogen phenotype, while overall archaeal diversity diminishes. Surprisingly, the archaeal composition of methanogens in the microbiome of centenarians appears more akin to that of younger adults, showing an increase in Methanobrevibacter smithii, rather than Ca. M. intestini. Remarkably, Ca. M. intestini emerged as a central player in the network stability of adults, paving the way for M. smithii in older adults and centenarians. Notably, centenarians exhibit a highly complex and stable network of these two methanogens with other bacteria. Furthermore, the mutual exclusion between Lachnospiraceae and these methanogens throughout all age groups suggests that these archaeal communities may compensate for the age-related drop in Lachnospiraceae by co-occurring with butyrate-producing Oscillospiraceae. This study underscores the crucial role of the archaeal microbiome in human physiology and aging. It highlights age-related shifts in methanogen composition, emphasizing the significance of Ca. M. intestini and the partnership between methanogens and specific butyrate-producing bacteria for enhanced health and potential longevity.

microbiology↗

bioRxiv2023

Molecular determinants of SEC61A1 mutant R236C in two patient-derived cellular platforms

Background & objectivesSEC61A1 encodes a central protein of the mammalian translocon machinery residing in the ER. Mutations of SEC61A1 are implicated to result in various severe diseases. Recently, mutation R236C was identified in patients having autosomal dominant polycystic liver disease (ADPLD), which originates from defects of cholangiocytes in the liver. The molecular phenotype of R236C was assessed. MethodsTwo cellular platforms were established from the same cell source of an ADPLD patient by different methodology. Cells were immortalized by retroviral transduction of an oncogene (UCi) or reprogrammed to induced pluripotent stem cells (iPSC) that were differentiated to cholangiocyte progenitor-like cells (CPLC). UCi and CPLC were subjected to several analyses of molecular pathways that were previously associated with development of polycystic disease. ResultsUCi displayed markers of epithelial cells, while CPLCs expressed typical markers of both cholangiocytes and hepatocytes. Cells encoding R236C showed a stable, continuous proliferation in both platforms, however growth rates were reduced as compared to wildtype control. Autophagy, cAMP synthesis, and secretion of important marker proteins were reduced in R236C-expressing cells. In addition, R236C induced increased calcium leakiness from the ER to the cytoplasm. Upon oxidative stress, R236C led to a high induction of apoptosis and necrosis. ConclusionAlthough the grade of aberrant cellular functions differed between the two platforms, overall the molecular phenotype of R236C was shared suggesting that the mutation, regardless of the cell type, has a dominant impact on disease-associated pathways that cause ADPLD. Our approach may be valuable to decipher the molecular pathways of other rare genetic diseases using patient-specific cell models.

cell biology↗

bioRxiv2023

Bacteria face trade-offs in the decomposition of complex biopolymers

Although depolymerization of complex carbohydrates is a growth-limiting bottleneck for microbial decomposers, we still lack understanding about how the production of different types of extracellular enzymes affect individual microbes and in turn the performance of whole decomposer communities. In this work we use a theoretical model to evaluate the potential trade-offs faced by microorganisms in biopolymer decomposition which arise due to the varied biochemistry of different depolymerizing enzyme classes. We specifically consider two broad classes of depolymerizing extracellular enzymes, which are widespread across microbial taxa: exo-enzymes that cleave small units from the ends of polymer chains and endo-enzymes that act at random positions generating degradation products of varied sizes. Our results demonstrate a fundamental trade-off in the production of these enzymes, which is independent of systems complexity and which appears solely from the intrinsically different temporal depolymerization dynamics. As a consequence, specialists that produce either exo- or only endo-enzymes limit their growth to high or low substrate conditions, respectively. Conversely, generalists that produce both enzymes in an optimal ratio expand their niche and benefit from the synergy between the two enzymes. Finally, our results show that, in spatially-explicit environments, consortia composed of endo- and exo-specialists can only exist under oligotrophic conditions. In summary, our analysis demonstrates that the (evolutionary or ecological) selection of a depolymerization pathway will affect microbial fitness under low- or high substrate conditions, with impacts on the ecological dynamics of microbial communities. It provides a possible explanation why many polysaccharide degraders in nature show the genetic potential to produce both of these enzyme classes. Author summaryThe decomposition of polysaccharides by microbes is a key process in the global carbon cycle. It requires the joint action of a variety of microbially-produced extracellular enzymes. They can be broadly classified into endo-enzymes, that act in the middle of polymers, and exo-enzymes, that cleave units from polymer ends. Little is known about the benefits for microbes producing a certain enzyme type and the interplay between enzyme producing strategies in mixed communities. This hampers our comprehensive understanding of decomposition in terrestrial and marine ecosystems and thus limits the prediction of decomposition processes, for example in a changing climate. Based on theoretical modelling, we revealed a fundamental trade-off in the action of these enzymes. While exo-enzymes are more efficient at high substrate conditions, endo-enzymes perform better when substrate is low. Generalists producing both enzymes expand their ecological niche of substrate availability compared to specialists only producing one of the two types. Complementary specialists only co-exist in oligotrophic conditions. We conclude that producing enzymes for specific steps within polymer degradation represents relevant ecological strategies for microbes in decomposer communities.

microbiology↗

bioRxiv2023

Open-loop lab-on-a-chip technology enables remote computer science training in Latinx life sciences students

Despite many interventions, science education remains highly inequitable throughout the world. Among all life sciences fields, Bioinformatics and Computational Biology suffer from the strongest underrepresentation of racial and gender minorities. Internet-enabled project-based learning (PBL) has the potential to reach underserved communities and increase the diversity of the scientific workforce. Here, we demonstrate the use of lab-on-a-chip (LoC) technologies to train Latinx life science undergraduate students in concepts of computer programming by taking advantage of open-loop cloud-integrated LoCs. We developed a context-aware curriculum to train students at over 8,000 km from the experimental site. We showed that this approach was sufficient to develop programming skills and increase the interest of students in continuing careers in Bioinformatics. Altogether, we conclude that LoC-based Internet-enabled PBL can become a powerful tool to train Latinx students and increase the diversity in STEM.

scientific communication and education↗