Biology subjects

Miller, A. K.

Publications and source records attributed to Miller, A. K..

At least 19 recordsLinked to original sources

bioRxiv2026

PHC2-Dependent PRC1 Assemblies Stabilize Motor Neuron Hox Codes

Polycomb Repressive Complexes PRC1 and PRC2 establish and maintain chromatin architectures critical for cell-type specific gene expression. In the developing spinal cord, PRC1 is essential for implementing Hox-dependent transcriptional programs that diversify motor neuron identities. Although PRC1 can assemble into subnuclear condensates, whether these structures contribute to the specification and maintenance of neuronal subtype fates remains unclear. Using chick and mouse models, we show that canonical PRC1 components - BMI1, PHC2, CBX2, RING1B - coalesce into subnuclear assemblies as neural progenitors differentiate into motor neurons. Disrupting PHC2 polymerization in either neural progenitors or postmitotic neurons dismantles BMI1-containing PRC1 assemblies, triggering derepression of caudal Hox genes and a cell autonomous loss of segment-specific motor neuron fates. Mouse mutants lacking the core PRC1 subunit Ring1 fail to form BMI1-containing assemblies, despite intact PHC2 and CBX2 polymers. In contrast, motor neuron-restricted deletion of core PRC2 subunits (Ezh1/2) depletes H3K27me3 histone marks but retains PRC1 assemblies and Hox boundaries. Together, these findings indicate that PHC2-dependent PRC1 assemblies stabilize Hox transcriptional boundaries and motor neuron segmental identities.

developmental biology↗

bioRxiv2026

Rational scaffold design mitigates mitochondrial complex I off-target inhibition in bifunctional degraders

Chemical inducers of proximity have transformed small-molecule pharmacology, but the large, bifunctional architectures they often employ introduce new and poorly understood off-target risks. During a targeted protein degrader synthesis project, we identified a subset of compounds that cause rapid and unexpected ATP depletion in cells. Mechanistic studies traced this effect to inhibition of mitochondrial complex I, a central component of oxidative phosphorylation. This inhibition does not stem from off-target binding by either of the two target ligands, but from the overall long, linear architecture of the bifunctional molecules, which renders them effective ligands of the narrow ubiquinone binding tunnel of complex I. Strikingly, this liability extends to structurally unrelated bifunctional molecules, including six androgen receptor PROTACs including the clinical candidate ARV-110, which inhibits complex I at low nanomolar concentrations. To mitigate complex I inhibition, we established a generalizable design strategy to disrupt linear molecular geometry through the introduction of structural "bumps" or "kinks". In a proof-of-concept study, we successfully apply this strategy to the ARV-110 scaffold, discovering potent AR-degrading ARV-110 analogs that do not inhibit complex I. These findings uncover a previously underappreciated structural determinant of off-target mitochondrial toxicity and establish new design principles for safer proximity-inducing therapeutics.

cancer biology↗

bioRxiv2025

Foraging ecology drives viral community structure in New Zealand's aquatic birds

Wild migratory birds play a major role in the global spread of viruses, yet the diversity, host range and transmission patterns of viruses harboured by migratory species in Aotearoa/New Zealand remain largely unknown. This knowledge gap is critical given New Zealands position along major migratory flyways spanning Oceania, Antarctica and east Asia, where understanding viral diversity is key to assessing the risk of viral introductions such as highly pathogenic avian influenza virus and viral dispersal across these regions. To address this, we conducted the first large-scale metatranscriptomic survey of wild birds from New Zealand and its subantarctic islands, collecting 1,348 samples from 31 host species spanning four avian orders. We identified 118 avian viruses from 17 families, including 107 novel species, greatly expanding our knowledge of avian viral diversity. Viral communities differed significantly by host order and foraging behaviour, with scavenger birds harbouring more diverse viromes than non-scavengers. Although no HPAI subtypes were detected, we recovered a low-pathogenic avian influenza A/H1N9 virus from red knots (Calidris canutus) and a divergent tobanivirus from Auckland Island teal (Anas aucklandica), the first putative avian member of the Tobaniviridae. Notably, we detected 12 mammalian-associated viruses, primarily in scavenger birds, including Hedgehog hepatovirus, Rabbit haemorrhagic disease virus 2, and sea lion astroviruses, with mammalian host reads confirming their dietary origin. This study establishes the first virome baseline for New Zealands migratory birds, highlighting the ecological role of foraging in shaping viral communities and improving regional preparedness for HPAI and other emerging avian pathogens.

microbiology↗

bioRxiv2025

Evaluating sampling strategies for the detection of avian influenza viruses in the environment

Highly pathogenic avian influenza (HPAI) viruses threaten humans, livestock and wildlife, highlighting the urgent need for early warning surveillance. Environmental RNA (eRNA) monitoring provides a safer, cost-effective and non-invasive alternative to direct pathogen testing, yet the effectiveness of different sample types for avian influenza viruses (AIVs) is unclear. We evaluated four eRNA-based sampling methods in urban waterfowl ponds over approximately one year. All methods combined with RT-qPCR and metagenomic sequencing detected AIV, but detections were asynchronous, likely reflecting low viral concentrations or detection limits. These results highlight both the promise and the current limitations of eRNA-based AIV surveillance. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/677014v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@e8e189org.highwire.dtl.DTLVardef@12f17fforg.highwire.dtl.DTLVardef@d09f5forg.highwire.dtl.DTLVardef@8f55fd_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

An Anaerobic Pathogen Rewires Host Metabolism to Fuel Oxidative Growth in the Inflamed Gut

To colonize their host and cause disease, enteric pathogens must deploy their virulence factors to establish distinct nutrient niches. How obligate anaerobic pathogens construct nutrient niches in the densely populated large intestine remains poorly understood. Enterotoxigenic Bacteroides fragilis (ETBF) is considered an obligate anaerobic bacterium and has been implicated in inflammation-associated diseases, including colitis and colorectal cancer. Here we show that ETBF uses its virulence factor, Bacteroides fragilis toxin, to reprogram colonic epithelial cell metabolism to colonize the inflamed gut. Bacteroides fragilis toxin activates colonic epithelial signaling and hijacks the host bile acid recycling pathway, inducing a metabolic shift in the epithelium from oxidative phosphorylation to glycolysis. This shift increases local concentrations of lactate and oxygen, nutrients that support an oxidative metabolism in ETBF. These findings reveal an unexpected strategy by which a pathogenic organism, previously considered to be an obligate anaerobic bacterium, generates and exploits an oxidative niche in the inflamed gut.

microbiology↗

bioRxiv2024

tombRaider - improved species and haplotype recovery from metabarcoding data through artefact and pseudogene exclusion.

Environmental DNA metabarcoding has revolutionized ecological surveys of natural systems. By amplifying and sequencing small gene fragments from environmental samples containing complex DNA mixtures, scientists are now capable of exploring biodiversity patterns across the tree of life in a time-efficient and cost-effective manner. However, the accuracy of species and haplotype identification can be compromised by sequence artefacts and pseudogenes. Despite various strategies developed over the years, effective removal of artefacts remains challenging and inconsistent data reporting standards hinder reproducibility in eDNA metabarcoding experiments. To address these issues, we introduce tombRaider, an open-source command line software program (https://github.com/gjeunen/tombRaider) and R package (https://github.com/gjeunen/tombRaider_R) to remove artefacts and pseudogenes from metabarcoding data post clustering and denoising. tombRaider features a modular algorithm capable of evaluating multiple criteria, including sequence similarity, co-occurrence patterns, taxonomic assignment, and the presence of stop codons. We validated tombRaider using various published data sets, including mock invertebrate communities, air eDNA from a zoo, and salmon haplotypes from aquatic eDNA. Our results demonstrate that tombRaider effectively removed a higher proportion of artefacts while retaining authentic sequences, thus enhancing the accuracy and reliability of eDNA-derived diversity metrics. This user-friendly software program not only improves data quality in eDNA metabarcoding studies, but also contributes to standardised reporting practices, an aspect currently lacking in this emerging research field.

bioinformatics↗

bioRxiv2023

Paracrine enhancement of tumor cell proliferation provides indirect stroma-mediated chemoresistance via acceleration of tumor recovery between chemotherapy cycles.

The ability of tumors to survive therapy reflects both cell-intrinsic and microenvironmental mechanisms. Across many cancers, including triple-negative breast cancer (TNBC), a high stroma/tumor ratio correlates with poor survival. In many contexts, this correlation can be explained by the direct reduction of therapy sensitivity by stroma-produced paracrine factors. We sought to explore whether this direct effect contributes to the link between stroma and poor responses to chemotherapies. Our in vitro studies with panels of TNBC cell line models and stromal isolates failed to detect a direct modulation of chemoresistance. At the same time, consistent with prior studies, we observed treatment-independent enhancement of tumor cell proliferation by fibroblast-produced secreted factors. Using spatial statistics analyses, we found that proximity to stroma is often associated with enhanced tumor cell proliferation in vivo. Based on these observations, we hypothesized an indirect link between stroma and chemoresistance, where stroma-augmented proliferation potentiates the recovery of residual tumors between chemotherapy cycles. To evaluate the feasibility of this hypothesis, we developed a spatial agent-based model of stroma impact on proliferation/death dynamics. The model was quantitatively parameterized using inferences from histological analyses and experimental studies. We found that the observed enhancement of tumor cell proliferation within stroma-proximal niches can enable tumors to avoid elimination over multiple chemotherapy cycles. Therefore, our study supports the existence of a novel, indirect mechanism of environment-mediated chemoresistance that might contribute to the negative correlation between stromal content and poor therapy outcomes.

cancer biology↗

bioRxiv2023

Low level of antioxidant capacity biomarkers but not target overexpression predicts vulnerability to ROS-inducing drugs

Despite a strong rationale for why cancer cells are susceptible to redox-targeting drugs, such drugs often face tumor resistance or dose-limiting toxicity in preclinical and clinical studies. An important reason is the lack of specific biomarkers to better select susceptible cancer entities and stratify patients. Using a large panel of lung cancer cell lines, we identified a set of "antioxidant-capacity" biomarkers (ACB), which were tightly repressed, partly by STAT3 and STAT5A/B in sensitive cells, rendering them susceptible to multiple redox-targeting and ferroptosis-inducing drugs. Contrary to expectation, constitutively low ACB expression was not associated with an increased steady state level of reactive oxygen species (ROS) but a high level of nitric oxide, which is required to sustain high replication rates. Using ACBs, we identified cancer entities with a high percentage of patients with favorable ACB expression pattern, making it likely that more responders to ROS-inducing drugs could be stratified for clinical trials.

cancer biology↗

bioRxiv2022

Confusion will be my epitaph: Genome-scale discordance stifles phylogenetic resolution of Holothuroidea

Sea cucumbers (Holothuroidea) are a diverse clade of echinoderms found from intertidal waters to the bottom of the deepest trenches. Their reduced skeletons and limited number of phylogenetically-informative traits have long obfuscated morphological classifications. Sanger-sequenced molecular datasets have also failed to constrain the position of major lineages. Noteworthy, topological uncertainty has hindered a resolution for Neoholothuriida, a highly diverse clade of Permo-Triassic age. We perform the first phylogenomic analysis of Holothuroidea, combining existing datasets with twelve novel transcriptomes. Using a highly-curated dataset of 1,100 orthologues, our efforts recapitulate previous results, struggling to resolve interrelationships among neoholothuriid clades. Three approaches to phylogenetic reconstruction (concatenation under both site-homogeneous and site-heterogeneous models, and coalescent-aware inference) result in alternative resolutions, all of which are recovered with strong support, and across a range of datasets filtered for phylogenetic usefulness. We explore this intriguing result using gene-wise log-likelihood scores, and attempt to correlate these with a large set of gene properties. While presenting novel ways of exploring and visualizing support for alternative trees, we are unable to discover significant predictors of topological preference, and our efforts fail to favor one topology. Neoholothuriid genomes seem to retain an amalgam of signals derived from multiple phylogenetic histories.

evolutionary biology↗

bioRxiv2022

Non-invasive real-time genomic monitoring of the critically endangered kakapo

We used non-invasive real-time genomic approaches to monitor one of the last surviving populations of the critically endangered k[a]k[a]p[o] (Strigops habroptilus). We first established an environmental DNA metabarcoding protocol to identify the distribution of k[a]k[a]p[o] and other vertebrate species in a highly localized manner using soil samples. Harnessing real-time nanopore sequencing and the high-quality k[a]k[a]p[o] reference genome, we then extracted species-specific DNA from soil. We combined long read-based haplotype phasing with known individual genomic variation in the k[a]k[a]p[o] population to identify the presence of individuals, and confirmed these genomically informed predictions through detailed metadata on k[a]k[a]p[o] distributions. This study shows that individual identification is feasible through nanopore sequencing of environmental DNA, with important implications for future efforts in the application of genomics to the conservation of rare species, potentially expanding the application of real-time environmental DNA research from monitoring species distribution to inferring fitness parameters such as genomic diversity and inbreeding.

genomics↗

bioRxiv2022

The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous proteasome inhibitor resistant disease

Multiple myeloma (MM) is an osteolytic plasma cell malignancy that, despite being responsive to therapies such as proteasome inhibitors, frequently relapses. Understanding the mechanism and the niches where resistant disease evolves remains of major clinical importance. Cancer cell intrinsic mechanisms and bone ecosystem factors are known contributors to the evolution of resistant MM but the exact contribution of each is difficult to define with current in vitro and in vivo models. However, mathematical modeling can help address this gap in knowledge. Here, we describe a novel biology-driven hybrid agent-based model that incorporates key cellular species of the bone ecosystem that control normal bone remodeling and, in MM, yields a protective environment under therapy. Critically, the spatiotemporal nature of the model captures two key features: normal bone homeostasis and how MM interacts with the bone ecosystem to induce bone destruction. We next used the model to examine how the bone ecosystem contributes to the evolutionary dynamics of resistant MM under control and proteasome inhibitor treatment. Our data demonstrates that resistant disease cannot develop without MM intrinsic mechanisms. However, protection from the bone microenvironment dramatically increases the likelihood of developing intrinsic resistance and subsequent relapse. The spatial nature of the model also reveals how the bone ecosystem provides a protective niche for drug sensitive MM cells under treatment, consequently leading to the emergence of a heterogenous and drug resistant disease. In conclusion, our data demonstrates a significant role for the bone ecosystem in MM survival and resistance, and suggests that early intervention with bone ecosystem targeting therapies may prevent the emergence of heterogeneous drug resistant MM.

cancer biology↗

bioRxiv2022

Omnigenic epistasis regulates complex trait heritability

A better understanding of genetic architecture will help translate genetic data into improved precision-based medicine and clinical care. Towards this end, we explored the use of sex-stratified analyses for several traits in the Hybrid Mouse Diversity Panel (HMDP) and UK Biobank to better determine trait polygenicity and identify contributing loci. This was accomplished by comparing the direction of allelic effects in males and females in sex-stratified analyses under the hypothesis that loci that are not associated with a trait should have equal chances of trending in the same direction of effect. Instead, we found that even for most alleles that do not meet nominal levels of statistical significance, the direction of effect in the two sexes was highly concordant. Results were consistent with hundreds of loci regulating each mouse trait and thousands of loci regulating each human trait, including traits for which no statistically significant loci were identified using conventional approaches. We also found evidence of likely spurious widespread epistasis. Collectively, these findings demonstrate the importance of stratifying by sex to discover novel associating loci, suggest a new method for identifying biologically rather than statistically significant associations, and caution that widespread marginal effects can lead to phantom epistasis.

genetics↗

bioRxiv2022

RefZ and Noc act synthetically to prevent aberrant divisions during Bacillus subtilis sporulation

During sporulation, Bacillus subtilis undergoes an atypical cell division that requires overriding mechanisms which protect chromosomes from damage and ensure inheritance by daughter cells. Instead of assembling between segregated chromosomes at midcell, the FtsZ-ring (Z-ring) coalesces polarly, directing division over one chromosome. The DNA-binding protein RefZ facilitates the timely assembly of polar Z-rings and partially defines the region of chromosome initially captured in the forespore. RefZ binds to motifs (RBMs) located proximal to the origin of replication (oriC). Although refZ and the RBMs are conserved across the Bacillus genus, a refZ deletion mutant sporulates with wildtype efficiency, so the functional significance of RefZ during sporulation remains unclear. To further investigate RefZ function, we performed a candidate-based screen for synthetic sporulation defects by combining {Delta}refZ with deletions of genes previously implicated in FtsZ regulation and/or chromosome capture. Combining {Delta}refZ with deletions of ezrA, sepF, parA, or minD did not detectably affect sporulation. In contrast, a {Delta}refZ {Delta}noc mutant exhibited a sporulation defect, revealing a genetic interaction between RefZ and Noc. Using reporters of sporulation progression, we determined the {Delta}refZ {Delta}noc mutant exhibited sporulation delays after Spo0A activation but prior to late sporulation, with a subset of cells failing to divide polarly or activate the first forespore-specific sigma factor, SigF. The {Delta}refZ {Delta}noc mutant also exhibited extensive dysregulation of cell division, producing cells with extra, misplaced, or otherwise aberrant septa. Our results reveal a previously unknown epistatic relationship that suggests refZ and noc contribute synthetically to regulating cell division and supporting spore development. IMPORTANCEThe DNA-binding protein RefZ and its binding sites (RBMs) are conserved in sequence and location on the chromosome across the Bacillus genus and contribute to the timing of polar FtsZ-ring assembly during sporulation. Only a small number of non-coding and non-regulatory DNA motifs are known to be conserved in chromosomal position in bacteria, suggesting there is strong selective pressure for their maintenance; however a refZ deletion mutant sporulates efficiently, providing no clues as to their functional significance. Here we find that in the absence of the nucleoid occlusion factor Noc, deletion of refZ results in a sporulation defect characterized by developmental delays and aberrant divisions.

microbiology↗

bioRxiv2021

Slippery when wet: cross-species transmission of divergent coronaviruses in bony and jawless fish and the evolutionary history of the Coronaviridae

The Nidovirales comprise a genetically diverse group of positive-sense single-stranded RNA virus families that infect a range of invertebrate and vertebrate hosts. Recent metagenomic studies have identified nido-like virus sequences, particularly those related to the Coronaviridae, in a range of aquatic hosts including fish, amphibians and reptiles. We sought to identify additional members of the Coronaviridae in both bony and jawless fish through a combination of total RNA sequencing (meta-transcriptomics) and data mining of published RNA sequencing data, and from this reveal more of the long-term patterns and processes of coronavirus evolution. Accordingly, we identified a number of divergent viruses that fell within the Letovirinae subfamily of the Coronaviridae, including those in a jawless fish - the pouched lamprey. By mining fish transcriptome data we identified additional virus transcripts matching these viruses in bony fish from both marine and freshwater environments. These new viruses retained sequence conservation in the RNA-dependant RNA polymerase across the Coronaviridae, but formed a distinct and diverse phylogenetic group. Although there are broad-scale topological similarities between the phylogenies of the major groups of coronaviruses and their vertebrate hosts, the evolutionary relationships of viruses within the Letovirinae does not mirror that of their hosts. For example, the coronavirus found in the pouched lamprey fell within the phylogenetic diversity of bony fish letoviruses, indicative of past host switching events. Hence, despite possessing a phylogenetic history that likely spans the entire history of the vertebrates, coronavirus evolution has been characterised by relatively frequent cross-species transmission, particularly in hosts that reside in aquatic habitats.

microbiology↗

bioRxiv2021

Genomes of gut bacteria from Nasonia wasps shed light on phylosymbiosis and microbe-assisted hybrid breakdown

Phylosymbiosis is a cross-system trend whereby microbial community relationships recapitulate the host phylogeny. In Nasonia parasitoid wasps, phylosymbiosis occurs throughout development, is distinguishable between sexes, and benefits host development and survival. Moreover, the microbiome shifts in hybrids as a rare Proteus bacteria in the microbiome becomes dominant. The larval hybrids then catastrophically succumb to bacterial-assisted lethality and reproductive isolation between the species. Two important questions for understanding phylosymbiosis and bacterial-assisted lethality in hybrids are: (i) Do the Nasonia bacterial genomes differ from other animal isolates and (ii) Are the hybrid bacterial genomes the same as those in the parental species? Here we report the cultivation, whole genome sequencing, and comparative analyses of the most abundant gut bacteria in Nasonia larvae, Providencia rettgeri and Proteus mirabilis. Characterization of new isolates shows Proteus mirabilis forms a more robust biofilm than Providencia rettgeri and when grown in co-culture, Proteus mirabilis significantly outcompetes Providencia rettgeri. Providencia rettgeri genomes from Nasonia are similar to each other and more divergent to pathogenic, human-associates strains. Proteus mirabilis from N. vitripennis, N. giraulti, and their hybrid offspring are nearly identical and relatively distinct from human isolates. These results indicate that members of the larval gut microbiome within Nasonia are most similar to each other, and the strain of the dominant Proteus mirabilis in hybrids is resident in parental species. Holobiont interactions between shared, resident members of the wasp microbiome and the host underpin phylosymbiosis and hybrid breakdown. IMPORTANCEAnimal and plant hosts often establish intimate relationships with their microbiomes. In varied environments, closely-related host species share more similar microbiomes, a pattern termed phylosymbiosis. When phylosymbiosis is functionally significant and beneficial, microbial transplants between host species or host hybridization can have detrimental consequences on host biology. In the Nasonia parasitoid wasp genus that contains a phylosymbiotic gut community, both effects occur and provide evidence for selective pressures on the holobiont. Here, we show that bacterial genomes in Nasonia differ from other environments and harbor genes with unique functions that may regulate phylosymbiotic relationships. Furthermore, the bacteria in hybrids are identical to parental species, thus supporting a hologenomic tenet that the same members of the microbiome and the host genome impact phylosymbiosis, hybrid breakdown, and speciation.

microbiology↗

bioRxiv2020

Revealing heritability missed by single locus analyses by examining epistasis in mouse chromosome substitution strains

The genetic contribution of additive versus non-additive (epistatic) effects in the regulation of complex traits is unclear. While genome-wide association studies typically ignore gene-gene interactions, in part because of the lack of statistical power for detecting them, mouse chromosome substitution strains (CSSs) represent an alternate and powerful model for detecting epistasis given their limited allelic variation. Therefore, we utilized CSSs to identify and map both additive and epistatic loci that regulate a range of hematologic- and metabolism-related traits, as well as hepatic gene expression. Quantitative trait loci (QTLs) were identified using a CSS-based backcross strategy involving the segregation of variants on the A/J-derived substituted chromosomes 4 and 6 on an otherwise C57BL/6J genetic background. In the liver transcriptomes of offspring from this cross, we identified and mapped additive QTLs regulating the hepatic expression of 768 genes, and epistatic QTL pairs for 519 genes. Similarly, we identified additive QTLs for fat pad weight, platelets, and the percentage of granulocytes in blood, as well as epistatic QTL pairs controlling the percentage of lymphocytes in blood and red cell distribution width. The variance attributed to the epistatic QTL pairs was approximately equal to that of the additive QTLs; however, the SNPs in the epistatic QTL pairs that accounted for the largest variances were undetected in our single locus association analyses. These findings highlight the need to account for epistasis in association studies, and more broadly demonstrate the importance of identifying genetic interactions to understand the complete genetic architecture of complex traits.

genetics↗

bioRxiv2020

What is the storage effect, why should it occur in cancers, and how can it inform cancer therapy?

Intratumor heterogeneity is a feature of cancer that is associated with progression, treatment resistance, and recurrence. However, the mechanisms that allow diverse cancer cell lineages to coexist remain poorly understood. The storage effect is a coexistence mechanism that has been proposed to explain the diversity of a variety of ecological communities, including coral reef fish, plankton and desert annual plants. Three ingredients are required for there to be a storage effect: 1) temporal variability in the environment, 2) buffered population growth, and 3) species-specific environmental responses. Here, we argue that these conditions are observed in cancers and that it is likely that the storage effect contributes to intratumor diversity. Data that show the temporal variation within the tumor microenvironment is needed to quantify how cancer cells respond to fluctuations in the tumor microenvironment and what impact this has on interactions among cancer cell types. The presence of a storage effect within a patients tumors could have substantial impact on how we understand and treat cancer.

cancer biology↗

bioRxiv2020

Physiological properties and tailored feeds to support aquaculture of marbled crayfish in closed systems

The marbled crayfish (Procambarus virginalis) is a recently discovered freshwater crayfish species, which reproduces by apomictic parthenogenesis, resulting in a monoclonal, all-female population. The animals have become a popular source for nutritional protein in Madagascar and are increasingly being considered for commercial aquaculture. However, their potential has remained unclear and there are also significant ecological concerns about their anthropogenic distribution. We show here that the size and weight of marbled crayfish is comparable to commonly farmed freshwater crayfish. Furthermore, chemical analysis revealed a high chitin content in the marbled crayfish exoskeleton, which is a valuable source for the synthesis of chitosan and bioplastics. To allow the further evaluation of the animals in closed aquaculture systems, we developed tailored feeds that revealed an important role of methionine supplementation for animal growth. Additional analysis revealed a feed conversion rate of 1.4, which compares favorably to leading livestock for sustainable food production. Finally, we provide a concept for ecologically safe marbled crayfish aquaculture, based on key physiological characteristics that mitigate the invasive potential of the animals.

physiology↗