bioRxiv Science⌕ Search

Biology subjects

Müller, C.

Publications and source records attributed to Müller, C..

At least 19 recordsLinked to original sources
bioRxiv2026

Effects of Drought, Followed by Waterlogging, on Biomass, Leaf Physiology and Chemistry of Wheat Partly Depend on Fertilisation

Drought and waterlogging are prominent climate change challenges that, alone or in sequence, pronouncedly constrain agricultural crop production. A better understanding of relationships between water availability and nutrition regarding plant functioning is needed to optimise fertilisation under these challenges. We investigated impacts of drought, waterlogging and drought followed by waterlogging under two fertilisation regimes (low, normal) on various traits of wheat (Triticum aestivum). Next to biomass and photosynthesis measurements, cross-platform metabolomics was applied for in-depth metabolic analyses of flag leaves. We found detrimental effects of drought and drought-waterlogging on shoot and root biomass, especially at normal fertilisation, while photosynthetic traits were not or only slightly affected. Foliar nitrogen contents were higher in plants exposed to drought or to drought-waterlogging. Numerous primary and specialised metabolites were modulated by fertilisation and/ or watering. In particular, amino acids, benzoxazinoids and flavonoids were affected by fertilisation. Due to watering especially several amino acids changed in concentrations, with the induction pattern partly depending on fertilisation. Our study deepens the understanding of the interplay between water and nutrient availabilities as well as nutritional demands, growth and metabolism of wheat. This is highly relevant to balance sustainable agricultural nutrient management under the challenges of ongoing climate change.

ecology↗
bioRxiv2026

Molecular sources of monoterpenoid chemodiversity in the Asteraceae Tanacetum vulgare suggest a new model for the evolution of specialized metabolism

Highly diversified specialized metabolism enables plant communication with pollinators, herbivores, and protectors1-4. Its chemodiversity, under which evenness, richness and variation is summarized5-7, includes many compounds without known function1-4 and presents an evolutionary conundrum about how and what is selected for8,9. Due to its complexity, it is frequently unknown how it is encoded in genomes. To produce population level chemodiversity, the traits need to allow for highly chemodiverse and highly specific individuals in the same population. Here we use metabolomics, transcriptomics, and genomics combined with field analyses and functional assays of monoterpene synthases in the Asteraceae Tanacetum vulgare (tansy) and identify forces which produce high population level chemodiversity: selection for product specificity in enzymes, loss-of-expression alleles, absence variation, and specialized metabolism islands drive individuals towards low chemodiversity while unlinked enzyme loci, expression variation alleles, presence variation, and de novo enzyme evolution enable high individual chemodiversity. Since the molecular data suggests selection for mechanisms that increase chemodiversity itself at the population level, the screening hypothesis which posited plants produce a reservoir of diverse chemicals prior to selection8 should be replaced by a chemodiversity selection hypothesis. The results demonstrate that, in addition to plant protection via individual chemicals with known targeting mechanisms for predators, being different from your neighbors even if you are closely related is likely an important element in plant protection.

plant biology↗
bioRxiv2026

Antizyme regulates polyamine uptake via ATP13A3

Intracellular polyamine levels are tightly regulated and frequently elevated in cancer. While the regulation of polyamine synthesis is well characterized, the regulation of polyamine uptake is poorly understood. Here we identify ATP13A3 as a plasma membrane polyamine transporter. An increase in intracellular polyamine levels, due to polyamine supplementation or induction of polyamine synthesis, causes rapid internalization of the transporter and inhibition of polyamine uptake. Mechanistically, increased polyamine concentrations lead to expression of antizyme (AZ) which binds ATP13A3 and triggers its internalization. Mutations in the AZ binding site of ATP13A3 prevent AZ binding and lead to polyamine toxicity through uncontrolled polyamine influx. These findings establish ATP13A3 as a key polyamine transporter and provide a framework for targeting polyamine metabolism in cancer.

cell biology↗
bioRxiv2026

Aphids capture plant inter- and intraspecific chemodiversity

The role of chemodiversity in plant-insect interactions is widely recognised. However, our understanding of the extent to which chemodiversity connects both partners remains limited. Here, we investigated how aphid chemistry is linked to their plant diet and whether aphids capture plant inter- and intraspecific chemodiversity. Up to 93% of aphid chemical features were detected in plants. Untargeted metabolomics of aphids feeding on diets composed of distinct species or chemotypes within species unveiled the aphid capacity to capture inter- and intraspecific chemodiversity. Multiple chemodiversity indices and metabolic features significantly tracked diet variation and plant chemotypes were reflected in aphid metabolites. These features included phenolics and amino acids, likely ingested with the phloem sap, and fatty acids and terpenoids, potentially captured from the leaf surface. Overall, these findings expand our knowledge of the aphid plant-derived chemical repertoire and highlight that plant chemodiversity can be transmitted, supporting the need for chemodiversity preservation programs.

ecology↗
bioRxiv2026

Impacts of different types of florivores on flower metabolomes in the field

O_LIHerbivory is a major biotic stress for plants, triggering the induction and modulation of diverse specialized metabolites. Such induction responses are well studied for leaves and have been shown to depend on the herbivore feeding mode. Little is known about changes in flower metabolites and chemodiversity due to florivory type. Moreover, we lack an understanding of the intraspecific variation in such responses and whether these are spatially structured. C_LIO_LIThe aromatic plant Tanacetum vulgare, which shows high intraspecific chemodiversity in terpene profiles, was used to examine chemotype-specific metabolic responses of flower heads to infestation by the inflorescence-infesting aphid Macrosiphoniella tanacetaria or the flower-feeding beetle Olibrus spp. under field conditions. At peak flowering, each plant received both florivory treatments on separate stems, leaving one stem herbivore-free as a control. After four days, flower heads were harvested to analyze terpenes (GC-MS) and metabolic fingerprints (LC-MS). C_LIO_LIWe found stem-specific floral metabolic responses, with florivory altering specific chemical families and their chemodiversity. Levels of a few terpenes decreased following infestation, while none increased. Untargeted analyses revealed that aphid infestation had a lower effect on flower chemistry than beetle infestation, with aphid infestation mainly causing decreases and beetle infestation predominantly leading to increases in some metabolite intensities, but little overlap across treatments and chemotypes. C_LIO_LIOur results demonstrate that floral metabolic responses to florivory are spatially structured, florivore type-specific and shaped by plant chemotype. These findings highlight that the interplay between vascular organization, insect feeding mode, and intraspecific chemodiversity governs how flowers adjust their chemical defenses. C_LI One-sentence summaryTanacetum vulgare showed chemotype-specific responses to florivory by aphids (Macrosiphoniella tanacetaria) and beetles (Olibrus spp.), with aphids causing decreased and beetles increased levels of metabolic features within the same plant individuals, with little overlap in significant features across chemotypes.

plant biology↗
bioRxiv2026

Paleometabolomics reveals impacts of abiotic factors on rodent midden metabolism over the last 50,000 years.

Metabolomics and paleoecology combined can reveal how past ecosystems worked, helping us predict future changes more accurately. Pioneering studies are needed to shed light on the potential of the so-called paleometabolomics and to standardise its application. Here, we deployed an untargeted metabolomic workflow on a timeline (200 to 49,600 cal yr BP) of rodent middens that efficiently and reproducibly captured rodent midden metabolic diversity, recovering 79% of the richness detected in 15 contemporary plant species. We found that midden chemical diversity and metabolites were influenced by the midden composition, age, and environment. Variation at the metabolite level in middens could fit age, past temperature and precipitation levels with an R{superscript 2} > 88% and their plant composition. Compounds and families responding to climate variation included lipids (e.g. glycerophospholipids) and other metabolites linked to redox status such as phenolics (e.g. flavonoids, lignans). The responses of significant midden chemical indices and compounds to abiotic pressures were supported by their response in plants collected near the midden sites to temperature and soil water content across an elevation gradient. Overall, our results not only showcase paleometabolomics as a powerful tool to reconstruct past ecosystem dynamics and metabolic evolutionary trajectories, but also to uncover relevant chemical families that could serve as trackers of past -and potentially future- climate fluctuations.

ecology↗
bioRxiv2026

Metabolism and chemical diversity evolve in response to pollinator availability

Phytochemistry is a core player in shaping plant-pollinator networks and pollination services. Yet, little is known about the dynamic evolution of phytochemical traits in response to limited pollinator access, especially concerning chemical diversity. We combined an evolutionary experiment manipulating pollinator access with predictive metabolomics to uncover evolutionary changes in phytochemical traits of Brassica rapa. Our results unveiled chemical changes in both leaf and flower chemistry. Moreover, plants under selection by limited pollinator access showed a decreased chemical richness and diversity and a modulated primary and specialised metabolism, which could be used to predict pollinator access with 88% accuracy. Chemical indices and metabolites responding to pollinator access were associated with variation in flowering time and performance of outcrossing flowers. Our findings provide key insights into the influence of pollinator access on plant chemistry and indicate a risk of pollinator decline and losses of chemical diversity for plant-pollinator network structure and ecosystem dynamics.

ecology↗
bioRxiv2025

Development and structure-guided characterization of a novel ACE2-binding macrocyclic peptide

Angiotensin-converting enzyme 2 (ACE2) is a key node in the protective axis of the renin-angiotensin-aldosterone system (RAAS) for blood pressure and hydroelectrolyte regulation, and the main protein receptor recognized by the spike glycoproteins of the severe acute respiratory syndrome (SARS) coronaviruses (CoV) SARS-CoV and SARS-CoV-2. We identified the macrocyclic peptide WJL-63, developed using mRNA display, with high ACE2-binding affinity. The peptide was characterized in vitro in terms of purity, stability, hydrophilicity and ACE2 binding. The crystal structure of the extracellular region of ACE2 in complex with the peptide at 2.2 [A] resolution was elucidated. The structure revealed a binding mode in which WJL-63 is accommodated towards one side of the wide catalytic cleft of the ACE2 peptidase domain, with no direct contact to the conserved zinc ion site. WJL-63 residues Q4, R7, R11 and R14 anchor the peptide deep inside the binding pocket. The opposite edges of the peptide were found to be in contact with subdomain 1 and subdomain 2 of the peptidase domain. This upright binding mode requires an open ACE2 conformation, in contrast to small molecule carboxypeptidase inhibitors, which typically bind to the closed conformation of the enzyme. As a consequence of the open conformation binding mode, the front edge of WJL-63 is accessible for modification such as the herein reported conjugation of a chelator for radiometal labeling. The radiolabeled DOTA-WJL-63 was evaluated on ACE2-transfected HEK cells on which it revealed relatively strong binding with a KD value of 90 {+/-} 28 nM. WJL-63 provides a strong basis for the development of new classes of compounds for the modulation of ACE2 conformation, and for the development of imaging agents for the visualization of ACE2, for example in fluorescence or electron microscopy, or positron emission tomography (PET) imaging.

molecular biology↗
bioRxiv2025

Can Pupillometry Reveal Perturbation Detection in Sensorimotor Adaptation during Grasping?

Humans adjust their motor actions to correct for errors both with and without being aware of doing so. Little is known, however, about what makes errors detectable for the actor. Here, we replicate and extend prior work showing that motor adjustments may mask the very errors they correct for. We also investigated pupillometry as an unobtrusive no-report marker of perturbation detection. N=48 participants grasped objects while a visuo-haptic size mismatch was applied either sinusoidally or abruptly. When mismatches started abruptly and thereafter stayed the same, participants adapted well but also showed decreasing discrimination performance and decreasing confidence in their responses. This was not the case for sinusoidally introduced perturbations. We also show that parameters that characterize phasic and tonic pupil responses were predicted by stimulus parameters and differed depending on participants grasping and behavioral responses. However, predicting response characteristics from pupil-dilation features using support-vector machine classifiers was not successful. This shows that while pupillometry may yet prove to be a useful no-report marker of perturbation and error detection, there are some challenges for trial-by-trial prediction. New and NoteworthyAn actor detecting the need to adjust a motor action can make these adjustments more efficient. We show that error signals play a central role in both humans detection of and meta-cognition about motor perturbations. Pupil dilation during perturbed actions reflected perturbation properties and participants responses, but trial-wise prediction of responses using pupil-dilation parameters was close to chance. This is a step towards determining whether pupillometry can serve as a no-report marker of perturbation detection.

neuroscience↗
bioRxiv2025

BTRR complex deficiency is a driver for genomic instability in Bloom syndrome

Biallelic loss-of-function (LoF) variants in the BTRR complex members BLM, TOP3A, RMI1, and RMI2 cause Bloom syndrome (BSyn). The BTRR complex mainly acts on DNA replication and DNA repair processes, and dysfunction of this complex underlies the increased genomic instability and cancer predisposition associated with the BSyn phenotype. Here, we report CRISPR/Cas9-based genome-edited isogenic induced pluripotent stem cell (iPSC) models with compound heterozygous LoF variants in BLM, TOP3A, and RMI1. The cellular phenotype of all three BTRR-deficient iPSC lines included chromosome segregation defects, increased sister chromatid exchange rates, and impaired DNA single-strand template repair. Using single-cell whole genome sequencing, we showed that BTRR complex deficiency causes increased genome copy number alterations (CNAs) and, therefore, is a driver for genomic instability. CNA load was further induced by applying replication stress, and we observed that BTRRKO iPSCs acquired fewer de novo CNA events compared to wild-type cells, suggesting a possible selection loss against cells with high levels of DNA damage. Importantly, stress-induced and non-stress-induced CNAs in single-cell genomes were not stochastically distributed throughout the genome, but instead enriched at fragile sites. This finding might offer an opportunity for the development of novel NGS-based approaches to measure rates of genomic instability in disease conditions.

genetics↗
bioRxiv2024

Production of biologically active human basic Fibroblast Growth Factor (hFGFb) using Nicotiana tabacum transplastomic plants

The use of plants as biofactories presents as an attractive technology with the potential to efficiently produce high-value human recombinant proteins in a cost-effective manner. Plastid genome transformation stands out for its possibility to accumulate recombinant proteins at elevated levels. Of particular interest are recombinant growth factors, given their applications in animal cell culture and regenerative medicine. In this study we produced recombinant human Fibroblast Growth Factor (rhFGFb), a crucial protein required for animal cell culture, in tobacco chloroplasts. We successfully generated two independent transplastomic lines that are homoplasmic and accumulate rhFGFb in their leaves. Furthermore, the produced rhFGFb demonstrated its biological activity by inducing proliferation in HEK293T cell lines. These results collectively underscore plastid genome transformation as a promising plant-based bioreactor for rhFGFb production. Main conclusionWe generated transplastomic tobacco lines that stably express a human Basic Fibroblast Growth Factor (hFGFb) in their chloroplasts stroma and purified a biologically active recombinant hFGFb.

bioengineering↗
bioRxiv2024

Unraveling the genetic legacy of commercial whaling in bowhead whales and narwhals

Commercial whaling decimated many whale populations over several centuries. Bowhead whales (Balaena mysticetus) and narwhal (Monodon monoceros) have similar habitat requirements and are often seen together in the Canadian Arctic. Although their ranges overlap extensively, bowhead whales experienced significantly greater whaling pressure than narwhals. The different harvest histories but similar habitat requirements of these two species provide an opportunity to examine the demographic and genetic consequences of commercial whaling. We whole-genome resequenced Canadian Arctic bowhead whales and narwhals to delineate population structure and reconstruct demographic history. Bowhead whale effective population size sharply declined contemporaneously with the intense commercial whaling period. Narwhals instead exhibited recent growth in effective population size, reflecting limited opportunistic commercial harvest. Although the genetic diversity of bowhead whales and narwhals was similar, bowhead whales had more genetic diversity prior to commercial whaling and will likely continue to experience significant genetic drift in the future. In contrast, narwhals appear to have had long-term low genetic diversity and may not be at imminent risk of the consequences of the erosion of genetic diversity. This work highlights the importance of considering population trajectories in addition to genetic diversity when assessing the genetics of populations for conservation and management purposes.

genomics↗
bioRxiv2023

Plant metabolites modulate animal social networks and lifespan

Social interactions influence disease spread, information flow, and resource allocation across species, yet heterogeneity in social interaction frequency and its fitness consequences remain poorly understood. Additionally, animals can utilize plant metabolites for purposes beyond nutrition, but whether that shapes social networks is unclear. Here, we investigated how non-nutritive plant metabolites impact social interactions and the lifespan of the turnip sawfly, Athalia rosae. Adult sawflies acquire neo-clerodane diterpenoids (clerodanoids) from non-food plants, showing intraspecific variation in natural populations and laboratory-reared individuals. Clerodanoids can also be transferred between conspecifics, leading to increased agonistic social interactions. Network analysis indicated increased social interactions in sawfly groups where some or all individuals had prior access to clerodanoids. Social interaction frequency varied with clerodanoid status, with fitness costs including reduced lifespan resulting from increased interactions. Our findings highlight the role of intraspecific variation in the acquisition of non-nutritional plant metabolites in shaping social networks, with fitness implications on individual social niches.

animal behavior and cognition↗
bioRxiv2023

Maternal sterol 27-hydroxylase is crucial for securing fetal development

The maternal body helps in providing nutrients and degrading toxic metabolites instead of the fetal body; disruptions in these mechanisms affect normal fetal development. Sterol 27-hydroxylase (Cyp27a1) is involved in the alternative pathway of bile acid synthesis, which is enhanced during pregnancy. However, its role in fetal development remains unclear. Here, we demonstrate that maternal Cyp27a1 activity is essential for progression of normal pregnancy and fetal organ formation. Depletion of maternal Cyp27a1 reduced the pregnancy rate and litter size. Newborn mice died of respiratory distress syndrome resulting from the absence of mature alveolar epithelial cells. These phenotypes were caused by 7-hydroxycholesterol (7-HC) accumulating in Cyp27a1-deficient mice. Mechanistically, 7-HC destabilized the Fau protein, mediating ribosome assembly, the downregulation of which caused poor polysome formation, lower protein synthesis, and impaired lung maturation. Overall, this study revealed an essential mechanism of securing fetal development by degrading a toxic metabolite in the maternal body.

developmental biology↗
bioRxiv2023

Discarded sequencing reads uncover natural variation in pest resistance in Thlaspi arvense

Understanding the genomic basis of natural variation in plant pest resistance is an important goal in plant science, but it usually requires large and labour-intensive phenotyping experiments. Here, we explored the possibility that non-target reads from plant DNA sequencing can serve as phenotyping proxies for addressing such questions. We used data from a whole-genome and -epigenome sequencing study of 207 natural lines of field pennycress (Thlaspi arvense) that were grown in a common environment and spontaneously colonized by aphids, mildew and other microbes. We found that the numbers of non-target reads assigned to the pest species differed between populations, had significant SNP-based heritability, and were associated with climate of origin and baseline glucosinolates content. Specifically, pennycress lines from cold and thermally fluctuating habitats, presumably less favorable to aphids, showed higher aphid DNA load, i.e. decreased aphid resistance. Genome-wide association analyses identified genetic variants at known defense genes but also novel genomic regions associated with variation in aphid and mildew DNA load. Moreover, we found several differentially methylated regions associated with pathogen loads, in particular differential methylation at transposons and hypomethylation in the promoter of a gene involved in stomatal closure, likely induced by pathogens. Our study provides first insights into the defense mechanisms of Thlaspi arvense, a rising crop and model species, and demonstrates that non-target whole genome sequencing reads, usually discarded, can be leveraged to estimate intensities of plant biotic interactions. With rapidly increasing numbers of large sequencing datasets worldwide, this approach should have broad application in fundamental and applied research.

evolutionary biology↗
bioRxiv2023

Convergent and divergent responses of the rhizosphere chemistry and bacterial communities to a stress gradient in the Atacama Desert.

Plants can modulate their rhizosphere chemistry, thereby influencing microbe communities. Although our understanding of rhizosphere chemistry is growing, knowledge of its responses to abiotic constraints is limited, especially in realistic ecological contexts. Here, we combined predictive metabolomics with bacterial sequencing data to investigate whether rhizosphere chemistry responded to environmental constraints and shaped bacterial communities across an elevation gradient in the Atacama Desert. We found that metabolic adjustments of rhizosphere chemistry predicted the environment of four plant species independently of year, identifying important rhizosphere metabolic biomarkers. Inter-species predictions unveiled significant biochemical convergences. Subsequently, we linked metabolic predictors to variation in the abundance of operational taxonomic units (OTUs). Chemical response influenced distinct and common bacterial families between species and vegetation belts. The annotation of chemical markers and correlated bacterial families highlighted critical biological processes such as nitrogen starvation, metal pollution and plant development and defence. Overall, this study demonstrates a unique metabolic set likely involved in improving plant resilience to harsh edaphic conditions. Besides, the results emphasise the need to integrate ecology with plant metabolome and microbiome approaches to explore plant-soil interactions and better predict their responses to climate change and consequences for ecosystem dynamics.

ecology↗
bioRxiv2023

Oncogenic functions of the m6A demethylase FTO in breast cancer cells involving translational upregulation of C/EBPβ-LIP

N6-methyladenosine (m6A) is a prevalent posttranscriptional mRNA modification involved in the regulation of transcript turnover, translation, and other aspects of RNA fate. The modification is mediated by multicomponent methyltransferase complexes (so-called writers) and is reversed through the action of the m6A-demethylases fat mass and obesity-associated (FTO) and alkB homolog 5 (ALKBH5) (so-called erasers). FTO promotes cell proliferation, colony formation and metastasis in models of triple-negative breast cancer (TNBC). However, little is known about genome-wide or specific downstream regulation by FTO. Here, we examined changes in the genome-wide transcriptome and translatome following FTO-knockdown in TNBC cells. Unexpectedly, FTO knockdown had a limited effect on the translatome, while transcriptome analysis revealed that genes related to extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) are being regulated through yet unidentified mechanisms. Differential translation of the CEBPB mRNA into the C/EBP{beta} transcription factor isoform C/EBP{beta}-LIP is known to act pro-oncogenic in TNBC cells through regulation of EMT genes. Here we show that FTO is required for efficient C/EBP{beta}-LIP expression, suggesting that FTO has oncogenic functions through regulation of C/EBP{beta}-LIP.

cancer biology↗
bioRxiv2023

Understanding the phytochemical diversity of plants: Quantification, variation and ecological function

Plants produce a great number of phytochemical compounds mediating a variety of different functions. Recently, phytochemical diversity (chemodiversity), a way which to quantify the complex phenotype formed by sets of phytochemicals, has been suggested to be important for function. However, no study has systematically examined the potential (in)direct functional importance of chemodiversity on a general level, partly due to a lack of an agreement on how to quantify this aspect of the plant phenotype. This paper has four aims: 1) We discuss how chemodiversity (deconstructed into components of richness, evenness and disparity) may quantify different aspects of the phenotype that are ecologically relevant. 2) We systematically review the literature on chemodiversity to examine methodological practices, explore ecological patterns of variability in diversity across different levels of biological organization, and investigate the functional role of this diversity in interactions between plants and other organisms. 3) We provide a framework facilitating decisions on which measure of chemodiversity is best used in different contexts. 4) We outline open questions and avenues for future research in this area. A more thorough understanding of phytochemical diversity will increase our knowledge on the functional role phytochemical compounds, and how they shape ecological interactions between plants and their environment.

ecology↗