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Research is the vital expression of humankind’s most important qualities: curiosity and imagination.

Explorers, inventors, pioneers—dedicated researchers on the frontiers of science and the humanities.

Insight, when it comes, changes everything.

Publications

The NOMIS community of researchers and partners is instrumental in driving interdisciplinary collaboration, generating insights and ultimately advancing our understanding of the world. A key component of these efforts is knowledge sharing. Comprising a unique offering of engaging scientific lectures, insightful films about our awardees’ research, and a comprehensive publication database, NOMIS Insights are designed to facilitate the sharing of knowledge. They showcase the groundbreaking findings and innovative perspectives born from NOMIS-supported research endeavors, embodying our dedication to enabling scientific progress.

Our NOMIS Insight database provides a comprehensive source of all publications resulting from NOMIS-supported research projects.

Single-cell RNA-sequencing reveals early mitochondrial dysfunction unique to motor neurons shared across FUS- and TARDBP-ALS

NOMIS Researcher(s)

Published in

May 19, 2025

Mutations in FUS and TARDBP cause amyotrophic lateral sclerosis (ALS), but the precise mechanisms of selective motor neuron degeneration remain unresolved. To address if pathomechanisms are shared across mutations and related to either gain- or loss-of-function, we performed single-cell RNA sequencing across isogenic induced pluripotent stem cell-derived neuron types, harbouring FUS P525L, FUS R495X, TARDBP M337V mutations or FUS knockout. Transcriptional changes were far more pronounced in motor neurons than interneurons. About 20% of uniquely dysregulated motor neuron transcripts were shared across FUS mutations, half from gain-of-function. Most indicated mitochondrial impairments, with attenuated pathways shared with mutant TARDBP M337V as well as C9orf72-ALS patient motor neurons. Mitochondrial motility was impaired in ALS motor axons, even with nuclear localized FUS mutants, demonstrating shared toxic gain-of-function mechanisms across FUS- and TARDBP-ALS, uncoupled from protein mislocalization. These early mitochondrial dysfunctions unique to motor neurons may affect survival and represent therapeutic targets in ALS.

Research field(s)
Molecular Biology, Neuroscience, Biochemistry & Molecular Biology

DOI
10.1038/s41467-025-59679-1

Small-molecule dissolution of stress granules by redox modulation benefits ALS models

NOMIS Researcher(s)

Published in

May 14, 2025

Neurodegenerative diseases, such as amyotrophic lateral sclerosis, are often associated with mutations in stress granule proteins. Aberrant stress granule condensate formation is associated with disease, making it a potential target for pharmacological intervention. Here, we identified lipoamide, a small molecule that specifically prevents cytoplasmic condensation of stress granule proteins. Thermal proteome profiling showed that lipoamide stabilizes intrinsically disordered domain-containing proteins, including SRSF1 and SFPQ, which are stress granule proteins necessary for lipoamide activity. SFPQ has redox-state-specific condensate dissolving behavior, which is modulated by the redox-active lipoamide dithiolane ring. In animals, lipoamide ameliorates aging-associated aggregation of a stress granule reporter protein, improves neuronal morphology and recovers motor defects caused by amyotrophic lateral sclerosis-associated FUS and TDP-43 mutants. Thus, lipoamide is a well-tolerated small-molecule modulator of stress granule condensation, and dissection of its molecular mechanism identified a cellular pathway for redox regulation of stress granule formation.

Research field(s)
Neuroscience, Biochemistry & Molecular Biology

DOI
10.1038/s41589-025-01893-5

Binary climate data visuals amplify perceived impact of climate change

NOMIS Researcher(s)

Published in

April 17, 2025

For much of the global population, climate change appears as a slow, gradual shift in daily weather. This leads many to perceive its impacts as minor and results in apathy (the ‘boiling frog’ effect). How can we convey the urgency of the crisis when its impacts appear so subtle? Here, through a series of large-scale cognitive experiments (N = 799), we find that presenting people with binary climate data (for example, lake freeze history) significantly increases the perceived impact of climate change (Cohen’s d = 0.40, 95% confidence interval 0.26–0.54) compared with continuous data (for example, mean temperature). Computational modelling and follow-up experiments (N = 398) suggest that binary data enhance perceived impact by creating an ‘illusion’ of sudden shifts. Crucially, our approach does not involve selective data presentation but rather compares different datasets that reflect equivalent trends in climate change over time. These findings, robustly replicated across multiple experiments, provide a cognitive basis for the ‘boiling frog’ effect and offer a psychologically grounded approach for policymakers and educators to improve climate change communication while maintaining scientific accuracy.

Research field(s)
Information & Communication Technologies, Psychology & Cognitive Sciences, Behavioral Science & Comparative Psychology

DOI
10.1038/s41562-025-02183-9

DNA binding and mitotic phosphorylation protect polyglutamine proteins from assembly formation

NOMIS Researcher(s)

Published in

April 15, 2025
Polyglutamine (polyQ) expansion is associated with pathogenic protein aggregation in neurodegenerative disorders. However, long polyQ tracts are also found in many transcription factors (TFs), such as FOXP2, a TF implicated in human speech. Here, we explore how FOXP2 and other glutamine-rich TFs avoid unscheduled assembly. Throughout interphase, DNA binding, irrespective of sequence specificity, has a solubilizing effect. During mitosis, multiple phosphorylation events promote FOXP2’s eviction from chromatin and supplant the solubilizing function of DNA. Further, human-specific amino acid substitutions linked to the evolution of speech map to a mitotic phospho-patch, the “EVO patch,” and reduce the propensity of the human FOXP2 to assemble. Fusing the pathogenic form of Huntingtin to either a DNA-binding domain, a phosphomimetic variant of this EVO patch, or a negatively charged peptide is sufficient to diminish assembly formation, suggesting that hijacking mechanisms governing solubility of glutamine-rich TFs may offer new strategies for treatment of polyQ expansion diseases.

Research field(s)
Neuroscience, Biochemistry & Molecular Biology, Genetics & Heredity, Evolutionary Biology

DOI
10.1016/j.cell.2025.03.031

Comprehensive interrogation of synthetic lethality in the DNA damage response

NOMIS Researcher(s)

Published in

April 9, 2025

The DNA damage response (DDR) is a multifaceted network of pathways that preserves genome stability1,2. Unravelling the complementary interplay between these pathways remains a challenge3,4. Here we used CRISPR interference (CRISPRi) screening to comprehensively map the genetic interactions required for survival during normal human cell homeostasis across all core DDR genes. We captured known interactions and discovered myriad new connections that are available online. We defined the molecular mechanism of two of the strongest interactions. First, we found that WDR48 works with USP1 to restrain PCNA degradation in FEN1/LIG1-deficient cells. Second, we found that SMARCAL1 and FANCM directly unwind TA-rich DNA cruciforms, preventing catastrophic chromosome breakage by the ERCC1–ERCC4 complex. Our data yield fundamental insights into genome maintenance, provide a springboard for mechanistic investigations into new connections between DDR factors and pinpoint synthetic vulnerabilities that could be exploited in cancer therapy.

Partnership(s)
,

Research field(s)
Bioinformatics, Biochemistry & Molecular Biology, Genetics & Heredity, Oncology & Carcinogenesis

DOI
10.1038/s41586-025-08815-4

Glacier-fed stream diatoms (Bacillariophyta) from the Rwenzori Mountains, Uganda, with the description of one new species from the genus Neidium

NOMIS Researcher(s)

Published in

April 8, 2025

Glacier-fed streams (GFSs) are harsh environments hosting unique, highly specialized communities. Interestingly, glaciers and their GFSs are also present in Earth’s tropical regions, where environmental characteristics contrast with GFS conditions elsewhere. Yet, despite the unique and isolated nature of tropical GFSs, little is known about their inhabitants, even though they may disappear later this century with ongoing climate change. Here, we examined diatom communities from one of the last tropical African GFSs in the Rwenzori Mountains, Uganda, to characterize the composition and diversity of this unique system. Six sediment-associated biofilm samples were collected from two reaches of a stream draining the Mt. Stanley Glacier, and the resident diatom communities were studied morphologically using light and scanning electron microscopy, as well as through the sequencing of amplicons from extracted DNA (18S and rbcL). In general, morphological results agree well with barcoding results, but each individually provides irreplaceable insights. In total, we identify 24 morphotypes utilizing light microscopy, 101 diatom Amplicon Sequence Variants (ASVs) using 18S sequences, and 65 ASVs with rbcL. Across approaches, common genera include Achnanthidium, Psammothidium, Neidium, Cymbopleura, Eunotia, and Pinnularia. However, only about half of the diversity could be assigned to the species level across methodologies, including several of the most common taxa, indicating a high level of uniqueness. Accordingly, one of the most common taxa encountered is described here as a new species, Neidium rwenzoriense sp. nov. Our results emphasize the Rwenzori Mountains as a global hotspot for endemism, and the novelty of disappearing tropical GFSs as diatom habitats.

Research field(s)
Conservation Biology, Ecology, Environmental Sciences

DOI
10.1080/0269249X.2025.2474765

Belief in belief: Even atheists in secular countries show intuitive preferences favoring religious belief

NOMIS Researcher(s)

Published in

March 27, 2025

We find evidence of belief in belief—intuitive preferences for religious belief over atheism, even among atheist participants—across eight comparatively secular countries. Religion is a cross-cultural human universal, yet explicit markers of religiosity have rapidly waned in large parts of the world in recent decades. We explored whether intuitive religious influence lingers, even among nonbelievers in largely secular societies. We adapted a classic experimental philosophy task to test for this intuitive belief in belief among people in eight comparatively nonreligious countries: Canada, China, Czechia, Japan, the Netherlands, Sweden, the United Kingdom, and Vietnam (total N = 3,804). Our analyses revealed strong evidence that 1) people intuitively favor religious belief over atheism and that 2) this pattern was not moderated by participants’ own self-reported atheism. Indeed, 3) even atheists in relatively secular societies intuitively prefer belief to atheism. These inferences were robust across different analytic strategies and across other measures of individual differences in religiosity and religious instruction. Although explicit religious belief has rapidly declined in these countries, it is possible that belief in belief may still persist. These results speak to the complex psychological and cultural dynamics of secularization.

Research field(s)
Philosophy & Theology, Psychology & Cognitive Sciences

DOI
10.1073/pnas.2404720122

Glaciers are not just blocks of ice — plans to save them mustn’t overlook their hidden life

NOMIS Researcher(s)

Published in

March 24, 2025

As glaciers begin to disappear, technological fixes to slow or halt ice melt are emerging. But regulations are urgently required before these fixes are used widely.

Research field(s)
Conservation Biology, Environmental Sciences

DOI
10.1038/d41586-025-00897-4

Microtubules in Asgard archaea

NOMIS Researcher(s)

Published in

March 21, 2025
Microtubules are a hallmark of eukaryotes. Archaeal and bacterial homologs of tubulins typically form homopolymers and non-tubular superstructures. The origin of heterodimeric tubulins assembling into microtubules remains unclear.
Here, we report the discovery of microtubule-forming tubulins in Asgard archaea, the closest known relatives of eukaryotes. These Asgard tubulins (AtubA/B) are closely related to eukaryotic α/β-tubulins and the enigmatic bacterial tubulins BtubA/B. Proteomics of Candidatus Lokiarchaeum ossiferum showed that AtubA/B were highly expressed. Cryoelectron microscopy structures demonstrate that AtubA/B form eukaryote-like heterodimers, which assembled into 5-protofilament bona fide microtubules in vitro. The additional paralog AtubB2 lacks a nucleotide-binding site and competitively displaced AtubB. These AtubA/B2 heterodimers polymerized into 7-protofilament non-canonical microtubules. In a sub-population of Ca. Lokiarchaeum ossiferum cells, cryo-tomography revealed tubular structures, while expansion microscopy identified AtubA/B cytoskeletal assemblies.
Our findings suggest a pre-eukaryotic origin of microtubules and provide a framework for understanding the fundamental principles of microtubule assembly.

Partnership(s)

Research field(s)
Molecular Biology, Evolutionary Biology, Microbiology

DOI
10.1016/j.cell.2025.02.027

Adrenaline for the early resuscitation of children with sepsis – a randomized controlled pilot study (ANDES CHILD): study protocol and analysis plan

NOMIS Researcher(s)

Published in

March 12, 2025

Purpose

Sepsis is a leading cause of pediatric morbidity and mortality worldwide. Current guidelines recommend fluid bolus administration of 40–60 mL/kg as part of initial resuscitation, despite limited evidence and concerns about potential harm from high fluid volumes. The ANDES-CHILD pilot study hypothesizes that early initiation of inotropes is feasible and reduces fluid use compared to standard resuscitation.

Methods

Multicenter open label randomized controlled pilot trial conducted in three Pediatric Emergency Departments in Latin America. Children aged 28 days to 18 years with presumed septic shock will be randomized in a 1:1 ratio to receive either early adrenaline infusion after 20 mL/kg fluid bolus versus standard resuscitation with 40–60 mL/kg fluid bolus prior to initiating inotropes. The primary outcome is feasibility, with survival free of organ support censored at 28 days as the exploratory primary clinical outcome. The study will enroll 40 patients, representing approximately 10% of a full trial, with follow-up at 28 days. Baseline characteristics, adverse events and protocol violations will be summarized descriptively. Outcomes will be analyzed using difference estimates with 95% confidence intervals. An intention-to-treat approach will be used for statistical analysis.

Discussion

This pragmatic pilot study will generate essential data to evaluate the feasibility and guide the design of a full trial aimed to assessing the benefits of early inotrope use in pediatric septic shock. The study was registered on ClinicalTrials.gov prior to the start of recruitment (NCT06478797). Recruitment started on July 18, 2024.

Research field(s)
Pediatrics

DOI
10.1007/s44253-025-00066-5

BMP-dependent patterning of ectoderm tissue material properties modulates lateral mesendoderm cell migration during early zebrafish gastrulation

NOMIS Researcher(s)

Published in

March 8, 2025

Cell migration is a fundamental process during embryonic development. Most studies in vivo have focused on the migration of cells using the extracellular matrix (ECM) as their substrate for migration. In contrast, much less is known about how cells migrate on other cells, as found in early embryos when the ECM has not yet formed. Here, we show that lateral mesendoderm (LME) cells in the early zebrafish gastrula use the ectoderm as their substrate for migration. We show that the lateral ectoderm is permissive for the animal-pole-directed migration of LME cells, while the ectoderm at the animal pole halts it. These differences in permissiveness depend on the lateral ectoderm being more cohesive than the animal ectoderm, a property controlled by bone morphogenetic protein (BMP) signaling within the ectoderm. Collectively, these findings identify ectoderm tissue cohesion as one critical factor in regulating LME migration during zebrafish gastrulation.

Partnership(s)
,

Research field(s)
Molecular Biology, Biophysics

DOI
10.1016/j.celrep.2025.115387

Strong charge-photon coupling in planar germanium enabled by granular aluminium superinductors

NOMIS Researcher(s)

Published in

March 1, 2025

High kinetic inductance superconductors are gaining increasing interest for the realisation of qubits, amplifiers and detectors. Moreover, thanks to their high impedance, quantum buses made of such materials enable large zero-point fluctuations of the voltage, boosting the coupling rates to spin and charge qubits. However, fully exploiting the potential of disordered or granular superconductors is challenging, as their inductance and, therefore, impedance at high values are difficult to control. Here, we report a reproducible fabrication of granular aluminium resonators by developing a wireless ohmmeter, which allows in situ measurements during film deposition and, therefore, control of the kinetic inductance of granular aluminium films. Reproducible fabrication of circuits with impedances (inductances) exceeding 13 kΩ (1 nH per square) is now possible. By integrating a 7.9 kΩ resonator with a germanium double quantum dot, we demonstrate strong charge-photon coupling with a rate of gc/2π = 566 ± 2 MHz. This broadly applicable method opens the path for novel qubits and high-fidelity, long-distance two-qubit gates.

Research field(s)
Nanoscience & Nanotechnology, Quantum

DOI
10.1038/s41467-025-57252-4

Large closed-basin lakes sustainably supplied phosphate during the origins of life

NOMIS Researcher(s)

Published in

February 19, 2025

The origin of life on Earth required a supply of phosphorus (P) for the synthesis of universal biomolecules. Closed lakes may have accumulated high P concentrations on early Earth. However, it is not clear whether prebiotic P uptake in such settings would then have been sustainable. We show that large closed-basin lakes can combine high P concentrations at steady state with extremely high rates of biological productivity. Our case study is Mono Lake in California, which has close to 1 millimolar dissolved P at steady state despite extremely high rates of biological productivity, in contrast to smaller closed basins where life is scarce. Hence, large closed-basin lakes offer an environment where high rates of prebiotic P productivity can plausibly coexist with high steady-state P concentrations. Such lakes should have readily formed on the heavily cratered and volcanically active surface of early Earth.

Partnership(s)
,

Research field(s)
Physics & Astronomy

DOI
10.1126/sciadv.adq0027

AI-based approach to dissect the variability of mouse stem cell-derived embryo models

NOMIS Researcher(s)

Published in

February 19, 2025

Recent advances in stem cell-derived embryo models have transformed developmental biology, offering insights into embryogenesis without the constraints of natural embryos. However, variability in their development challenges research standardization. To address this, we use deep learning to enhance the reproducibility of selecting stem cell-derived embryo models. Through live imaging and AI-based models, we classify 900 mouse post-implantation stem cell-derived embryo-like structures (ETiX-embryos) into normal and abnormal categories. Our best-performing model achieves 88% accuracy at 90 h post-cell seeding and 65% accuracy at the initial cell-seeding stage, forecasting developmental trajectories. Our analysis reveals that normally developed ETiX-embryos have higher cell counts and distinct morphological features such as larger size and more compact shape. Perturbation experiments increasing initial cell numbers further supported this finding by improving normal development outcomes. This study demonstrates deep learning’s utility in improving embryo model selection and reveals critical features of ETiX-embryo self-organization, advancing consistency in this evolving field.

Research field(s)
Bioinformatics, Artificial Intelligence & Image Processing, Biophysics, Developmental Biology

DOI
10.1038/s41467-025-56908-5

Fluoxetine promotes IL-10–dependent metabolic defenses to protect from sepsis-induced lethality

NOMIS Researcher(s)

Published in

February 14, 2025

Selective serotonin reuptake inhibitors (SSRIs) are some of the most prescribed drugs in the world. While they are used for their ability to increase serotonergic signaling in the brain, SSRIs are also known to have a broad range of effects beyond the brain, including immune and metabolic effects. Recent studies have demonstrated that SSRIs are protective in animal models and humans against several infections, including sepsis and COVID-19; however, the mechanisms underlying this protection are largely unknown. Here, we mechanistically link two previously described effects of the SSRI fluoxetine in mediating protection against sepsis. We show that fluoxetine-mediated protection is independent of peripheral serotonin and instead increases levels of circulating interleukin-10 (IL-10). IL-10 is necessary for protection from sepsis-induced hypertriglyceridemia, preventing cardiac effects including impairment of glucose oxidation, ectopic lipid accumulation, ventricular stretch and possibly cardiac failure. Our work reveals a beneficial “off-target” effect of fluoxetine, and reveals a protective immunometabolic defense mechanism with therapeutic potential.

Partnership(s)
,

Research field(s)
Biochemistry & Molecular Biology, Immunology, Pharmacology & Pharmacy, Microbiology

DOI
10.1126/sciadv.adu4034

Observation of Collapse and Revival in a Superconducting Atomic Frequency Comb

NOMIS Researcher(s)

Published in

February 11, 2025

Recent advancements in superconducting circuits have enabled the experimental study of collective behavior of precisely controlled intermediate-scale ensembles of qubits. In this work, we demonstrate an atomic frequency comb formed by individual artificial atoms strongly coupled to a single resonator mode. We observe periodic microwave pulses that originate from a single coherent excitation dynamically interacting with the multiqubit ensemble. We show that this revival dynamics emerges as a consequence of the constructive and periodic rephasing of the five superconducting qubits forming the vacuum Rabi split comb. In the future, similar devices could be used as a memory with in situ tunable storage time or as an on-chip periodic pulse generator with nonclassical photon statistics.

Research field(s)
Quantum

DOI
10.1103/PhysRevLett.134.063601

Visually guided in vivo single-cell electroporation for monitoring and manipulating mammalian hippocampal neurons

NOMIS Researcher(s)

Published in

February 10, 2025

Sparse, single-cell labeling approaches enable high-resolution, high signal-to-noise recordings from subcellular compartments and intracellular organelles and allow precise manipulations of individual cells and local circuits while minimizing complex changes associated with global network manipulations. However, thus far, only a limited number of approaches have been developed to label single cells with unique combinations of genetically encoded indicators, target deep cortical structures or sustainably use the same chronic preparation for weeks. Here we developed a method to deliver plasmids selectively to single pyramidal neurons in the mouse dorsal hippocampus using two-photon visually guided in vivo single-cell electroporation to address these limitations. This method allows long-term plasmid expression in a controlled number of individual pyramidal neurons, facilitating subcellular resolution imaging, intracellular organelle tracking, monosynaptic input mapping, plasticity induction and targeted whole-cell patch-clamp recordings.

Research field(s)
Neuroscience, Molecular Biology

DOI
10.1038/s41596-024-01099-4

Predicting climate-change impacts on the global glacier-fed stream microbiome

NOMIS Researcher(s)

Published in

February 1, 2025

The shrinkage of glaciers and the vanishing of glacier-fed streams (GFSs) are emblematic of climate change. However, forecasts of how GFS microbiome structure and function will change under projected climate change scenarios are lacking. Combining 2,333 prokaryotic metagenome-assembled genomes with climatic, glaciological, and environmental data collected by the Vanishing Glaciers project from 164 GFSs draining Earth’s major mountain ranges, we here predict the future of the GFS microbiome until the end of the century under various climate change scenarios. Our model framework is rooted in a space-for-time substitution design and leverages statistical learning approaches. We predict that declining environmental selection promotes primary production in GFSs, stimulating both bacterial biomass and biodiversity. Concomitantly, predictions suggest that the phylogenetic structure of the GFS microbiome will change and entire bacterial clades are at risk. Furthermore, genomic projections reveal that microbiome functions will shift, with intensified solar energy acquisition pathways, heterotrophy and algal-bacterial interactions. Altogether, we project a ‘greener’ future of the world’s GFSs accompanied by a loss of clades that have adapted to environmental harshness, with consequences for ecosystem functioning.

Research field(s)
Conservation Biology, Ecology, Environmental Sciences

DOI
10.1038/s41467-025-56426-4

Resolving the three-dimensional interactome of human accelerated regions during human and chimpanzee neurodevelopment

NOMIS Researcher(s)

Published in

January 30, 2025

Human accelerated regions (HARs) have been implicated in human brain evolution. However, insight into the genes and pathways they control is lacking, hindering the understanding of their function. Here, we identify 2,963 conserved gene targets for 1,590 HARs and their orthologs in human and chimpanzee neural stem cells (NSCs). Conserved gene targets are enriched for neurodevelopmental functions and are overrepresented among differentially expressed genes (DEGs) identified in human NSCs (hNSCs) and chimpanzee NSCs (cNSCs) as well as in human versus non-human primate brains. Species-specific gene targets do not converge on any function and are not enriched among DEGs. HAR targets also show cell-type-specific expression in the human fetal brain, including in outer radial glia, which are linked to cortical expansion. Our findings support that HARs influence brain evolution by altering the expression of ancestral gene targets shared between human and chimpanzee rather than by gaining new targets in human and facilitate hypothesis-directed studies of HAR biology.

Research field(s)
Bioinformatics, Developmental Biology, Evolutionary Biology

DOI
10.1016/j.cell.2025.01.007

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