Insight
is our reward

NOMIS Insights

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.

NOMIS Researcher(s)

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

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)
Molecular Biology, Neuroscience

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

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

NOMIS Researcher(s)

Published in

January 20, 2025

Science is crucial for evidence-based decision-making. Public trust in scientists can help decision makers act on the basis of the best available evidence, especially during crises. However, in recent years the epistemic authority of science has been challenged, causing concerns about low public trust in scientists. We interrogated these concerns with a preregistered 68-country survey of 71,922 respondents and found that in most countries, most people trust scientists and agree that scientists should engage more in society and policymaking. We found variations between and within countries, which we explain with individual- and country-level variables, including political orientation. While there is no widespread lack of trust in scientists, we cannot discount the concern that lack of trust in scientists by even a small minority may affect considerations of scientific evidence in policymaking. These findings have implications for scientists and policymakers seeking to maintain and increase trust in scientists.

Research field(s)
Sociology, Psychology & Cognitive Sciences, Social Psychology

NOMIS Researcher(s)

Published in

January 20, 2025

Science is integral to society because it can inform individual, government, corporate, and civil society decision-making on issues such as public health, new technologies or climate change. Yet, public distrust and populist sentiment challenge the relationship between science and society. To help researchers analyse the science-society nexus across different geographical and cultural contexts, we undertook a cross-sectional population survey resulting in a dataset of 71,922 participants in 68 countries. The data were collected between November 2022 and August 2023 as part of the global Many Labs study “Trust in Science and Science-Related Populism” (TISP). The questionnaire contained comprehensive measures for individuals’ trust in scientists, science-related populist attitudes, perceptions of the role of science in society, science media use and communication behaviour, attitudes to climate change and support for environmental policies, personality traits, political and religious views and demographic characteristics. Here, we describe the dataset, survey materials and psychometric properties of key variables. We encourage researchers to use this unique dataset for global comparative analyses on public perceptions of science and its role in society and policy-making.

Research field(s)
Social Sciences, Psychology & Cognitive Sciences, Social Psychology, Public Health

NOMIS Researcher(s)

Published in

January 14, 2025

Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.0005 mg kg−1—far below the detection limits of conventional whole body imaging techniques. We demonstrate that intramuscularly injected LNPs carrying SARS-CoV-2 spike mRNA reach heart tissue, leading to proteome changes, suggesting immune activation and blood vessel damage. SCP-Nano generalizes to various types of nanocarriers, including liposomes, polyplexes, DNA origami and adeno-associated viruses (AAVs), revealing that an AAV2 variant transduces adipocytes throughout the body. SCP-Nano enables comprehensive three-dimensional mapping of nanocarrier distribution throughout mouse bodies with high sensitivity and should accelerate the development of precise and safe nanocarrier-based therapeutics.

Research field(s)
Nanoscience & Nanotechnology, Biomedical Engineering

NOMIS Researcher(s)

Published in

January 9, 2025

The impacts of degradation and deforestation on tropical forests are poorly understood, particularly at landscape scales. We present an extensive ecosystem analysis of the impacts of logging and conversion of tropical forest to oil palm from a large-scale study in Borneo, synthesizing responses from 82 variables categorized into four ecological levels spanning a broad suite of ecosystem properties: (i) structure and environment, (ii) species traits, (iii) biodiversity, and (iv) ecosystem functions. Responses were highly heterogeneous and often complex and nonlinear. Variables that were directly impacted by the physical process of timber extraction, such as soil structure, were sensitive to even moderate amounts of logging, whereas measures of biodiversity and ecosystem functioning were generally resilient to logging but more affected by conversion to oil palm plantation.

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

Published in

January 9, 2025

The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid–CoA:amino acid N-acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti–programmed cell death protein 1 (anti–PD-1) immunotherapy. Furthermore, different BAs regulated CD8+ T cells differently; primary BAs induced oxidative stress, whereas the secondary BA lithocholic acid inhibited T cell function through endoplasmic reticulum stress, which was countered by ursodeoxycholic acid. We demonstrate that modifying BA synthesis or dietary intake of ursodeoxycholic acid could improve tumor immunotherapy in liver cancer model systems.

Research field(s)
Biomedical Research, Biochemistry & Molecular Biology, Microbiology, Immunology, Oncology & Carcinogenesis

NOMIS Researcher(s)

Adolescence is a developmental period of relative volatility, where the individual experiences significant changes to their physical and social environment. The ability to adapt to the volatility of one’s surroundings is an important cognitive ability, particularly while foraging, a near-ubiquitous behaviour across the animal kingdom. As adolescents experience more volatility in their surroundings, we predicted that this age group would be more adept than adults at using exploration to adjust to volatility. We employed a foraging task with a well-validated computational model to characterise the mechanisms of exploration in volatile environments, preregistering the hypothesis that adolescents (aged 16–17; N = 91) would exhibit more optimal adaptation of their learning rate to changes in environmental volatility compared with adults (aged 24+; N = 90). However, surprisingly, both adolescents and adults exhibited suboptimal adjustment of their learning rate to environmental volatility. In contrast to the learning rate, it was instead participants’ stochasticity (i.e., decision variability) that better resembled the adjustment to volatility made by the optimal RL agent. Although heightened stochasticity in the volatile environment led participants to more often trial different responses that facilitated discovery of changes to the environment, we also found that anxiety impaired this adaptive ability. The finding of heightened stochasticity in volatile environments contradicts expectations that the learning rate is responsible for successful adaptation and motivates future work on the deleterious role that anxiety plays when adolescents manage periods of transition.

Research field(s)
Psychology & Cognitive Sciences

NOMIS Researcher(s)

Published in

January 8, 2025

The mammalian nervous system is impacted by aging. Aging alters brain architecture, is associated with molecular damage, and can manifest with cognitive and motor deficits that diminish the quality of life. Astrocytes are glial cells of the CNS that regulate the development, function, and repair of neural circuits during development and adulthood; however, their functions in aging are less understood. Astrocytes change their transcriptome during aging, with astrocytes in areas such as the cerebellum, the hypothalamus, and white matter-rich regions being the most affected. While numerous studies describe astrocyte transcriptional changes in aging, many questions still remain. For example, how is astrocyte function altered by transcriptional changes that occur during aging? What are the mechanisms promoting astrocyte aged states? How do aged astrocytes impact brain function? This review discusses features of aged astrocytes and their potential triggers and proposes ways in which they may impact brain function and health span.

Research field(s)
Immunology, Neurology & Neurosurgery

NOMIS Researcher(s)

Published in

January 2, 2025

Glacier-fed streams (GFS) feature among Earth’s most extreme aquatic ecosystems marked by pronounced oligotrophy and environmental fluctuations. Microorganisms mainly organize in biofilms within them, but how they cope with such conditions is unknown. Here, leveraging 156 metagenomes from the Vanishing Glaciers project obtained from sediment samples in GFS from 9 mountains ranges, we report thousands of metagenome-assembled genomes (MAGs) encompassing prokaryotes, algae, fungi and viruses, that shed light on biotic interactions within glacier-fed stream biofilms. A total of 2,855 bacterial MAGs were characterized by diverse strategies to exploit inorganic and organic energy sources, in part via functional redundancy and mixotrophy. We show that biofilms probably become more complex and switch from chemoautotrophy to heterotrophy as algal biomass increases in GFS owing to glacier shrinkage. Our MAG compendium sheds light on the success of microbial life in GFS and provides a resource for future research on a microbiome potentially impacted by climate change.

Research field(s)
Biology, Evolutionary Biology

NOMIS Researcher(s)

Published in

January 1, 2025

The rapid melting of mountain glaciers and the vanishing of their streams is emblematic of climate change1,2. Glacier-fed streams (GFSs) are cold, oligotrophic and unstable ecosystems in which life is dominated by microbial biofilms2,3. However, current knowledge on the GFS microbiome is scarce4,5, precluding an understanding of its response to glacier shrinkage. Here, by leveraging metabarcoding and metagenomics, we provide a comprehensive survey of bacteria in the benthic microbiome across 152 GFSs draining the Earth’s major mountain ranges. We find that the GFS bacterial microbiome is taxonomically and functionally distinct from other cryospheric microbiomes. GFS bacteria are diverse, with more than half being specific to a given mountain range, some unique to single GFSs and a few cosmopolitan and abundant. We show how geographic isolation and environmental selection shape their biogeography, which is characterized by distinct compositional patterns between mountain ranges and hemispheres. Phylogenetic analyses furthermore uncovered microdiverse clades resulting from environmental selection, probably promoting functional resilience and contributing to GFS bacterial biodiversity and biogeography. Climate-induced glacier shrinkage puts this unique microbiome at risk. Our study provides a global reference for future climate-change microbiology studies on the vanishing GFS ecosystem.

Research field(s)
Biology, Evolutionary Biology

NOMIS Researcher(s)

December 20, 2024

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups. The group identified key challenges to paediatric critical care research, including lower patient numbers than for adult critical care, heterogeneity related to cognitive development, comorbidities and illness or injury, consent challenges, disproportionately little research funding for paediatric critical care, and poor infrastructure in resource-limited settings. A seven-point roadmap was proposed: (1) formation of an international paediatric critical care research network; (2) development of a web-based toolkit library to support paediatric critical care trials; (3) establishment of a global paediatric critical care trial repository, including systematic prioritisation of topics and populations for interventional trials; (4) development of a harmonised trial minimum set of trial data elements and data dictionary; (5) building of infrastructure and capability to support platform trials; (6) funder advocacy; and (7) development of a collaborative implementation programme. Implementation of this roadmap will contribute to the successful design and conduct of trials that match the needs of globally diverse paediatric populations.

Research field(s)
Emergency & Critical Care Medicine, Pediatrics

INTRODUCTION: While there may be microbial contributions to Alzheimer’s disease (AD), findings have been inconclusive. We recently reported an AD-associated CD83(+)microglia subtype associated with increased immunoglobulinG4(IgG4) in the transverse colon (TC).

METHODS: We used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.

RESULTS: CD83(+) microglia in the superior frontal gyrus (SFG) are associated with elevated IgG4 and human cytomegalovirus (HCMV) in the TC, anti-HCMV IgG4 in cerebrospinal fluid, and both HCMV and IgG4 in the SFG and vagal nerve. This association was replicated in an independent AD cohort. HCMV-infected cerebral organoids showed accelerated AD pathophysiological features (Aβ42 and pTau-212) and neuronal death.

DISCUSSION: Findings indicate complex, cross-tissue interactions between HCMV and the adaptive immune response associated with CD83(+)microglia in persons with AD. This may indicate an opportunity for antiviral therapy in persons with AD and biomarker evidence of HCMV, IgG4, or CD83(+)microglia.

Research field(s)
Genetics & Heredity, Neurology & Neurosurgery, Biology

NOMIS Researcher(s)

December 18, 2024

Considerable research has shown that people make biased decisions in “optimal stopping problems”, where options are encountered sequentially, and there is no opportunity to recall rejected options or to know upcoming options in advance (e.g. when flat hunting or choosing a spouse). Here, we used computational modelling to identify the mechanisms that best explain decision bias in the context of an especially realistic version of this problem: the full-information problem. We eliminated a number of factors as potential instigators of bias. Then, we examined sequence length and payoff scheme: two manipulations where an optimality model recommends adjusting the sampling rate. Here, participants were more reluctant to increase their sampling rates when it was optimal to do so, leading to increased undersampling bias. Our comparison of several computational models of bias demonstrates that many participants maintain these relatively low sampling rates because of suboptimally pessimistic expectations about the quality of future options (i.e. a mis-specified prior distribution). These results support a new theory about how humans solve full information problems. Understanding the causes of decision error could enhance how we conduct real world sequential searches for options, for example how online shopping or dating applications present options to users.

Research field(s)
Behavioral Science & Comparative Psychology

NOMIS Researcher(s)

Published in

December 18, 2024

A central question in neuroscience is how synaptic plasticity shapes the feature selectivity of neurons in behaving animals1. Hippocampal CA1 pyramidal neurons display one of the most striking forms of feature selectivity by forming spatially and contextually selective receptive fields called place fields, which serve as a model for studying the synaptic basis of learning and memory. Various forms of synaptic plasticity have been proposed as cellular substrates for the emergence of place fields. However, despite decades of work, our understanding of how synaptic plasticity underlies place-field formation and memory encoding remains limited, largely due to a shortage of tools and technical challenges associated with the visualization of synaptic plasticity at the single-neuron resolution in awake behaving animals. To address this, we developed an all-optical approach to monitor the spatiotemporal tuning and synaptic weight changes of dendritic spines before and after the induction of a place field in single CA1 pyramidal neurons during spatial navigation. We identified a temporally asymmetric synaptic plasticity kernel resulting from bidirectional modifications of synaptic weights around the induction of a place field. Our work identified compartment-specific differences in the magnitude and temporal expression of synaptic plasticity between basal dendrites and oblique dendrites. Our results provide experimental evidence linking synaptic plasticity to the rapid emergence of spatial selectivity in hippocampal neurons, a critical prerequisite for episodic memory.

Research field(s)
Neuroscience

Published in

December 18, 2024

Old age is associated with a decline in cognitive function and an increase in neurodegenerative disease risk1. Brain ageing is complex and is accompanied by many cellular changes2. Furthermore, the influence that aged cells have on neighbouring cells and how this contributes to tissue decline is unknown. More generally, the tools to systematically address this question in ageing tissues have not yet been developed. Here we generate a spatially resolved single-cell transcriptomics brain atlas of 4.2 million cells from 20 distinct ages across the adult lifespan and across two rejuvenating interventions—exercise and partial reprogramming. We build spatial ageing clocks, machine learning models trained on this spatial transcriptomics atlas, to identify spatial and cell-type-specific transcriptomic fingerprints of ageing, rejuvenation and disease, including for rare cell types. Using spatial ageing clocks and deep learning, we find that T cells, which increasingly infiltrate the brain with age, have a marked pro-ageing proximity effect on neighbouring cells. Surprisingly, neural stem cells have a strong pro-rejuvenating proximity effect on neighbouring cells. We also identify potential mediators of the pro-ageing effect of T cells and the pro-rejuvenating effect of neural stem cells on their neighbours. These results suggest that rare cell types can have a potent influence on their neighbours and could be targeted to counter tissue ageing. Spatial ageing clocks represent a useful tool for studying cell–cell interactions in spatial contexts and should allow scalable assessment of the efficacy of interventions for ageing and disease.

Research field(s)
Bioinformatics, Biochemistry & Molecular Biology, Immunology, Neurology & Neurosurgery

NOMIS Researcher(s)

Published in

December 11, 2024

SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes. Similar distribution patterns of the spike protein were observed in SARS-CoV-2-infected mice. Injection of spike protein alone was sufficient to induce neuroinflammation, proteome changes in the skull-meninges-brain axis, anxiety-like behavior, and exacerbated outcomes in mouse models of stroke and traumatic brain injury. Vaccination reduced but did not eliminate spike protein accumulation after infection in mice. Our findings suggest persistent spike protein at the brain borders may contribute to lasting neurological sequelae of COVID-19.

Research field(s)
Molecular Biology, Virology, Immunology

NOMIS Researcher(s)

December 4, 2024

Arrayed CRISPR libraries extend the scope of gene-perturbation screens to non-selectable cell phenotypes. However, library generation requires assembling thousands of vectors expressing single-guide RNAs (sgRNAs). Here, by leveraging massively parallel plasmid-cloning methodology, we show that arrayed libraries can be constructed for the genome-wide ablation (19,936 plasmids) of human protein-coding genes and for their activation and epigenetic silencing (22,442 plasmids), with each plasmid encoding an array of four non-overlapping sgRNAs designed to tolerate most human DNA polymorphisms. The quadruple-sgRNA libraries yielded high perturbation efficacies in deletion (75–99%) and silencing (76–92%) experiments and substantial fold changes in activation experiments. Moreover, an arrayed activation screen of 1,634 human transcription factors uncovered 11 novel regulators of the cellular prion protein PrPC, screening with a pooled version of the ablation library led to the identification of 5 novel modifiers of autophagy that otherwise went undetected, and ‘post-pooling’ individually produced lentiviruses eliminated template-switching artefacts and enhanced the performance of pooled screens for epigenetic silencing. Quadruple-sgRNA arrayed libraries are a powerful and versatile resource for targeted genome-wide perturbations.

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

NOMIS Researcher(s)

Published in

November 27, 2024

The DNA-PKcs inhibitor AZD7648 enhances CRISPR–Cas9-directed homology-directed repair efficiencies, with potential for clinical utility, but its possible on-target consequences are unknown. We found that genome editing with AZD7648 causes frequent kilobase-scale and megabase-scale deletions, chromosome arm loss and translocations. These large-scale chromosomal alterations evade detection through typical genome editing assays, prompting caution in deploying AZD7648 and reinforcing the need to investigate multiple types of potential editing outcomes.

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