Insight
is our reward
Search

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.

Docking a flexible basket onto the core of the nuclear pore complex

NOMIS Researcher(s)

Published in

August 13, 2024

The nuclear basket attaches to the nucleoplasmic side of the nuclear pore complex (NPC), coupling transcription to mRNA quality control and export. The basket expands the functional repertoire of a subset of NPCs in Saccharomyces cerevisiae by drawing a unique RNA/protein interactome. Yet, how the basket docks onto the NPC core remains unknown. By integrating AlphaFold-based interaction screens, electron microscopy and membrane-templated reconstitution, we uncovered a membrane-anchored tripartite junction between basket and NPC core. The basket subunit Nup60 harbours three adjacent short linear motifs, which connect Mlp1, a parallel homodimer consisting of coiled-coil segments interrupted by flexible hinges, and the Nup85 subunit of the Y-complex. We reconstituted the Y-complex•Nup60•Mlp1 assembly on a synthetic membrane and validated the protein interfaces in vivo. Here we explain how a short linear motif-based protein junction can substantially reshape NPC structure and function, advancing our understanding of compositional and conformational NPC heterogeneity.

Research field(s)
Biochemistry & Molecular Biology, Biology

DOI
10.1038/s41556-024-01484-x

Removal of TREX1 activity enhances CRISPR–Cas9-mediated homologous recombination

NOMIS Researcher(s)

Published in

August 12, 2024

CRISPR–Cas9-mediated homology-directed repair (HDR) can introduce desired mutations at targeted genomic sites, but achieving high efficiencies is a major hurdle in many cell types, including cells deficient in DNA repair activity. In this study, we used genome-wide screening in Fanconi anemia patient lymphoblastic cell lines to uncover suppressors of CRISPR–Cas9-mediated HDR. We found that a single exonuclease, TREX1, reduces HDR efficiency when the repair template is a single-stranded or linearized double-stranded DNA. TREX1 expression serves as a biomarker for CRISPR–Cas9-mediated HDR in that the high TREX1 expression present in many different cell types (such as U2OS, Jurkat, MDA-MB-231 and primary T cells as well as hematopoietic stem and progenitor cells) predicts poor HDR. Here we demonstrate rescue of HDR efficiency (ranging from two-fold to eight-fold improvement) either by TREX1 knockout or by the use of single-stranded DNA templates chemically protected from TREX1 activity. Our data explain why some cell types are easier to edit than others and indicate routes for increasing CRISPR–Cas9-mediated HDR in TREX1-expressing contexts.

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

DOI
10.1038/s41587-024-02356-3

A gate tunable transmon qubit in planar Ge

NOMIS Researcher(s)

Published in

July 30, 2024

Gate-tunable transmons (gatemons) employing semiconductor Josephson junctions have recently emerged as building blocks for hybrid quantum circuits. In this study, we present a gatemon fabricated in planar Germanium. We induce superconductivity in a two-dimensional hole gas by evaporating aluminum atop a thin spacer, which separates the superconductor from the Ge quantum well. The Josephson junction is then integrated into an Xmon circuit and capacitively coupled to a transmission line resonator. We showcase the qubit tunability in a broad frequency range with resonator and two-tone spectroscopy. Time-domain characterizations reveal energy relaxation and coherence times up to 75 ns. Our results, combined with the recent advances in the spin qubit field, pave the way towards novel hybrid and protected qubits in a group IV, CMOS-compatible material.

Research field(s)
Josephson Junctions, Qubits

DOI
10.1038/s41467-024-50763-6

The peripheral interior and people as infrastructure: adopting the sewer system for passage

NOMIS Researcher(s)

Published in

July 29, 2024

During the Warsaw Uprising of 1944, soldiers and civilians used the city’s sewer system to move from place to place and to pass objects and information. Although many who entered the underground did not survive its conditions, the adoption of the sewer as a passage for people did save thousands of lives. Drawing on technical materials and testimonies of the survivors, the article examines this appropriation of the sewer system, concentrating on the way it functioned. It explicates how the reliance of the sewer’s adoption on the engagement of people turned them and their bodies into infrastructure, and how it led to augmenting the ontology of the sewer. The article offers a new interpretation of the Warsaw sewer appropriation and enriches the conceptual framework by bridging infrastructural notions with the periphery-centre concepts. Moreover, it advances research on ‘periphery’ by, firstly, counteracting the underrepresented and peripheral status of Eastern Europe in architectural history and, secondly, validating infrastructural spaces and broadening the scope of spaces included as interiors frequented by people. The paper also contributes to scholarship on spaces experienced largely through non-visual sensory modalities, an understudied area of architectural history due to the discipline’s rootedness in the domain of sight.

Research field(s)
Architecture

DOI
10.1080/13602365.2024.2370284

CCAR1 promotes DNA repair via alternative splicing

NOMIS Researcher(s)

Published in

July 25, 2024

DNA repair is directly performed by hundreds of core factors and indirectly regulated by thousands of others. We massively expanded a CRISPR inhibition and Cas9-editing screening system to discover factors indirectly modulating homology-directed repair (HDR) in the context of ∼18,000 individual gene knockdowns. We focused on CCAR1, a poorly understood gene that we found the depletion of reduced both HDR and interstrand crosslink repair, phenocopying the loss of the Fanconi anemia pathway. CCAR1 loss abrogated FANCA protein without substantial reduction in the level of its mRNA or that of other FA genes. We instead found that CCAR1 prevents inclusion of a poison exon in FANCA. Transcriptomic analysis revealed that the CCAR1 splicing modulatory activity is not limited to FANCA, and it instead regulates widespread changes in alternative splicing that would damage coding sequences in mouse and human cells. CCAR1 therefore has an unanticipated function as a splicing fidelity factor.

Research field(s)
Genetics & Heredity, Biomedical Research

DOI
10.1016/j.molcel.2024.06.011

Thresholds for adding degraded tropical forest to the conservation estate

NOMIS Researcher(s)

Published in

July 17, 2024

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2,3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (<29% biomass removal) retain high conservation value and a largely intact functional composition, and are therefore likely to recover their pre-logging values if allowed to undergo natural regeneration. Second, the most extreme impacts occur in heavily degraded forests with more than two-thirds (>68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked.

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

DOI
10.1038/s41586-024-07657-w

Moving beyond stewardship to partnership with nature: how Swiss alpine farmers’ relationships to nature and relational values are co-constituted

NOMIS Researcher(s)

Published in

July 15, 2024

Ecologically considerate use of nature (including agriculture) has often been associated with ‘stewardship’ as a human-nature relationship which involves human care, responsibility and accountability and is thus more sustainable than the alternative human-nature relationship of manager of nature. We show that the consideration of nature in agriculture can go further than stewardship by presenting data from qualitative interviews with Swiss Alpine farmers indicating that many of them view their relationship with nature as a form of partnership. Drawing on literature of human-nature partnership, we characterize this relationship by 1) bidirectionality – a give and take between nature and humans–, 2) the understanding of nature as a subject rather than an object and 3) interaction with nature that consists of collaboration rather than giving commands. The mountain farmers expressed all of these features in their farming practices and descriptions of their role in nature. A few farmers even saw their role as subordinates to nature, for which we introduced the new human-nature relationship category of “apprenticeship”. We further suggest that the partnership relation between humans and nature in many respects shares key features with relational values, for instance in its non-centric nature and in its emphasis of the combination of benefits for people with care for nature. In that sense, we aim at combining different accounts of inclusive, non-dichotomous and context-sensitive dealings with nature and we suggest that this combination is applicable also to contexts beyond agriculture.

Research field(s)
Philosophy

DOI
10.1080/26395916.2024.2374757

Deep 3D histology powered by tissue clearing, omics and AI

NOMIS Researcher(s)

Published in

July 12, 2024

To comprehensively understand tissue and organism physiology and pathophysiology, it is essential to create complete three-dimensional (3D) cellular maps. These maps require structural data, such as the 3D configuration and positioning of tissues and cells, and molecular data on the constitution of each cell, spanning from the DNA sequence to protein expression. While single-cell transcriptomics is illuminating the cellular and molecular diversity across species and tissues, the 3D spatial context of these molecular data is often overlooked. Here, I discuss emerging 3D tissue histology techniques that add the missing third spatial dimension to biomedical research. Through innovations in tissue-clearing chemistry, labeling and volumetric imaging that enhance 3D reconstructions and their synergy with molecular techniques, these technologies will provide detailed blueprints of entire organs or organisms at the cellular level. Machine learning, especially deep learning, will be essential for extracting meaningful insights from the vast data. Further development of integrated structural, molecular and computational methods will unlock the full potential of next-generation 3D histology.

Research field(s)
Biochemistry & Molecular Biology, Chemistry

DOI
10.1038/s41592-024-02327-1

Single cell transcriptomes and multiscale networks from persons with and without Alzheimer’s disease

NOMIS Researcher(s)

Published in

July 10, 2024

The emergence of single nucleus RNA sequencing (snRNA-seq) offers to revolutionize the study of Alzheimer’s disease (AD). Integration with complementary multiomics data such as genetics, proteomics and clinical data provides powerful opportunities to link cell subpopulations and molecular networks with a broader disease-relevant context. We report snRNA-seq profiles from superior frontal gyrus samples from 101 well characterized subjects from the Banner Brain and Body Donation Program in combination with whole genome sequences. We report findings that link common AD risk variants with CR1 expression in oligodendrocytes as well as alterations in hematological parameters. We observed an AD-associated CD83(+) microglial subtype with unique molecular networks and which is associated with immunoglobulin IgG4 production in the transverse colon. Our major observations were replicated in two additional, independent snRNA-seq data sets. These findings illustrate the power of multi-tissue molecular profiling to contextualize snRNA-seq brain transcriptomics and reveal disease biology.

Research field(s)
Genetics & Heredity, Biology

DOI
10.1038/s41467-024-49790-0

FilamentID reveals the composition and function of metabolic enzyme polymers during gametogenesis

NOMIS Researcher(s)

Published in

June 20, 2024

Gamete formation and subsequent offspring development often involve extended phases of suspended cellular development or even dormancy. How cells adapt to recover and resume growth remains poorly understood. Here, we visualized budding yeast cells undergoing meiosis by cryo-electron tomography (cryoET) and discovered elaborate filamentous assemblies decorating the nucleus, cytoplasm, and mitochondria. To determine filament composition, we developed a “filament identification” (FilamentID) workflow that combines multiscale cryoET/cryo-electron microscopy (cryoEM) analyses of partially lysed cells or organelles. FilamentID identified the mitochondrial filaments as being composed of the conserved aldehyde dehydrogenase Ald4ALDH2 and the nucleoplasmic/cytoplasmic filaments as consisting of acetyl-coenzyme A (CoA) synthetase Acs1ACSS2. Structural characterization further revealed the mechanism underlying polymerization and enabled us to genetically perturb filament formation. Acs1 polymerization facilitates the recovery of chronologically aged spores and, more generally, the cell cycle re-entry of starved cells. FilamentID is broadly applicable to characterize filaments of unknown identity in diverse cellular contexts.

Research field(s)
Microbiology, Biology

DOI
10.1016/j.cell.2024.04.026

Waves of regulated protein expression and phosphorylation rewire the proteome to drive gametogenesis in budding yeast

NOMIS Researcher(s)

Published in

June 20, 2024

Sexually reproducing eukaryotes employ a developmentally regulated cell division program—meiosis—to generate haploid gametes from diploid germ cells. To understand how gametes arise, we generated a proteomic census encompassing the entire meiotic program of budding yeast. We found that concerted waves of protein expression and phosphorylation modify nearly all cellular pathways to support meiotic entry, meiotic progression, and gamete morphogenesis. Leveraging this comprehensive resource, we pinpointed dynamic changes in mitochondrial components and showed that phosphorylation of the FoF1-ATP synthase complex is required for efficient gametogenesis. Furthermore, using cryoET as an orthogonal approach to visualize mitochondria, we uncovered highly ordered filament arrays of Ald4ALDH2, a conserved aldehyde dehydrogenase that is highly expressed and phosphorylated during meiosis. Notably, phosphorylation-resistant mutants failed to accumulate filaments, suggesting that phosphorylation regulates context-specific Ald4ALDH2 polymerization. Overall, this proteomic census constitutes a broad resource to guide the exploration of the unique sequence of events underpinning gametogenesis.

Research field(s)
Biology

DOI
10.1016/j.devcel.2024.05.025

APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer’s Disease

NOMIS Researcher(s)

Published in

June 19, 2024

Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer’s disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer’s disease caused by the PSEN1E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant (APOE3Ch). Heterozygosity for the APOE3Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1E280A variant is prevalent.

Research field(s)
Health Sciences, Genetics & Heredity, Clinical Medicine

DOI
10.1056/NEJMoa2308583

Geometry-driven migration efficiency of autonomous epithelial cell clusters

NOMIS Researcher(s)

Published in

June 19, 2024

The directed migration of epithelial cell collectives through coordinated movements plays a crucial role in various physiological processes and is increasingly understood at the level of large confluent monolayers. However, numerous processes rely on the migration of small groups of polarized epithelial clusters in complex environments, and their responses to external geometries remain poorly understood. To address this, we cultivate primary epithelial keratocyte tissues on adhesive microstripes to create autonomous epithelial clusters with well-defined geometries. We show that their migration efficiency is strongly influenced by the contact geometry and the orientation of cell–cell contacts with respect to the direction of migration. A combination of velocity and polarity alignment with contact regulation of locomotion in an active matter model captures quantitatively the experimental data. Furthermore, we predict that this combination of rules enables efficient navigation in complex geometries, which we confirm experimentally. Altogether, our findings provide a conceptual framework for extracting the interaction rules of active systems from their interaction with physical boundaries, as well as design principles for collective navigation in complex microenvironments.

Research field(s)
Biophysics

DOI
10.1038/s41567-024-02532-x

Information content and optimization of self-organized developmental systems

NOMIS Researcher(s)

Published in

May 31, 2024

A key feature of many developmental systems is their ability to self-organize spatial patterns of functionally distinct cell fates. To ensure proper biological function, such patterns must be established reproducibly, by controlling and even harnessing intrinsic and extrinsic fluctuations. While the relevant molecular processes are increasingly well understood, we lack a principled framework to quantify the performance of such stochastic self-organizing systems. To that end, we introduce an information-theoretic measure for self-organized fate specification during embryonic development. We show that the proposed measure assesses the total information content of fate patterns and decomposes it into interpretable contributions corresponding to the positional and correlational information. By optimizing the proposed measure, our framework provides a normative theory for developmental circuits, which we demonstrate on lateral inhibition, cell type proportioning, and reaction–diffusion models of self-organization. This paves a way toward a classification of developmental systems based on a common information-theoretic language, thereby organizing the zoo of implicated chemical and mechanical signaling processes.

Research field(s)
Biology

DOI
10.1073/pnas.232232612

Evolution of diapause in the African turquoise killifish by remodeling the ancient gene regulatory landscape

NOMIS Researcher(s)

Published in

May 28, 2024

Suspended animation states allow organisms to survive extreme environments. The African turquoise killifish has evolved diapause as a form of suspended development to survive a complete drought. However, the mechanisms underlying the evolution of extreme survival states are unknown. To understand diapause evolution, we performed integrative multi-omics (gene expression, chromatin accessibility, and lipidomics) in the embryos of multiple killifish species. We find that diapause evolved by a recent remodeling of regulatory elements at very ancient gene duplicates (paralogs) present in all vertebrates. CRISPR-Cas9-based perturbations identify the transcription factors REST/NRSF and FOXOs as critical for the diapause gene expression program, including genes involved in lipid metabolism. Indeed, diapause shows a distinct lipid profile, with an increase in triglycerides with very-long-chain fatty acids. Our work suggests a mechanism for the evolution of complex adaptations and offers strategies to promote long-term survival by activating suspended animation programs in other species.

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

DOI
10.1016/j.cell.2024.04.048

The first two blastomeres contribute unequally to the human embryo

NOMIS Researcher(s)

Published in

May 13, 2024

Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to the 2-cell stage embryo. However, whether and how such clonal asymmetries arise in the embryo is unclear. Here, we performed prospective lineage tracing of human embryos using live imaging, non-invasive cell labeling, and computational predictions to determine the contribution of each 2-cell stage blastomere to the epiblast (body), hypoblast (yolk sac), and trophectoderm (placenta). We show that the majority of epiblast cells originate from only one blastomere of the 2-cell stage embryo. We observe that only one to three cells become internalized at the 8-to-16-cell stage transition. Moreover, these internalized cells are more frequently derived from the first cell to divide at the 2-cell stage. We propose that cell division dynamics and a cell internalization bottleneck in the early embryo establish asymmetry in the clonal composition of the future human body.

Research field(s)
Biology

DOI
10.1016/j.cell.2024.04.029

Proximity-induced gapless superconductivity in two-dimensional Rashba semiconductor in magnetic field

NOMIS Researcher(s)

Published in

May 1, 2024

Two-dimensional semiconductor-superconductor heterostructures form the foundation of numerous nanoscale physical systems. However, measuring the properties of such heterostructures, and characterizing the semiconductor in-situ is challenging. A recent experimental study by [Phys. Rev. Lett. 128, 107701 (2022)] was able to probe the semiconductor within the heterostructure using microwave measurements of the superfluid density. This work revealed a rapid depletion of superfluid density in semiconductor, caused by the in-plane magnetic field which in presence of spin-orbit coupling creates so-called Bogoliubov Fermi surfaces. The experimental work used a simplified theoretical model that neglected the presence of non-magnetic disorder in the semiconductor, hence describing the data only qualitatively. Motivated by experiments, we introduce a theoretical model describing a disordered semiconductor with strong spin-orbit coupling that is proximitized by a superconductor. Our model provides specific predictions for the density of states and superfluid density. Presence of disorder leads to the emergence of a gapless superconducting phase, that may be viewed as a manifestation of Bogoliubov Fermi surface. When applied to real experimental data, our model showcases excellent quantitative agreement, enabling the extraction of material parameters such as mean free path and mobility, and estimating g-tensor after taking into account the orbital contribution of magnetic field. Our model can be used to probe in-situ parameters of other superconductor-semiconductor heterostructures and can be further extended to give access to transport properties.

Research field(s)
Quantum

DOI
10.21468/SciPostPhys.16.5.115

Lifelong persistence of nuclear RNAs in the mouse brain

NOMIS Researcher(s)

Published in

April 4, 2024

Genomic DNA that resides in the nuclei of mammalian neurons can be as old as the organism itself. The life span of nuclear RNAs, which are critical for proper chromatin architecture and transcription regulation, has not been determined in adult tissues. In this work, we identified and characterized nuclear RNAs that do not turn over for at least 2 years in a subset of postnatally born cells in the mouse brain. These long-lived RNAs were stably retained in nuclei in a neural cell type–specific manner and were required for the maintenance of heterochromatin. Thus, the life span of neural cells may depend on both the molecular longevity of DNA for the storage of genetic information and also the extreme stability of RNA for the functional organization of chromatin.

Research field(s)
Genetics & Heredity, Biology

DOI
10.1126/science.adf3481

Load More
  • NOMIS Foundation 2025
  • 2025 NOMIS Foundation