Research
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NOMIS Research Projects

NOMIS research grants support unconventional research projects led by researchers who have demonstrated exceptional scientific capabilities and leadership. The grants enable scientists to spearhead pioneering research to answer bold questions and advance yet unexplored approaches across scientific and academic disciplines. We award research grants to investigators with an excellent track record in leading groundbreaking, high-risk basic research.

NOMIS Researcher(s)

NOMIS Project 2024

The Question

A first line of defense against pathogens, innate immunity is essential for life, providing an immediate but nonspecific response through physical barriers, immune cells and various proteins. It recognizes and responds to a broad range of microbial threats using pattern recognition receptors to detect conserved pathogen-associated molecular patterns.

This complex response demands precision. The activity of innate immune signaling must be properly regulated to orchestrate a transient and balanced response. Errors in controlling innate immunity can lead to disease: Inflammation caused by the aberrant activity of innate immune receptors is now being viewed as a major driver of several human diseases as well as natural aging. But the exact functioning of the innate immune response is still not fully understood.

“My inspiration to pursue basic research stems from a combination of curiosity, a passion for discovery, and the desire to contribute to the foundational understanding of biological phenomena.”

—Andrea Ablasser

The Approach

The Exploring Innate Immune (In)activities project aims to systemically study molecular checkpoints that control innate immune function. Using an interdisciplinary approach, the researchers seek to identify allosteric sequence motifs within immune receptors and signaling proteins that limit overall activity and control the strength, duration and resolution of immune responses. They will use a combination of structural biology, in silico protein prediction algorithms, biochemistry, and cellular assays to establish a mechanistic understanding of allosteric control at a given site and will classify via in-depth phenotypic analyses in cells and in vivo their impact on cell state and tissue inflammation. The project seeks to generate insights into the rules that govern the functioning of innate immunity and to establish the landscape of the regulatory, evolutionary and therapeutic potential of immune signaling pathways.

Exploring Innate Immune (In)activities is being led by Andrea Ablasser at the Swiss Federal Institute of Technology in Lausanne (EPFL; Switzerland).

Feature image: Airyscan imaging of innate immune stimulated HeLa cells with the nucleus marked in blue.

The Question

Messenger RNAs (mRNA) were discovered in the mid-20th century as molecules that copy the genetic information from DNA in the cell nucleus and carry it to the cytoplasm for protein synthesis. Even today, mRNAs are depicted as simple, short linear chains of nucleotides. Yet, this is misleading, as it does not convey the considerable physical length of these nucleic acid polymers, their propensity to fold, and their existence within diverse and variable protein coatings.

Over the course of its life cycle, every mRNA within eukaryotic cells assembles a complex and dynamic protein coating. These supramolecular assemblies, called messenger ribonucleoproteins (mRNPs), protect the integrity of the mRNA, aid in transport and control the spatiotemporal translation into protein. This is especially important in neurons, in which the unique morphology requires that specific mRNAs travel to the most extreme ends of the cells, the axon terminals, for local translation at the synapses. This spatial choreography supplies the synaptic structures with the proteins needed to sustain the signal that directs activities such as proper brain development or storing memories. Despite their importance in gene expression processes, and in contrast to other classes of RNPs such as ribosomes and spliceosomes, the makeup and transformations of individual mRNPs remain a mystery.

“Understanding the architectural principles of mRNA particles will inform us how the fragile genetic information carrier, mRNA, can safely traverse the crowded and extensive cellular environment of neuronal cells, ensuring that precise protein synthesis occurs only upon reaching the correct location.”

—Elena Conti

The Approach

The research project Visualizing the Messenger: Deciphering the Architecture of Neuronal mRNA Particles at the Atomic Level aims to discern the structure and biochemical nature of mRNPs in the brain throughout the mRNA life cycle. Recent breakthroughs in ad hoc biochemical approaches pioneered by the Conti research group have minimized issues with mRNP fragility and variability, allowing for the isolation of endogenous intact mRNPs.

The project will employ genetic editing to enable strategic molecular cloning in a scalable platform with human induced pluripotent stem cells to extract and analyze large quantities of physiological assemblies in their entirety. The researchers will characterize the protein and mRNA content of selected mRNP targets and study their intra- and intermolecular interactions using mass spectrometry and RNA sequencing. The structural organization of the mRNPs will be determined through cryogenic electron microscopy and electron tomography, aided by computational approaches. Elucidating the structure of these mRNPs will provide insights into the mechanisms with which they function in neuronal processes and will facilitate a molecular understanding of how mutations in mRNP components lead to neurological diseases.

The Visualizing the Messenger project is being led by Elena Conti at the Max Planck Institute of Biochemistry (MPIB) in Munich, Germany.

Feature image: Structural basis for the assembly and recognition of modules in mRNA ribonucleoproteins (mRNPs). 

The Question

How do human beings’ experience of pictures, such as individual artworks or cultural styles of pictorial representation, shape the ways in which people see the natural and social world beyond pictures? Understanding this experience has the potential to impact fields ranging from education and clinical psychology to social behavior and ethics, marking a significant shift in how we understand the relationship between pictorial art and visual perception.

It has been argued that things in the world — objects and states of affair — come to resemble pictures of them that people have already seen in the past. Objects, then, become partly “depictured”: A real landscape might become Cézannesque when shaped by one’s viewing of pictures of Provence by Paul Cézanne; a real cityscape might look Mondrianesque if one has been affected by Piet Mondrian’s abstract figurations of New York City. This concept has radical implications for models of perception and cognition, as well as for theories of aesthetics and representation. But it has rarely been stated systematically by art historians, though it is implied throughout their work — some of the best accounts come from art critics, such as Daniel-Henry Kahnweiler (who promoted Cubism), and writers such as Marcel Proust.

“If pictures change the way we naturally perceive the world around us, then many educational and other implications arise. As individuals, we benefit from being explicit about the visual assumptions we’re always making, often unaware of their origins in pictures we’ve seen. Collectively, when we try to recognize other people’s points of view — as a matter of social and moral responsibility — we’re possibly partly recognizing their pictorial experiences. Therefore, understanding their pictures is a crucial way of understanding their identities.”

— Whitney Davis

The Approach

The project Depictured Worlds: The Perceptual Power of Pictures will study “depicturation” from several points of view. The Depictured Worlds research team will identify likely art-historical cases of depicturation in the history of modern Western arts in their global dissemination, and build additional examples from indigenous, ancient, and/or non-Western arts. By conducting interviews with experts, the researchers will obtain perspectives from human evolution and prehistory, perceptual and cognitive psychology, and sociological and anthropological studies of visual culture. They also will investigate topics including the global dissemination of picture making in prehistory, the historical consequences of schematic and naturalistic styles of depiction, and the variety of social expectations for the perceptual power of pictures.

The project aims to provide a critical history of the concept of depicturation, to assess its usefulness in and implications for disciplines of visual studies in the widest sense, and to explore theoretical models and empirical investigations that might clarify it analytically and test it experimentally. Considering that the perceptual experiences of long-ago populations are not directly accessible, the researchers will explore algorithmic and/or computational approaches that might model complex processes of depicturation in a population.

Depictured Worlds is being led by Whitney Davis at the University of California, Berkeley (US).

Feature image: Brush-and-ink painting of the Derwentwater, England, by Chiang Yee, c. 1925. The art historian E. H. Gombrich used Chiang Yee’s pictures to argue that his perception of landmarks in Britain was shaped by his Chinese training. Is this reasonable?

What can we learn from art and architecture? How do buildings and artworks relate to and create connections with their surroundings? Sites are seen as intersecting and overlapping zones of historically sedimented as well as current and emerging factors. Focusing on selected works and projects in art and architecture since the 1970s, the research project Site Complexes: Models of Responsive Practices for the 21st Century aims to describe and evaluate the transformation of sites performed by specific artworks and architectures through the unfolding of this complex of conditions.

Site Complexes is exploring the processes by which the works, designs and buildings connect the set of conditions that determine their sites to an only partially defined future. These processes are models of responsive practices that do not attempt to adapt a site to predefined principles but rather react to and learn from its complexity. The researchers are investigating these processes as different ways of dealing responsibly with ecological, social, infrastructural and other layers that define a shared reality.

Based on the detailed descriptive recording of the selected objects and processes—what has happened, what is happening, when and where—the team is highlighting the specific methods and techniques of artistic and architectural intervention. The research aims to demonstrate the model character of the singular cases that form the project’s material and thus to detect and demonstrate patterns of an organized interplay between site-conditioning and site-transforming factors, which can be compared with each other. The individual studies, developed in constant collaboration, will thus establish a typology of site complexes and of their “responsible” artistic and architectural transformation.

This typology serves to communicate the research team’s findings in the interdisciplinary exchange of art and architecture as well as in public discourse on the qualities of future developments. Contributing basic research on the concept and concrete procedures of site-responsive practices, the project seeks to encourage dialogue across disciplines, including sociology, urban studies/urban anthropology, environmental sciences, human geography and postcolonial studies, as well as fields of practice, such as cultural heritage, materials research and redevelopment issues. Site Complexes is exploring the possibilities for a responsible coexistence on our ever-changing planet.

Site Complexes: Models of Responsive Practices for the 21st Century is being led by Sebastian Egenhofer at the University of Vienna, Austria, and Stefan Neuner and Susanne Hauser at the Berlin University of the Arts, Germany.

Francesco Petrarca’s Canzoniere, a collection of 366 poems written in 14th century Italy, is arguably the most influential book of love poetry ever written. Known as the “Father of Humanism,” Petrarca popularized the sonnet form, which traveled across Europe and beyond in centuries to come. The cultural, religious and aesthetic assumptions behind the poems did not always adapt themselves easily to foreign tongues and traditions, and the ways in which Petrarch’s poems entered into both European and non-European contexts has created some of the most interesting and complex love literature across the globe.

Petrarch in Global Translation: A Genealogy of Western Love is a collaborative humanities project across languages and national borders that is investigating the foundational conception of Western love as codified by Canzoniere. The project is exploring, for example, the extent to which Petrarchan norms are useful and adaptive models outside of Western contexts. By re-engaging the practice of Petrarchism, which has spawned centuries of literary production and critical reception, Petrarch in Global Translation proposes a simultaneously theoretical and experimental, historical and systematic approach to identifying the dominant “poetics of love” in the Western tradition.

Using the central tool of translation, Petrarch in Global Translation will develop an innovative global approach to Petrarchan poetry as a grammar of love. An initial team of 12 collaborators from countries across Europe as well as the US, Argentina, Iran, China and Japan will translate the same group of Petrarch’s poems from Italian into their respective languages to create a shared textual corpus for subsequent investigations.

The Petrarch in Global Translation project is being led by Ramie Targoff at Brandeis University in Waltham, MA, US, and Judith Frömmer at the University of Vienna, Austria.

Groups of people often encounter difficulties when working together. In many situations, people prioritize their self-interest, which can undermine efforts to benefit the group as a whole, as seen in problems like traffic congestion, public-health failures and climate change. Even when individuals want to act for others, they may struggle to find the best course of action when confronted with social dilemmas where the interests of the individual and the group are not aligned.

The Addressing Collective Action Problems With Machine Intelligence project aims to explore how machine intelligence can help address these challenges in human collective action. While people currently use AI mainly for individual convenience and self-interest, collective-action theory suggests that machine intelligence optimized for public goods may require a different design concept than those intended for individual goods. The project seeks to identify the differences and clarify how social interactions and technology can work together to foster the emergence of social order. It focuses on how this process relates to collective action and the resolution of social dilemmas.

The Addressing Collective Action Problems project will develop and conduct controlled experiments in which many human participants interact with each other with and without the support of machine intelligence in specific social contexts, such as online messaging and driving coordination. The experimental findings will be verified through empirical studies on real-world AI applications. Ultimately, the project aims to demonstrate how machine intelligence can be used as a tool for social interventions that translate knowledge of computer science and AI into helpful practices for public goods.

The project is being led by Hirokazu Shirado at Carnegie Mellon University (Pittsburgh, US).

NOMIS Researcher(s)

NOMIS Project 2023

— 2028

What makes our species unique? The answer to this fundamental question must ultimately lie in our genome, and specifically in genetic changes found only in present-day humans and differing from the genome sequences of Neandertals and Denisovans, the closest evolutionary relatives of present-day humans. Genome comparisons have revealed some 35,000 such sequence changes, but the far greater challenge is to identify which of these genetic differences had truly functional consequences. The project A Molecular View of Human Uniqueness aims to answer this key question.

Using information from Neandertal DNA fragments carried by present-day people, the research team will perform functional analysis of the differences that are likely to have affected metabolism and brain function in modern humans as well as the changes that are specific to Neandertals and Denisovans. This work will contribute to our understanding of the biological functions that distinguish modern humans from their closest evolutionary relatives.

The Molecular View of Human Uniqueness research project is being led by Svante Pääbo at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, in collaboration with the Okinawa Institute of Science and Technology in Okinawa, Japan.

NOMIS Researcher(s)

NOMIS Project 2023

— 2028

Are people a threat to nature, or are they part of nature? Are the natural environment and its objects valuable primarily because they are essential for human survival, or are they valuable in and of themselves? These questions have occupied environmental ethicists for decades, but they also are relevant in a practical context: To develop visions for a sustainable future in Western societies.

The Beyond Intrinsic and Instrumental project combines environmental philosophy with methods from the social sciences to connect ethical arguments for nature’s consideration with the actual human–nature interactions that shape people’s lives. The empirical (social science) aspect of the project aims to achieve a better understanding of what “nature” means to members of different social and professional groups in industrialized countries. What do they value in nature? How and why do they value it? And what norms do they themselves follow in their interactions with nature? In a previous project, the researchers analyzed the values and nature concepts of mountain farmers and identified meaningful interactions with domesticated and wild animals as well as landscapes. The Beyond Intrinsic project focuses on bird watchers as a group with a different—leisure-based—relationship to nature.

As part of the philosophical branch of the project, the team will develop relational arguments for the protection of nature. The reasoning is based on the assumption that respect for nature can take different forms, ranging from the human withdrawal from ecosystems to considerate interaction with natural processes to support for threatened nature and restoration of destroyed nature. Interviews with mountain farmers and bird watchers as groups that have close relations with nature provide examples for how people can and do interact with nature. These data serve as a starting point for the more general philosophical discussion. The researchers are using the concept of relational value as the value that people assign to natural objects in particular human–nature relationships to connect their empirical work with their philosophical arguments. Ultimately, the project will generate proposals regarding what can and should be a sustainable place for humans in nature in Western societies of the Anthropocene.

Anna Deplazes Zemp is leading the Beyond Intrinsic and Instrumental project at the University of Zurich, Zurich, Switzerland. The project is also being supported by the University Research Priority Programme on Global Change and Biodiversity and the UZH Foundation.

NOMIS Researcher(s)

NOMIS Project 2023

— 2028

Aging is the main risk factor for diseases, including neurodegenerative and cardiovascular diseases. In many cases, the effect of aging on different organs is synchronized. Interestingly, aging can be slowed or even reversed by specific interventions, including diet. There also exist suspended animation states—for example, hibernation or diapause—that synchronously pause organ deterioration. But the mechanisms that synchronize organs during aging are unknown. The Organ Synchronization in Aging and Suspended Animation project aims to discover how organs in the body are synchronized during aging.

One of the greatest challenges in studying aging is the long lifespan and expensive nature of traditional experimental model organisms. The Brunet lab has thus developed a powerful platform of genome editing tools in a new model for aging research, the African killifish, a vertebrate with a naturally compressed lifespan of only four to six months. Importantly, the killifish recapitulates typical age-dependent phenotypes and pathologies, notably neurodegeneration with age. The killifish also has a suspended animation state in embryos called diapause, which preserves fully formed organs for long periods of time.

The scalable platform developed by the Brunet lab will be used in killifish to understand the mechanisms underlying synchronization between different organs and how this is affected during aging and suspended animation. The Brunet lab is particularly interested in the role of the specific organs (for example, the brain) as “control centers” for other organs. This knowledge could be game changing for the discovery of key organ–organ communication systems.

Combining the new model organism, unbiased genomics approaches and the power of artificial intelligence, the research project is an innovative investigation into aging and suspended animation. This research has important implications for preserving tissues for long periods of time and countering age-related diseases.

The Organ Synchronization in Aging and Suspended Animation project is being led by Anne Brunet at Stanford University (US).

NOMIS Researcher(s)

NOMIS Project 2023

— 2028

Despite widespread popular and academic concern that artificial intelligence (AI) and robotics are ushering in a jobless future, the industrialized world is currently awash in jobs. The challenge that workers face is not job quantity but rather job quality. Middle-skilled workers without college degrees are increasingly relegated into low-paid, in-person service work that offers little opportunity for developing skills or increasing income—even as highly paid, highly skilled specialties comprise a growing proportion of all work. Recent AI breakthroughs may intensify or, more plausibly, reshape these secular forces, creating an urgent need to understand the relationship between technology and expertise.

The project Will New Technologies Complement or Commodify Expertise? seeks to understand how emerging innovations—especially AI—could change the demand for labor by increasing the value of expertise (for example, by creating new types of skilled work or extending the reach of existing expertise) or reducing the value of skills (and undermining pay) even if jobs are not actually lost. It is exploring these impacts both for workers who use these technologies and for the labor market as a whole, inclusive of those indirectly affected. Using historical and current data, as well as field experiments in collaboration with the developer of a large language model (LLM) and a large online skills marketplace, the researchers are pursuing four main questions:

1) By how much have automation innovations (substituting for workers’ inputs) accelerated relative to augmentation innovations (complementing workers’ outputs), and for which skill groups?

2) Is this acceleration explained primarily by technological fundamentals, by incentives or by both? Can those incentives be shaped to speed augmentation as well as automation?

3) How do the productivity and employment impacts of augmentation innovations and automation innovations differ?

4) How will generative AI affect the value of expertise at scale?

The project will harness and, in some cases, develop disparate data sources, including representative US Census Bureau data as well as newly digitized historical data and industry-level productivity data. It will also launch an ambitious field experiment studying the use of generative AI for work tasks, performed in conjunction with both an online skills marketplace and the developer of a large language model. This research will inform efforts to shape technology to complement rather than undermine the value of labor, potentially helping to buttress the quality—not simply the quantity—of available jobs.

The Expertise project is being led by David Autor at MIT (Massachusetts Institute of Technology) in Cambridge, US.

NOMIS Researcher(s)

NOMIS Project 2023

— 2028

For the first nine months of our lives, we had an essential, physical connection to our mothers. We were free-floating for the first eight days, and then we implanted in the uterus. This was a very difficult transition: Failure to implant accounts for up to 60% of pregnancy losses. Yet, little is known about this stage of development because, by its very nature, the embryo is inaccessible to observation during this time. Illuminating the journey from a fertilized single cell to a complex structure with multiple cell types is essential to understanding the beginning of life and discovering how this journey sets the stage for proper development. It will lead to potential clinical interventions for many diseases, from developmental disorders to infertility.

The project Opening the Black Box of Human Implantation will build upon two previous breakthroughs made by the project’s researchers: culturing natural mammalian embryos through implantation stages in a dish and generating synthetic mouse embryos from embryonic and extra-embryonic stem cells. The researchers will explore how the first cell fate decisions are made in natural human embryos by determining how the genome and transcriptome change from pre- to post-implantation in culture. This will enable them to build the first synthetic human implantation embryo model from stem cells. Using this model, they can study how the body plan is determined, employing approaches that are impossible at these stages with natural human embryos, such as CRISPR-Cas9 gene editing. The researchers will also generate endometrial organoids to recreate the lining of the uterus and build a new maternal implantation niche in vitro. Together, these systems will make possible the investigation of crucial but unknown crosstalk at the maternal–fetal interface and between the emerging embryonic lineages that is essential for successful development and pregnancy.

The researchers anticipate generating combined endometrial–embryo cultures that will support the development of human embryos within a maternal implantation niche, until the anterior–posterior axis first forms. They aim to uncover the signaling, transcriptomic, epigenomic and mechanical determinants of cell fate until the emergence of the organism’s body plan at gastrulation. This research will recreate and reveal a period of human development that has been entirely inaccessible, enabling the investigators to discover the key pathways and events that govern its success or failure.

The Opening the Black Box project is being led by Magdalena Zernicka-Goetz at the California Institute of Technology (Caltech; US) and the University of Cambridge (UK).

What is the nature of mutations underlying phenotypic evolution? In addition to genetic modifications of preexisting genes that can lead to differences in their sequences or activities, the “birth” of new genes with novel functions significantly contributed to the evolution of species-specific traits. The de novo emergence of protein-coding genes—that is, their origination “from scratch” (from previously noncoding DNA sequences)—represents a particularly intriguing mechanism of new gene origination. However, this mechanism was long considered to be highly unlikely, and its prevalence and evolutionary relevance remain poorly understood.

The project De Novo Gene Birth and the Evolution of the Human Brain aims to close this critical gap by systematically tracing and characterizing de novo genes that contributed to the evolution of a key organ that changed in profound ways on the human lineage and defines our species: The brain. Specifically, the investigators seek to unravel the contribution of de novo genes to the evolutionary expansion and elaboration of the neocortex, the seat of higher cognitive functions in humans. The research focuses on the contribution of de novo genes to evolutionary changes of developmental processes—key drivers of phenotypic innovations, given that adult organ anatomies and functions are set up during development.

The De Novo Gene Birth project will generate and analyze translatome data across a unique set of prenatal developmental tissue samples, and experimentally characterize select de novo genes in state-of-the-art in vitro organoid systems, ex vivo fetal tissue cultures and in vivo transgenic mouse models. Ultimately, the researchers hope to illuminate the prevalence and functional roles of de novo genes in primate cortical development and shed light on the molecular evolution underlying the unique biology of our brain.

The project is being led by Henrik Kaessmann at Heidelberg University in Germany.

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.