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Funding
Funding
HFSP supports novel, innovative and interdisciplinary basic research focused on the complex mechanisms of living organisms. A clear emphasis is placed on novel collaborations that bring biologists together to focus on problems at the frontier of the life sciences.
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Awardees
Awardees
In this section you find information about the awardees in the HFSP scientific programs. This includes a searchable database of HFSP awardees, information on the HFSP Nakasone Award and other achievements by HFSP awardees.
- News & Impact
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Events
Events
HFSP promotes and participates in several events every year. We are committed to bringing together the scientific community and forging new opportunities to network and have scientific discussions that help to create bridges and partnerships for the future of frontier science.
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About
About
The Human Frontier Science Program is a program of funding for frontier research in the life sciences. It is implemented by the International Human Frontier Science Program Organization (HFSPO) with its office in Strasbourg. Here you can find all you need to know about the HFSPO.
Awardees
2025
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Grant Awardees - Program Grants
Harmony in Dynamics: Exploring Emergent Cooperation through Participatory Art and Neuroscience
HERSHBERG Uri (United States)
- University of Haifa - Haifa - ISRAEL
PERONDI Luciano (ITALY)
- Università Iuav di Venezia - Venezia - ITALY
AYAZ Hasan (United States)
- Drexel University - Philadelphia - United States
People behave in unique and individual ways, yet when they come together in shared environments, groups emerge that exhibit consistent and predictable behaviors. Whether it’s navigating a busy market, generating an immune response, or participating in rush-hour traffic, the individual actions of people or cells lead to stable patterns of group behavior. These group behaviors emerge naturally, without requiring centralized control, and adapt as situations change. But how do such predictable patterns arise from diverse and independent behaviors? Our project aims to explore this question by using Ta, a participatory art piece, as a controlled experiment to study how stable groups form from individual actions. In Ta, participants sit around a table in front of several piles of pebbles and follow simple rules to manipulate the pebbles. Without speaking or directly communicating, participants begin by moving pebbles in their own ways, but over time, their actions synchronize, and a collective pattern of pebble movement emerges. This dynamic but stable group behavior provides a model for understanding how group dynamics arise in the real world. What makes this experiment unique is the use of an evolving art piece as our model. While Ta is an artificial environment, it mimics the complexity of natural settings in ways that engage participants. The collaboration with Ta's creator, Goni Shifron, is essential to ensure that the art piece continues to evolve and reflect the complexity needed for meaningful study. To study Ta, we will use cutting-edge tools to capture and analyze real-time motion, brain activity, physiology, and eye movements of the participants. By combining expertise in complex systems, interactive design, and neuroscience, we aim to identify patterns of change and synchronization in both the participants' actions and the movement of the pebbles. Through this innovative approach, we hope to uncover the underlying principles that explain how individual behaviors lead to the formation of cohesive and stable group dynamics.
2025
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Grant Awardees - Program Grants
Eyes inside out: Visual coding without a multilayered retina in squid and worms
BADEN Tom (GERMANY)
- The University of Sussex - Brighton - United Kingdom
BOK Michael (United States)
- Lund University (Lunds universitet) - Lund - SWEDEN
“Camera-type” eyes like ours represent perhaps the most fascinating and recognisable of all sensory systems. They are found across the animal kingdom, from spiders to eagles, or even some clams. Looking at these eyes’ external similarities immediately suggests that they must share a common origin. However, nothing could be further from the truth! Instead, these eyes evolved independently, possibly more than 100 times in different living and extinct lineages. In nearly all cases, these eyes have remained tiny, but at least three times in the evolutionary history, they have gotten large: In vertebrates such as ourselves, in cephalopods such as octopus or squid, and in one obscure group of worms: The alciopids, a group of segmented worms akin to earthworms that live in the open ocean. Inside each of these eyes is a retina – a thin sheet of light sensitive tissue that represents the first neuronal step of vision. In vertebrates, the retina is made up of many dozens of anatomically and functionally distinct neuronal cell types, each with a specific and fascinating job in shaping the way that we see. This diversity is thought to be fundamental to allowing our eyes to perform efficiently. Like a “mini-computer” right in the eyeball, the vertebrate retina preprocesses and compresses the image as it comes in, such that the central brain can predominately worry about ‘what to do’ with the information. This process is incredibly efficient, and probably enables much of what we call ‘vision’ in the first place. By contrast, a vertebrate-like neurally diverse retina is absent in cephalopods and alciopids. Instead, each photoreceptor – essentially a ‘pixel’ - immediately sends its signal to the brain. This suggests that vertebrate-like preprocessing of the incoming information does not take place. How, then, do these animals see? Do they ‘simply dump’ the corresponding information straight into the brain (implying very different central processing strategies compared to our own), or do they have unique ‘tricks’ to deal with the problem? Furthermore, did cephalopods and alciopids independently arrive at the same set of tricks? This project brings together a ‘computational neuroscientist’ and ‘behavioural marine biologist’ to jointly establish how the retinas of these alien eyes work, how they evolved, and how their strategies for vision relate to our own.
2025
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Grant Awardees - Early Career
Sub-second dopamine dynamics in human basal ganglia during beat perception and rhythmic action
CANNON Jonathan (United States)
- McMaster University - Hamilton - CANADA
BANG Dan (DENMARK)
- Aarhus University (Aarhus Universitet, AU) - Aarhus - DENMARK
When we listen to danceable music, we quickly feel the underlying beat. The beat makes us want to move along, and when we do, we find that we can step or bob our head in precise anticipation of the rhythmic sounds. Evolutionarily, our sense of rhythm has been linked to adaptations that have made the human lineage uniquely successful, including language and upright walking. How does the human brain make these moment-by-moment sound predictions, and why is auditory rhythm so closely connected with body movement? We believe that a key piece of this puzzle is the chemical messenger dopamine. Dopamine levels in a deep brain area called the “basal ganglia” are understood to play an important role in our capacity to make, evaluate, and learn from predictions; they are also believed to be important in motivating and selecting bodily actions. Until now, we have not had the methods to directly investigate the relationship between dopamine and the human sense of rhythm. Our team has developed mathematical models describing how dopamine supports our perception of rhythm and rhythmic movements. We will now test the model predictions using a cutting-edge method for measuring how dopamine levels change moment-by-moment in the basal ganglia of patients who are undergoing awake brain surgery as part of their treatment. During the recordings, the patients, who volunteer to participate in the research, will listen to and tap along with different rhythms. We will analyze the relationships between rhythms, movements, and dopamine, and compare what we see to what our models predicted. The results will help us develop models that more accurately describe dopamine’s role in human rhythm and in the brain at large. Our project will deepen our understanding of the biological basis of rhythm, central to music, dance, speech and many other human activities. It will also provide general insights about dopamine, which may help us better understand dopamine-related disorders like Parkinson’s disease and how best to treat them.
2025
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Grant Awardees - Program Grants
Behavioral adaptation to arsenic-rich environments
BARGMANN Cornelia (United States)
- The Rockefeller University - New York - United States
NEW Elizabeth (AUSTRALIA)
- The University of Sydney - Sydney - AUSTRALIA
SHINYA Ryoji (JAPAN)
- Meiji University - Kawasaki - JAPAN
BRAENDLE Christian (SWITZERLAND)
- Centre National de la Recherche Scientifique Délégation Côte d'Azur - Nice - FRANCE
Climate change is an ongoing threat to the humans, plants, and animals that must adapt to newly inhospitable environments. One underappreciated aspect of this threat is the degradation of groundwater and lakes by the accumulation of toxic elements like arsenic that can cause neuronal damage and death. The resulting mineral-extreme environments are increasing worldwide— for example, over 200 million people are currently exposed to toxic levels of arsenic in their drinking water. To inspire better strategies for detoxification and resilience, we will study animals that can naturally thrive in these arsenic-extreme environments. Our studies will first focus on a nematode worm species that we recently isolated from Mono Lake, an arsenic-extreme natural lake that is incompatible with most animal life. This Mono Lake nematode is highly resistant to arsenic and has behavioral and lifestyle adaptations that promote its survival. For example, almost all nematodes reproduce by laying eggs, but this one incubates its offspring inside its body after hatching, providing nutrients to them and birthing progeny once they reach a stress-resistant stage. Unlike the few other animals that live in Mono Lake, our nematode can easily be grown in the lab, so we can study the properties that allow it to survive. We will ask: what behavioral and physiological specializations in these animals promote their survival in harsh conditions? How are those specializations implemented by their neurons, tissues, and genes? We will then examine these properties in other nematodes from a variety of extreme environments to see if they use similar strategies. We are a team of scientists with expertise in nematode biology, ecology, chemistry, genetics, and neuroscience, so we are ready to address each of these questions in detail.
2025
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Grant Awardees - Program Grants
Evolutionary biophysics of spiralian asymmetric divisions
TURLIER Hervé (FRANCE)
- CNRS Délégation Occitanie Ouest - Toulouse - France, Metropolitan
MARTÍN-DURÁN Chema (SPAIN)
- Queen Mary University of London - London - United Kingdom
BARONE Vanessa (ITALY)
- The Board of Trustees of the Leland Stanford Junior University - Pacific Grove - United States
Asymmetric cell divisions, which produce two distinct daughter cells, are crucial for multicellularity as they drive the formation of specialized cell types. Traditionally, these divisions have been associated with changes in the position of the plane that separates the mother cell into two daughters. However, many marine invertebrates employ a different strategy to create cellular asymmetries right after fertilization: they form a cellular protrusion known as the \"polar lobe,\" which is inherited by only one daughter cell, leading to a distinct developmental fate. Interestingly, this evolutionary innovation has independently arisen in multiple species, making it an ideal system for studying the origins of asymmetric divisions in evolution. Key questions arise: How did polar lobes evolve? Do all embryos with polar lobes rely on similar mechanisms? How predictable is evolution when similar solutions emerge independently in different species? To address these fundamental questions, we are bringing together three cross-disciplinary teams with expertise in evolutionary, developmental, and cell biology, as well as cell mechanics, bioinformatics, biophysics, and computational modeling. Focusing on up to 12 non-model marine invertebrates, we will leverage the work of evolution to explore these mechanisms by: 1) using evolutionary developmental biology (evo-devo) and comparative omics to identify the molecules responsible for polar lobe formation and segregation; 2) employing live imaging and biophysics to dissect the cytoskeletal dynamics that generate polar lobes; and 3) applying theoretical and computational modeling to replicate and interrogate the physical mechanisms underlying asymmetric divisions. Our collaboration will reveal how cellular mechanics and developmental genetics interact to generate asymmetries and novel structures during animal embryogenesis. This research will open new avenues at the intersection of biophysics and evolutionary biology, transforming the rich diversity of marine invertebrates into a powerful system for investigating fundamental biological questions with potential insights extending to other animals, including humans.
2025
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Grant Awardees - Program Grants
Growth rate control in methanotrophs: engineering a biological sink for atmospheric methane
HAURYLIUK Vasili (SWEDEN)
- Lund University (Lunds universitet) - Lund - SWEDEN
TVEIT Alexander Tøsdal (NORWAY)
- UiT The Arctic University of Norway - Tromsø - NORWAY
BASAN Markus (United States)
- President and Fellows of Harvard College, Harvard Medical School - Boston - United States
Global warming is an immanent treat to humanity. One of the drivers behind this process is the accumulation of atmospheric methane, a powerful greenhouse gas. Biological capture of methane is a promising approach that could help redress the situation and counter the climate change. The biggest biological sink of methane is its consumption by atmospheric methane oxidizing bacteria (atmMOB). These microorganisms can live on a unique ‘diet’ of methane from air as energy and carbon source. Despite their planetary importance of atmMOBs, we know precious little about these unique bacteria. This is because until very recently it was impossible to growth them in the laboratory. In 2019, this major obstacle was overcome by the team of Alexander Tveit at the University of Tromsø. This breakthrough lays the foundation for the current project, allowing us to understand how atmMOB sense the environment and convert atmospheric methane into biomass. The key aspect of bacterial macroeconomics of growth is the cellular investment of the metabolic resources into production of the ribosomes, the universal molecular machines the synthesise proteins in all the living cells. Decades of research on model organisms such as Escherichia coli have established that the faster bacteria grow, the more ribosomes they need. However, little is known about the laws governing the growth of atmMOB. In this project we seek answers to the following questions: How do bacteria that live off air coordinate their growth? How do they sense when they are ‘hungry’ to control their ribosome production? Can we exploit our understanding of atmMOB growth laws to engineer faster growing strains for efficient methane capture? To do so, we have assembled an international consortium bringing together expertise in atmMOB microbiology (Alexander Tveit), protein synthesis and ribosomes (Vasili Hauryliuk) and bacterial growth laws (Markus Basan).
2025
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Grant Awardees - Program Grants
Molecular memories in single cells: An integrated approach to how cells learn
BHAMLA Saad (United States)
- University of Colorado Boulder - Boulder - United States
DUSSUTOUR Audrey (FRANCE)
- CNRS DR14 - Toulouse - FRANCE
CHEN Wanze (CHINA)
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences - Shenzhen - CHINA
It has long been thought that memories are stored in the brain by strengthening the connections between neurons. However, recent discoveries suggest that molecules inside cells, especially RNA, might also be involved in storing and transferring memories. Our project explores this idea by studying a free-swimming organism called Spirostomum ambiguum and immune cells known as macrophages. These single cells are capable of learning from their experiences, much like more complex organisms. For example, they can \"train\" themselves to respond more effectively to challenges they’ve faced before. A key tool in our research is Live-seq, a cutting-edge technology that allows us to study the activity of individual cells over time without killing them. Traditional methods for studying cells typically destroy the cell during analysis, limiting what we can learn. Live-seq, however, enables us to track gene activity in living cells, making it possible to see how a cell’s behavior and gene expression change as it \"learns.\" We are particularly interested in how cells can exhibit associative memory—a form of learning similar to how Pavlov’s dogs learned to associate a bell with food. In cells, this could mean \"remembering\" a previous stimulus and preparing a stronger response the next time. Additionally, we will explore the possibility of implanting synthetic or \"false\" memories into cells by transferring RNA from one cell to another, potentially demonstrating that RNA can carry memory-specific information. This research could change how we understand memory in all living organisms and might even lead to new medical applications, such as improved treatments for immune-related diseases.
2025
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Grant Awardees - Early Career
Coordination of Cell Consortia via Soluble Factors
BLAESCHKE Franziska (GERMANY)
- German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) - Heidelberg - GERMANY
HICKEY John (United States)
- Duke University - Durham - United States
ROVIRA CLAVE Xavier (SPAIN)
- Fundacio Institut de Bioenginyeria de Catalunya (Institute for Bioengineering of Catalonia) - Barcelona - United States
Individual cells self-organize within our bodies to build the tissues and organs that enable life. We know that soluble molecules, like cytokines, chemokines, and growth factors, contribute to guiding cells into specific arrangements. While we know that sometimes one of these factors can direct a cell to perform a specific task, most bodily functions and diseases depend on a complex combination of these factors interacting with each other—often in ways that are not yet predictable. We still do not fully understand how these networks of interacting factors are created and what their function on tissue restructuring is because of limitations with experimental, measurement, and computational approaches. In our project, \"Soluble Factors and Cell Arrangements\" (SOLFEGE), we will develop new approaches that enable us to explore for the first time how networks of soluble factors coordinate the behavior of different cell types. We will develop massive sample and experimental barcoding mixed with advanced imaging and computational approaches to: 1) study how immune cells get organized in tumor organoids exposed to specific soluble factors, 2) use soluble factor-releasing particles to analyze how soluble factors influence cell organization, and 3) uncover how networks of factors released by tumor-specific T cells coordinate cellular processes in the tumor microenvironment. We will combine our unique expertise in advanced tissue imaging, spatial mapping, live tumor models, genetic testing, biomaterials, and computational modeling to decode how these networks function in solid tumors. A better understanding of the interplay between soluble factors and cellular arrangements will not only advance basic scientific knowledge on tissue organization but also pave the way for innovative therapeutic strategies that harness the contributions of soluble factors and the tissue microenvironment.
2025
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Long-Term Fellowships - LTF
Quality control of large membrane protein complexes
BOEGEHOLZ Lena (GERMANY)
. - California Institute of Technology - Pasadena - United States
VOORHEES Rebecca (Host supervisor)
REES Douglas (Host supervisor)
Proteins are molecular machines that are necessary for us and our cells to survive as they are involved in nearly every process in life. For example, they enable uptake and digestion of nutrients, movement or perception of and communication with the environment. For many of these processes, proteins have to work together in large protein complexes to achieve a certain goal. This is comparable to how a car is assembled from multiple parts that all function together. During its lifetime, the protein complex as well the car experience wear and tear that will eventually cause individual parts to break. If the car owner wants to continue driving, either the broken part in the car has to be replaced or they have to buy a new car. Additionally, the damaged piece has to be discarded correctly as a cluttered environment impairs cellular processes comparable to how it is difficult to work in a messy garage. Like the manufacturing of a car, production of proteins is a complicated process that costs a lot of energy and resources. Therefore, the cell aims to maintain a balance between production and degradation of proteins to ensure that there are enough functioning protein complexes to survive without cluttering the cell or tying up too many resources. In this proposal, I am suggesting to study whether individual subunits of a protein complex can be replaced like a broken car part or whether the whole complex has to be exchanged. I will also determine whether damaging different proteins in the same complex can lead to different outcomes. Similarly, some parts in the car, like a broken bulb, can be easily replaced, while other parts like the engine or the car frame might not be worth exchanging. In the latter case, it might be more cost and time efficient to buy a new car. Like the car frame, proteins that will lead to degradation of the whole complex are most likely found in its core and are essential for stability. Furthermore, I will analyze whether specific proteins are needed for the replacement process. While there are general proteins responsible for the degradation of damaged proteins, sometimes specialized factors are necessary for more difficult tasks. This is comparable to the use of a car brand specific tool, when a normal screwdriver is not suited for the repair. After determining the identity of the necessary protein tools, I will analyze how they exert their function to improve understanding of why specialized repair proteins are required. Overall, the proposed study will increase knowledge of how damaged proteins in protein complexes are replaced. I will show whether the cell is able to perform cost effective repairs and which other proteins are necessary for the process.
2025
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Long-Term Fellowships - LTF
Understanding the role of tertiary lymphoid structures in chronic hepatitis C infection
BORRELLI Costanza (ITALY)
. - The Rockefeller University - New York - United States
VICTORA Gabriel (Host supervisor)
Tertiary lymphoid structures (TLS) are immune cell aggregates resembling lymph nodes that form in conditions of chronic inflammation or cancer. Interestingly, tertiary lymphoid structures are widely observed in the clinics, and correlate with detrimental prognosis in autoimmune diseases, COVID infection and transplant patients, but with favorable therapeutic outcomes in several cancer types. While their prognostic value patients is widely recognized, the molecular mechanisms underlying these clinical associations remain elusive. Indeed, little is known about where, why and how TLS form. Most importantly, their immune function and contribution to disease course remain elusive. Here, I propose to study TLS formation and functions in the context of infection with hepatitis C virus (HCV), a virus that affects 1 to 3% of the worldwide population and causes liver damage and hepatocellular carcinoma. TLS are a diagnostic feature of chronic HCV infection, however their role in promoting viral persistence and disease progression is unknown. My aims are to (1) map cellular interactions in TLS arising upon HCV infection, (2) perturb TLS formation in order to functionally evaluate their contribution to disease progression to cirrhosis and hepatocellular carcinoma and (3) track the dynamics of TLS formation and the lymphocyte trafficking to and from these structures. To interrogate the cellular interactions that lead to TLS formation and maturation, this project will combine a mouse model of chronic hepatitis C infection with the LIPSTIC technology, recently conceived in the Victora laboratory. LIPSTIC (Labeling of Immune Partnerships by SorTagging Intercellular Contacts) is a method to study cell-cell interactions in the mouse based on enzymatic transfer of a labeled substrate from one cell to another. Like actual lipstick, this system allows tracking of cellular kiss-and-run events and can be applied to contact-trace immune and non-immune cells. Once identified, the cellular interactions occurring in the liver during hepatitis C infection will be tested to uncover which ones are promoting or suppressing formation of TLS. We will further track the trafficking of cells to and from TLS using photoconversion, a technique that allows to color cells at specific locations by shining a light on them. Cells can then be followed as they travel through the body. Finally, we will generate a mouse model in which TLS formation and location can be visualized in living mice, allowing for monitoring of these structures over time and greatly reducing the number of animals used for this study. This project, which leverages my expertise in in vivo screening in the liver and the Victora lab’s expertise in recording lymphocyte interactions and dynamics, will yield insights into the cellular events leading to TLS formation and maturation upon hepatitis C virus infection, with unprecedented resolution. It will further our knowledge of TLS function and uncover their role in regulating disease progression and tumorigenesis. Furthermore, it will generate tools to study TLS biology in other pathological settings such as infections by respiratory viruses, autoimmune diseases and cancer.
2025
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Cross Disciplinary Fellowships - CDF
Epitranscriptome profiling in the DepMap: An engine for target and biomarker discovery in cancer
CHAN Chi Kong (Hong Kong (China))
. - Massachusetts Institute of Technology - MIT - Cambridge - United States
DEDON Peter (Host supervisor)
Cancer is one of the top threats to human health and a leading cause of death worldwide, taking away ~10 million lives each year. While significant progress has been made in understanding many aspects of cancer biology, the intricacy of how cancer arises, progresses, and interacts with the body remains inconclusive. Further research is essential for making breakthroughs in diagnosis, treatment, and cure. Emerging evidence has now linked cancer development with defects in the process that makes proteins, i.e., translation, and the levels of key cancer-driving proteins. However, little is known about the precise mechanisms causing these defects. This project is dedicated to providing new insights into the mechanisms that drive cancer development and progression, thus revealing novel diagnostic biomarkers for cancer types and potential targets for anticancer drug development. Here, I propose to expand my toolbox and learn an innovative platform of systems-level technologies to explore defects in the translation process across 50 Cancer Dependency Map (DepMap) cell lines from 5 tumor types (lung, glioblastoma, kidney, colon, and breast cancers; 10 cell lines each). This research is crucial because it has the potential to transform cancer biology by opening the door to systematic determination of the degree of dysfunction in the translation process in human cancers. This approach could also be useful for the study of over 100 other human diseases that have been connected with defects in translation. After completing all the cell analyses, I will learn and perform data processing, data mining, programming, and machine learning to comprehend the findings and identify patterns and signatures in the data. These signatures could be unique to each cancer type and useful for further development as diagnostic tools and therapeutic targets. Our team of experts in systems biology, computational biology, and cancer biology will also collaborate with leading medical institutions to extend the studies to dozens of human sarcoma samples to assess whether similar mechanisms and signatures can also be applied to clinical samples. Not only will this research add new and original knowledge about a frontier area of cancer biology, with creation of a database of defects in the translation process in cancer, but the results will also identify novel potential targets for drug discovery and development as well as the predictive power of the identified signatures for cancer type, prognosis, and drug sensitivity.
2025
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Long-Term Fellowships - LTF
Shedding light on rhodopsin-mediated microbial phototrophy at the single-cell level
CHAZAN Ariel (Israel/Poland)
. - Swiss Federal Institute of Technology in Zurich (ETH Zurich/ETH Zürich) - Zurich - SWITZERLAND
STOCKER Roman (Host supervisor)
Sunlight is a crucial energy source that drives the functioning of aquatic environments. At the core of these ecosystems are phototrophic microbes—tiny organisms that “capture” sunlight and convert it into biochemical energy to support their metabolic needs. This vital process, known as light harvesting, is central to aquatic food webs, enabling microbes to funnel energy into the microbial community. Phototrophic microbes use specialized protein complexes to absorb light energy, initiating a series of chemical reactions that culminate in the production of adenosine tri-phosphate (ATP), a molecule commonly referred to as the universal energy currency of most organisms. Only two types of protein complexes are known to govern this capture of sunlight energy by microbes. One major group of microbes uses a form of chlorophyll to perform photosynthesis in a manner similar to plants. This process is well understood and plays a significant role in shaping microbial communities. However, during the past two decades, discoveries hint at another significant player in these light-harvesting processes: rhodopsin-bearing microbes. These microbes use the rhodopsin protein to pump protons (H+) across their membrane to generate a proton gradient, which is used to produce ATP molecules. Rhodopsin-bearing microbes are tremendously abundant in aquatic environments and can constitute more than half of the microbial population in marine and freshwater ecosystems. They may therefore represent a major source of energy entering microbial communities. However, due to a lack of sensitive methods to measure light harvesting mediated by rhodopsins, we know very little about their ecological contribution. Understanding how much light is captured by rhodopsin-bearing microbes will allow us to measure their ecological impact and offer insights into their roles in the flow of energy and elements in aquatic environments. This project is dedicated to developing tools to explore the contribution and impact of rhodopsin-bearing microbes to microbial light harvesting. The main aim of this project is to develop innovative measurement techniques to investigate how these microbes contribute to light-energy acquisition. We will develop cutting-edge technology to measure light-harvesting at the single microbe level, and to sort those microbes for identification and further analysis. Exploring the contribution of individual microbes is critical to understanding the role of different microbial species, which can vary across time and environments. This project will result in a deeper understanding of the fundamental process of light harvesting and its impact on aquatic microbial populations. This project aims to bring the ecological contribution of rhodopsin-bearing microbes to light harvesting out from the shadows and into the scientific spotlight. By uncovering their ecological significance and providing novel tools to measure their impact, this research holds the potential to make a significant contribution to our understanding of microbial ecosystems.
2025
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Long-Term Fellowships - LTF
Artificial selection and the rapid evolution of a plant-viral mutualism
CHEN Jason (USA/Canada)
. - Netherlands Institute of Ecology (NIOO-KNAW) - Wageningen - NETHERLANDS
ZWART Mark (Host supervisor)
In Darwin’s tangled bank, organisms of different species make their living not only by exploiting, but also by cooperating with each other. Many species interactions are ecologically specialized, with partners engaging in cooperative and exploitative relationships with just a few other species, and evolving remarkable adaptations which they rely on to maintain those associations. However, these specialized interactions can also evolve in different ways, with parasitic interactions evolving into mutualistic interactions and vice versa, sometimes with surprising rapidity. This is particularly common in host-microbe interactions, in which microbes can rapidly evolve to become either pathogenic or beneficial for plants and animals. In the early 17th century, parts of Dutch society were transfixed by “tulip mania”, a cultural and financial craze over this exotic bulb that had been recently imported from the Ottoman empire. Driving this fad, in part, were tulips that spontaneously and unpredictably sported delicately feathered, multicolored streaks and spots in their flowers, which could not be inherited by seed and was associated with a gradual decline in plant vigor, making the plants that developed these traits particularly rare and valuable. Today, we know this phenomenon, known as color breaking, is a symptom of infection with a plant virus. Though viral infections weaken tulips and are often fatal, a few cultivars dating back as early as the era of tulip mania survive to this day: They harbor the virus, but nonetheless continue to be cultivated and asexually propagated as rare curiosities for their color-broken flowers. The careful maintenance of these cultivars coexisting with the virus living inside their tissues thus constitutes a possible artificial selection experiment on the evolution of viral mutualism, commencing centuries before viruses were even known to science. As a HSFP fellow, I will ask whether surviving color-broken tulips harbor viral mutualists that rapidly evolved during tulip domestication and breeding in Europe, and examine the genomic and ecological mechanisms underpinning viral mutualism. To do so, I will combine multiple approaches, ranging from the reconstruction of tulip virus evolution to the introduction of mutations into engineered tulip virus genomes. My research will address a fundamental question on the emergence of novel host-microbe mutualisms, which has consequences for our understanding of the ecological role of viruses in natural populations, and more broadly the evolutionary flexibility of host-microbe interactions. Beyond its importance for understanding how we can manipulate viruses to benefit agriculture and horticulture in a model organism of commercial & cultural value, my work also sits at the interface of biology and history, illustrating the role of evolutionary phenomena in shaping human history and culture.
2025
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Long-Term Fellowships - LTF
Phyto-Umwelt: Decoding the Multisensory World of Plants
CHOI Noori (South Korea)
. - University of Canterbury - Christchurch - New Zealand (Aotearoa)
NELSON Ximena (Host supervisor)
STRINGER Lloyd (Host supervisor)
Plants are often thought of as stationary and less responsive than animals, but recent research reveals they are much more perceptive than previously believed. Plants have a sophisticated way of sensing their perceptual world - “phyto-umwelt.” In the phyto-umwelt, plants can detect and react to a variety of signals, such as smells, sounds, and vibrations, which help them interact with and adapt to fluctuating environments in complex ways. This project focuses on understanding how plants perceive and respond to different and complex sensations, using apple trees as a study system. I will examine how apple trees react to environmental changes, such as attacks from herbivores, by integrating information from various sensory inputs, including chemical signals released by nearby plants, vibrations caused by insects, and other stimuli in their phyto-umwelt. By studying these responses, the project aims to uncover how plants have developed these sensory abilities and how they use them to adapt and survive. The research will begin with field studies in apple orchards to collect data on various sensory inputs. For example, plants and insects release chemicals called volatile organic compounds (VOCs) into the air and soil, which can signal different conditions or threats. I will also record environmental sounds and vibrations from the environment and nearby insects. By analyzing this data, I will investigate what apple trees experience in their phyto-umwelt and how these different signals might interact (e.g., buzzing sounds paired with insect-released chemicals). Follow-up lab experiments will investigate how apple saplings respond to these stimuli, using advanced molecular techniques to observe their reactions at the cellular level. In particular, I will investigate whether and how a plant’s response differs when exposed to single versus combined sensory inputs. For instance, saplings may show faster or more specific responses to a combination of signals from herbivorous insects than to just one signal alone. In the next phase, I will test whether a plant's ability to sense multiple signals is influenced by its environment, comparing wild and domesticated apple trees. There has long been a debate about whether domestication weakens plant defenses, but the evidence is mixed. It is possible that domesticated plants, living in controlled environments, have become specialized in responding to fewer types of stimuli, potentially losing their ability to handle a broader range of sensory events (e.g. invasive insects). To study this, I will recreate both natural and controlled environments for apple trees and expose them to various familiar and new stimuli to see how they react. By comparing their responses to familiar and new signals, this research will shed light on how plants adapt their sensory systems over time, especially in environments shaped by humans. The findings could have broader implications beyond plant biology. Understanding how plants process sensory information without a centralized nervous system, like the brain and spine, might offer new insights into information processing in technology, such as artificial intelligence and robotics. Additionally, this research could lead to new strategies for sustainable agriculture by improving plant resistance to pests and environmental stressors. Ultimately, this project could transform our understanding of how living organisms perceive their environment, potentially opening new avenues for research across the life sciences, from the molecular mechanisms of sensory perception to broader ecological and evolutionary contexts.
2025
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Grant Awardees - Program Grants
Neurometabolic mechanisms for social foraging
EL HADY Ahmed (EGYPT)
- University of Konstanz (Universität Konstanz) - Konstanz - GERMANY
FROEMKE Robert (United States)
- NYU Grossman School of Medicine - New York - United States
CHOI Jee Hyun (Korea (South))
- Korea Institute of Science and Technology (KIST) - Seoul - Korea (South)
Animals of all species need to find food in order to survive. Often this is a dangerous and uncertain process, required in order to fulfill their own energetic needs as well as provide for infants or other members of a group or colony. In this project, our team (consisting of scientists from Germany, Korea, and the US) studies how mouse colonies solve this problem in different environmental conditions. Animals must decide when and where to go get the most resources, and decide when to leave resource rich areas to find new ones. Many mammals (including mice and humans) are social foragers, and depend on their social group to help find food or know when resources are being depleted. In this project, we ask how animal groups coordinate their behaviors to achieve a collective goal important for survival of the individuals and the group as a whole. Mice are an ideal species for this project due to the interesting behaviors they perform for cooperating and competing for resources, and the availability of tools for studying brain activity that have been optimized for lab mice. There have also been remarkable advances in machine learning and documentary approaches that enable long-term 24/7 continuous monitoring of mouse life in naturalistic environments. This will allow us for the first time to document strategies and plans by which animals might cooperate or help each other obtain the necessary resources for survival in a dynamic and potentially dangerous world.
2025
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Long-Term Fellowships - LTF
Dissecting bacterial defense to antibiotics
CHOUDHARY Divya (INDIA)
. - President & Fellows of Harvard College - Cambridge - United States
GARNER Ethan (Host supervisor)
PAULSSON Johan (Host supervisor)
Antibiotic resistance is a growing global health crisis, making many bacterial infections harder to treat, leading to millions of deaths annually and threatening the success of routine medical procedures. The rise of resistant bacteria outpaces the development of new antibiotics, highlighting the urgency for improved treatment strategies. One reason for treatment failure is that genetically identical bacteria often react differently to the same antibiotic, where not all bacterial cells succumb; a few tolerant cells regrow, resulting in persistent infections. Understanding why certain bacteria survive antibiotic treatment, while others do not, is crucial for addressing this spreading pandemic of antibiotic resistance. Antibiotics typically target essential bacterial components like the cell membrane, DNA replication, or protein synthesis, which are encoded by essential genes and present in every cell. Thus, these drugs affect all the cells in a population, but not all cells in the population are killed. The underlying cellular mechanisms and behaviors in response to antibiotic treatment that lead to variability in cell death remain poorly understood. Interestingly, the cellular antibiotic response can either allow bacteria to survive or, paradoxically, contribute to cell death. While genetic resistance—which is passed down to subsequent generations—is well-studied, phenotypic resistance—where individual cells temporarily tolerate antibiotics due to environmental factors—is less understood and more challenging to study without advanced techniques. My proposed research aims to fill this gap by examining global gene expression fingerprints at the single bacterial cell resolution to identify key genes that can predict cell survival under antibiotics. Each bacterial genome acts as a codebook for producing thousands of proteins. It is the timing, levels, and lifetime of these proteins that dictate how individual bacteria behave under stress. I will probe the transcription of genes encoding every protein in the bacterial cell to identify the key genes that enable bacterial survival under antibiotics. The three essential developments to assay such a high throughput library include: a) time-lapse imaging to track lineage information b) single cell resolution assay to visualize individual bacteria, and c) high throughout scaling using custom built microscopes and genetic barcoding to assay the whole library in each experiment. This systematic approach will be made possible by harnessing technological advancement in the labs of my mentors – Johan Paulsson and Ethan Garner - at Harvard University and their collaborators. I will use a microfluidic based system with quantitative time-lapse imaging, which allows for the analysis of individual bacteria over many generations. This system has been advanced by my host labs, enabling the tracking of over 1 million bacterial lineages over time in independent growth trenches, which will allow me to capture an entire library of transcriptional reporter strains in an optical-pooled-screen approach, with each growth trench serving as a distinct experiment. By analysing individual lineages using machine learning, I aim to identify candidate genes whose expression differentiates live cells from dead ones under antibiotic treatment. Modulating the levels of protein products of the key genes associated with dead cells will aid in developing strategies to enhance bacterial susceptibility to antibiotics. Additionally, the findings will be applied to multidrug-resistant pathogens to evaluate if similar mechanisms can be targeted to improve treatment efficacy or whether the tolerance mechanisms are pathogen-specific. This project has the potential to make a significant impact beyond antibiotic resistance by offering valuable insights into other fields such as cancer research, immunology, and developmental biology, where understanding variability in cellular responses is vital.
2025
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Long-Term Fellowships - LTF
Investigating CD1a-driven T cell responses to UVB light exposure
CIACCHI Laura (AUSTRALIA)
. - University of Oxford - Oxford - United Kingdom
OGG Graham (Host supervisor)
Ultraviolet light (UV) from direct sun exposure can induce skin inflammation, sunburn and skin cancers in humans. Skin lipids (fats or oils) play an essential role in maintaining skin integrity and barrier function in protecting the body from foreign microbes and from the harmful effects of UV. Here, I hypothesize that natural skin lipids are altered by UV exposure and accumulate in the skin subsequently promoting inflammatory responses via a skin-specific novel (‘CD1’) pathway. Specifically, I will study the role of immune cells (‘T cells’) which are usually involved in the defence against infections, but in some cases can cause excess skin inflammation in chronic conditions such as psoriasis and other diseases. Despite research over many decades, we still know relatively little about why the T cells are active in inflamed skin. The proposed project therefore aims to analyse the T cell pathways driving skin inflammatory responses using high-throughput approaches, with the use of state-of-the-art technologies. Based on the functional and phenotypic readout of these approaches, will enable us to gain fundamental biological insights into alterations in human skin upon UV exposure in skin disease settings. Overall, these proposed studies have the potential to challenge existing ideas of how T cells function and will assess the effect of environmental UV on skin inflammation and disease.
2025
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Long-Term Fellowships - LTF
Characterization of the human Notch-ligand synapse
CURRIE Michael (NEW ZEALAND)
. - President and Fellows of Harvard College, Harvard Medical School - Boston - United States
BLACKLOW Stephen (Host supervisor)
KIRCHHAUSEN Tomas (Host supervisor)
In the human body, large structures such as tissues and organs are formed by the development of specialized structures made up of different types of cells. The cells need to adopt the desired cell identities for their different functions (e.g. muscle or neuron) and need to know when to divide or die. The goal of this project is to visualize a biological process called Notch signaling, which plays an essential role in human development by guiding many of these cell fate decisions. In normal Notch signaling, Delta or Jagged proteins on signal-sending cells bind to and pull on Notch proteins present on signal-receiving cells. By pulling on Notch, Delta or Jagged renders Notch susceptible to precise processing by molecular scissors. The processed Notch then enters the receiver cell nucleus, acting as an effector to stimulate changes in gene expression that specify cell fate. Aberrant Notch signaling, on the other hand, can result in cancer or other diseases. For example, mutations of the human Notch1 protein are causal in more than half of human T-cell acute lymphocytic leukemias. Mutations of human Notch2 or human Jagged1 also cause a devastating developmental disorder called Alagille syndrome that is often lethal at an early age. It has been recently discovered that the Delta and Notch molecules that perform Notch signaling are enriched on the cell surface at the sites of contact between signal-sending and receiving cells. These enriched sites are termed the “Notch synapse”, akin to the synapses that exist between cells in neuronal signaling. These synapses were observed with moderate magnifications that show the process at the cellular level. However, to see the finer details of the interaction at the subcellular level requires much higher magnification using the powerful new tools of electron microscopy. This project thus aims to use electron microscopy to view synapses between Notch and Delta cells at a resolution that can discern the molecular interactions taking place. By imaging the synaptic sites, information will be obtained about the arrangement of cell surface molecules and whether they cluster or use auxiliary systems for stability. The project will also study the role of the cell’s internal framework system, the cytoskeleton, in Notch signaling. The area directly inward from the synapse will be examined to determine the influence of the cell cytoskeleton in creating or maintaining synapses. In other cellular processes, the cytoskeleton is used as a railway network to move cargo around the cell. Lastly, the project aims to move beyond single cell pair interactions to organoid models. Organoids are three-dimensional clusters of cells that can be formed in a laboratory, outside of a host. Under optimized growth conditions, they can be stimulated to mimic human tissues and even the full complexity of an organ. It is not yet known whether Notch synapses form in organoids, and if so the extent of formation, as these cells have much more complex contacts with adjacent cells than the cell pairs. This project thus aims to utilize three avenues of research to increase our understanding of the Notch synapse, ranging from the molecular level to the complexity of an organoid. Because Notch signaling is required for the development and function of many tissues and organs (e.g. heart, brain, muscle, intestine, liver, immune system, etc.), the discoveries we will make in this project will have implications both for many areas of human biology, including developmental biology and immunology, and for the many diseases associated with aberrant Notch signaling, including cardiovascular disease and cancer.
2025
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Grant Awardees - Program Grants
Decoding the evolution of anticipation and decision making in uncertain environments
DAL BELLO Martina (ITALY)
- Yale University - New Haven - United States
GRILLI Jacopo (ITALY)
- The Abdus Salam International Centre for Theoretical Physics - Trieste - ITALY
MCGLYNN Shawn (United States)
- National University Corporation Tokyo Institute of Technology - Tokyo - JP
Every day, we rely on our ability to remember patterns and associations to help us prepare in advance for later events. For example, when we see dark clouds on the horizon, we might expect rain to come. Research has shown that organisms from the microbial world can also develop pattern associations and predictive models that allow them to make preparations in advance for environmental changes. The mechanisms underpinning anticipation involve genome regulation and also individuality between single-cells, where individuals uniquely prepare as future \"pioneers\" to altered conditions. However, only a small number of organisms are typically studied, making it impossible to explain the diversity of strategies observed across the bacterial tree of life. Going further, the mechanisms that microbes might “learn” pattern associations through an evolutionary process are not clear: how much information about environmental dynamics can microbes “remember”? how does this depend on the \"complexity\" of organisms? Getting a deeper understanding of how the level of predictability of the environment has shaped, and continues to shape, ecological and evolutionary processes is of paramount importance as the Earth and its environments continue to change. In this proposal we seek to develop answers to these questions by bringing international expertise in microbial ecology, single-cell resolved views of populations, and evolutionary-information theory. We will grow a diverse pool of microbial species in different environments ranging from steady, to repetitive (for example day/night cycling as we experience ourselves), to random. We will explore how much cells learn in these environments, as a function of their level of predictability, and the possible variables that affect this, for example genome size, and growth rates. To understand the role of individuality, we will make observations of populations at the single-cell level, quantifying individual cell activity by tracking nutrient uptake rates (how much was eaten, and what was eaten). These experimental observations will be interpreted with a mathematical approach which relates learning to environmental information content. Through evolutionary experiments, we will study the limits and mechanisms of anticipation across diverse organisms, allowing us to develop a general understanding of learning in the microbial world.
2025
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Grant Awardees - Program Grants
1+1=1: Bioengineering synthetic symbiosis to illuminate how a microalga becomes an endosymbiont
DECELLE Johan (FRANCE)
- French National Centre for Scientific Research (Centre national de la recherche scientifique,CNRS) - Paris - FRANCE
DUCAT Daniel (United States)
- Michigan State University - East Lansing - United States
KOHLHEYER Dietrich (GERMANY)
- Forschungszentrum Jülich GmbH (Research Center Jülich) - Jülich - GERMANY
Life evolved by multiple symbiotic interactions between merging single-celled organisms that led to acquisition of genes, organelles, and new functionalities. For instance, a symbiosis between a host and intracellular photosynthetic cells (microalgae), called photosymbiosis, occurred several times in the evolution and led to the origin of all the photosynthetic organisms on earth, such as plants, trees and algae. In this process, engulfed photosynthetic cells were gradually transformed into an organelle, called the chloroplast, which produces oxygen and energy with light and feeds earth food webs. Photosymbiosis is still a widespread life strategy in aquatic and terrestrial ecosystems, such as lichens, corals and in the ocean plankton, and plays fundamental ecological roles with economic values. Despite the importance of photosymbiosis in the evolution of life and in ecosystems, we know very little on how the two organisms (host and photosynthetic partners) interact with each other, mainly because they are difficult to maintain and study in the laboratory and there is a lack of high-resolution imaging and genetic tools. How 2 cells become 1 cell (1+1=1) is one of the most intriguing mysteries in life we want to tackle in this project. We propose to create a new photosymbiosis with bioengineered cyanobacteria and a host cell with an interdisciplinary team covering expertise in biology, microfabrication of culture systems, microscopy, and physiology. This will allow us to investigate the fundamental steps of the integration of photosynthetic cells inside a host, and their metabolic responses to the engulfment. At relevant temporal and spatial scales, we will co-culture and scrutinize the two partners in different conditions using genetically-modified cyanobacteria that can perform different functions (excretion of sugars). This ambitious project will address fundamental questions in biology and will provide new knowledge on one of the most important events in the evolution of life.