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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
Exploring Interdisciplinary Frontiers to Understand Tick-Virus Dynamics at a Global Scale
KOTSYFAKIS Michail (GREECE)
- FORTH Institute of Molecular Biology and Biotechnology (IMBB-FORTH) - Heraklion - GREECE
DIABATE Abdoulaye (BURKINA FASO)
- Centre MURAZ-BURKINA FASO - Bobo-Dioulasso - BURKINA FASO
MANS Ben (SOUTH AFRICA)
- Agricultural Research Council - Pretoria - SOUTH AFRICA
KAR Sirri (TURKEY)
- Tekirdag Namik Kemal University - Tekirdag - TURKEY
The spread of diseases transmitted by ticks is becoming an increasing concern globally, especially with the rapid changes to our environment driven by climate change and human activities. The project focuses on the Crimean-Congo Haemorrhagic Fever Virus (CCHFV), a dangerous virus spread by ticks in many regions across Africa, Europe, and Asia. Ticks, particularly those of the Hyalomma species, are the main carriers of this virus. While some regions such as South Africa and parts of Europe are considered hotspots for CCHFV outbreaks, the factors driving the spread of the virus remain poorly understood. The project’s main goal is to better understand how the virus, the ticks that carry it, and the environment interact, so that we can predict and hopefully reduce the viral spread in the future. One area of focus is how Hyalomma marginatum and Hyalomma rufipes—two closely related species of ticks—spread across different habitats. These ticks can be transported long distances by migratory birds, which may help the ticks to cross geographical barriers, bringing them into new areas. The project also aims to investigate whether these tick species are interbreeding, creating hybrids that could alter how the virus is transmitted. By studying the genetics of these ticks across different regions, we will better understand how different tick populations are related and how their movement might be affecting pathogen spread. The team will also study the viruses found in the ticks. We know that ticks can carry several different viruses, and this project will identify which viruses are present in different regions. This will help to determine whether specific tick populations carry more dangerous strains of viruses. The research will look at how environmental factors, such as temperature, humidity, and land use, influence where ticks live and how they spread. This information will help us predict how climate change might affect tick populations and viral transmission in the future. The project is an intercontinental collaboration involving researchers from four countries, who will share their expertise and data to tackle this problem. The findings will help prepare for future disease outbreaks linked to changing environmental conditions. This knowledge will be crucial for public health authorities in planning disease prevention and control strategies in regions at risk.
2025
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Long-Term Fellowships - LTF
Probing the evolutionary structural biology of the centriole using a unique deep-branching protist
EGLIT Yana (Canada/Russia)
. - University of Geneva (Université de Genève) - Geneva - SWITZERLAND
GUICHARD Paul (Host supervisor)
HAMEL Virginie (Host supervisor)
Cells, the basic units of life, come in many shapes and sizes. Whether they're part of larger organisms like plants and animals or exist independently as single-celled organisms, their structure is essential to how they function. A cell's shape and organisation are largely determined by its internal skeleton, called the cytoskeleton. One of the key components of this internal framework is a structure known as microtubules. In most cells, microtubules form the backbone of important extensions called flagella or cilia. Flagella are whip-like structures that enable cell movement, as seen in sperm cells, for example. Cilia, present in nearly all cells, help with sensing the environment and communication between cells. Both flagella and cilia are assembled from a structure called the centriole, which also plays a critical role during cell division, helping ensure that genetic material (DNA) is properly separated and distributed to new cells. While typical animal cells have centrioles and flagella/cilia, many organisms have lost these structures over the course of evolution. Instead, their cytoskeletons are organized around alternative structures, such as those found in cellular slime moulds or yeasts, or through dynamic self-organisation, as seen in plants and many amoebae. The evolutionary origins of these alternative organising centres remain poorly understood. Given that the last common ancestor of all modern eukaryotes was almost certainly capable of forming both flagella and centrioles, organisms with non-centriolar organising centres must have evolved from ancestors that once possessed fully functional centrioles. This raises two questions: Did these organisms simplify their centrioles over time, or did they develop entirely new ways to organise their cells? Answering these questions is crucial as it will deepen our understanding of how life's complexity emerged and evolved. My research aims to address this by studying Meteora sporadica, a recently cultivated single-celled protist with an unusual cellular structure. Meteora moves using long protrusions and features several arm-like extensions that swing back and forth, all supported by bundles of microtubules. These microtubules converge at seven small organising centres that closely resemble parts of centrioles found in other cells. We believe these organising centres may be remnants of centrioles that have evolved over time. Notably, Meteora is closely related to other cells with flagella, which further supports the idea that these organising centres are related to centrioles. To explore this question, we will use cutting-edge imaging techniques to develop detailed models of Meteora’s organising centres. Meteora is an extremely small cell, and its organising centres are smaller than the resolution limit of visible-light microscopy. Therefore, we will use cryo-electron tomography, a revolutionary high-resolution imaging technique used to characterise macromolecular scale structures, to create a model of the organising centres. Moreover, we will search its genome to identify proteins of plausible centriolar origin, and generate antibodies to label these proteins with fluorescent tags. We will then use another advanced technique that bypasses the light resolution limit, called expansion microscopy, to pinpoint the location of these proteins in the cell. By using these state-of-the-art techniques, we aim to unlock the mysteries of Meteora’s organizing centers and illuminate the ancient pathways of evolution that shaped the complexity of life.
2025
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Long-Term Fellowships - LTF
Dissecting brainstem neural circuits orchestrating intra-oral tongue movements
ELTABBAL Mohamed (EGYPT)
. - The Salk Institute for Biological Studies - La Jolla - United States
AZIM Eiman (Host supervisor)
BRAINERD Elizabeth (Host supervisor)
When we chew, speak, or drink our tongue moves precisely inside our mouth. How are these immaculate tongue movements controlled by our brain? Sometimes you bite your tongue or you choke – these unfortunate mishaps are caused by the uncoordinated action of breathing, tongue, and jaw movements. How do breathing and chewing movements coordinate with those of the tongue? To answer these questions, we need to monitor tongue movements with high temporal and spatial precision in animals that provide experimental access to the neural circuits that control these behaviors. Monitoring tongue movements inside the mouth and their precise millisecond coordination with other concomitant motor actions (e.g., breathing and chewing) is challenging. In my proposed project, I propose to integrate micro-X-ray reconstruction of moving morphology (micro-XROMM) with genetic and physiological approaches in mice to dissect, manipulate, and record brainstem neural circuits that control 3D intra-oral tongue movement during natural behaviors like chewing and drinking. Micro-XROMM offers access to detailed intra-oral 3D dynamics and kinematics of the tongue at millisecond temporal and submillimeter spatial resolutions. Moreover, mice offer unparalleled molecular-genetic selectivity for accessing and manipulating specific mammalian neural circuits. By combining these approaches, I aim to characterize the complex motor space of intra-oral tongue movements and how it is coordinated with chewing and breathing at the behavioral level. I will follow this precise behavioral characterization with anatomical and functional dissection of a putative brainstem neural circuit responsible for this coordination. Our work will lay the foundation for exploring the tongue as a unique sensory-motor system. I will introduce a new framework, based on biological insights, to model the circuit-level control of fine-scale complex dynamics of flexible elastic bodies using the tongue as a model, with implications that extend well beyond neuroscience and clinical medicine to soft robotics and continuum mechanics.
2025
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Long-Term Fellowships - LTF
Ancestral Reconstruction and Biochemical Resurrection of Hydrogenases
ERNST Leonard (GERMANY)
. - Monash Biomedicine Discovery Institute - Melbourne - AUSTRALIA
GREENING Chris (Host supervisor)
GRINTER Rhys (Host supervisor)
How did hydrogenase enzymes emerge, driving the first metabolic electron flow in early life? How did evolution bridge the transition from slow and unspecific geochemistry to the fast and specific biochemistry we know today? How were redox-active minerals first integrated into a surrounding protein shell? And what is the evolutionary rationale of the diverse hydrogenase groups and subgroups we know today, spanning more than 100,000 organisms? These and more questions will be explored in my research, focusing on the phylogenetic reconstruction, in vivo resurrection and biochemical characterization of ancestral hydrogenases. Overall, I will therefore (i) create a hydrogenase family-tree, (ii) infer the likely protein sequences of ancient hydrogenase enzymes, representing the predecessors of all extant hydrogenases, from the tree, (iii) produce them in applicable model organisms, and (iv) investigate their properties. Hydrogenases are the key drivers of hydrogen-based metabolism, catalyzing either the uptake of hydrogen, resulting in protons and electrons, or the reverse reaction, the production of hydrogen from protons and electrons. Furthermore, hydrogenases are metalloproteins, consisting of an apoprotein that is only built from amino acids, which then incorporates metal clusters that are crucial for enzymatic function, e.g. by allowing for an electron flow through the enzyme. Therefore, hydrogenases can be classified both by (i) their reaction directionality, driving either hydrogen uptake or production, and (ii) their metal cluster structure, resulting in [NiFe]-, or [FeFe]-hydrogenases. It is proposed that hydrogen served as the first electron donor during the origin of life. In evolution, hydrogenase gain-of-function therefore represents a critical step due to the rise of the first metabolic electron transport chain from hydrogen to CO2, resembling the electron flow between deep sea vents and their environment. Supposedly having originated in the transition from geochemistry to biochemistry, hydrogenases did not only exist in the Last Universal Common Ancestor, but further evolved in all three kingdoms of life. To date, hydrogenase genes have been discovered in >100,000 organisms. In addition, the occurrence of oxygen-tolerant hydrogenases illustrates that, even in geologically modern eras, hydrogenase activity is not limited to anaerobic environmental niches, but plays an important role in many aerobic microorganisms. Apart from interest regarding hydrogenase functioning, evolution and ecological relevance, these enzymes therefore gain industrial attention for their ability to consume and produce hydrogen under biotechnologically feasible conditions. However, many questions regarding this enzyme remain: the catalytic bias of hydrogenases, facilitating either hydrogen uptake or production, still lacks a mechanistic explanation. As hydrogenase enzymes are evolutionarily isolated from other enzyme classes and as these enzymes facilitated the first electron uptake in evolution, their gain-of-function remains to be unsolved. Since the abundance of hydrogenase sequences exponentially increased in recent years, the previously generated phylogenetic trees are outdated. More importantly, no efforts were so far undertaken to resurrect, produce and characterize such similarly novel and ancient enzymes. Addressing these points will be subject of my future research activities: (i) Analysis of hydrogenase diversity, (ii) thereby identifying the protein sequences of primordial hydrogenase ancestors and (iii) production of these ancestors in a model organism and (iv) characterization of the resurrected hydrogenases. Based on these findings, I can (v) propose an evolutionary rationale how hydrogenase classes emerged, (vi) model the transition from geo- to biochemistry, (vii) identify key requirements for hydrogenase activity that (ix) can pave the way for potential industrial applications.
2025
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Grant Awardees - Program Grants
A molecular roadmap for the emergence of air breathing
VARGA Máté (HUNGARY)
- Eotvos Lorand University - Budapest - HUNGARY
FABIAN Peter (Slovak Republic)
- Masaryk University - Brno - CZECH REPUBLIC
ONAI Takayuki (JAPAN)
- University of Fukui - Fukui - JAPAN
Oxygen demand is a key force driving evolution in animals, and limited availability in certain environments can prompt the development of more efficient uptake strategies. While we understand the basics of such adaptations, detailed molecular insights into environment-induced adaptive changes in the genome remain limited. Our research focuses on the paradise fish as an unconventional model organism to bridge these knowledge gaps. Paradise fish undergo a fascinating transition from gill respiration to air-breathing during their life cycle, developing a specialized labyrinth organ for atmospheric oxygen uptake. This shift provides a unique opportunity to study the molecular mechanisms governing the evolution of new organs and breathing strategies in vertebrates. Furthermore, as the development of the labyrinth organ is partially dependent on atmospheric air-breathing and without surface access the development of the organ will be stymied, this system can also inform us about the interactions between genes and environmental factors during development. Our interdisciplinary team aims to create a comprehensive three-dimensional cellular atlas of the adult paradise fish labyrinth organ, alongside a genomic-level description of its development. We will also examine the environmentally triggered labyrinth organ differentiation in fish previously not allowed to access the surface. Finally, we will test if specific genes and regulatory sequences are necessary for this developmental event by manipulating them directly in fish. Our holistic approach will enable us to explain how vertebrates adapt to new environments and how evolutionary innovations arise. Our research may also shed light on the molecular events that result in transitions in breathing strategies across vertebrate lineages, also revealing how the interplay between genes and environmental influence the traits of an organism. Finally, this work will expand our knowledge about the evolutionary potential of pharyngeal arches, the special embryonic structures that give rise to essential vertebrate features like jaws and teeth.
2025
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Long-Term Fellowships - LTF
Studying the structure and function of cortical lamination in the developing brain with MRI
FILO Shir (Israel/Germany)
. - Max Planck Institute for Human Cognitive and Brain Sciences (Max-Planck-Institut für Kognitions- und Neurowissenschaften) - Leipzig - GERMANY
KIRILINA Evgeniya (Host supervisor)
GRILL-SPECTOR Kalanit (Host supervisor)
As a parent, there’s nothing quite like the joy of watching your baby master a new skill. During the first year of life, a baby’s brain undergoes extraordinary changes to support the rapid learning of new abilities. One of the most fascinating questions in neuroscience is how the brain's structure and molecular composition develop to support its complex functions, from the formation of memories and thoughts to motor control and visual perception. Some of the most profound structural developmental changes occur in the cortex, the outer layer responsible for many cognitive functions. The cortex is organized into six distinct layers, each playing a specific role in processing information. As infants grow, these layers mature in a highly coordinated manner, with myelin and iron playing crucial roles in this development. Myelin, which insulates nerve fibers, ensures efficient communication between different brain regions. Iron supports the production of energy required for brain function and contributes to myelin production. My project focuses on investigating how myelin and iron accumulate and distribute in the cortical layers of the infant brain during the critical period of the first years of life. For hundreds of years, research on myelin and iron in the brain was limited to post mortem studies with histological techniques such as microscopy. Therefore, studying molecular changes in the living brain during development was not possible. In this project, I intend to design state of the art magnetic resonance imaging (MRI) techniques for studying myelin and iron dynamics non invasively in the brain of living infants. Traditional weighted MRI, generates images in arbitrary grayscale values, which can vary depending on scanning parameters and equipment. Quantitative MRI (qMRI) techniques have revolutionized the field of MRI by providing biophysical parametric measurements of brain tissue that can be measured in standardized physical units and compared across subjects, sites, and time points. Unlike the 'picture-like' images produced with weighted MRI, qMRI generates parametric brain maps that specifically quantify physical tissue properties. While qMRI is unlikely to ever fully resolve cellular makeup in living humans, it is extremely sensitive to the interaction of water molecules with their molecular environment. Therefore, qMRI has the potential to detect the statistics of the microstructure of brain tissue. I will develop novel biophysical qMRI models for encoding information about the iron and myelin composition in the cortex of infants. Based on these new qMRI techniques, I will map the distribution of myelin and iron across different cortical layers and monitor their changes over the first years of life. This will help in understanding whether changes in these substances are specific to certain layers or regions and how these changes influence overall brain development. Additionally, the research will investigate the relationship between structural changes and functional brain networks, assessing how alterations in myelin and iron impact cognitive development and network formation. The expected outcomes of this research include a deeper understanding of how myelin and iron contribute to functional brain development during infancy. These insights will address critical gaps in our knowledge of how structural changes in the brain support functional development.
2025
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Long-Term Fellowships - LTF
Epigenetic homeostasis as oncogenic barrier during cell differentiation
FRACASSI Cristina (ITALY)
. - Institute of Human Genetics (Institut de Génétique Humaine, IGH - CNRS) - Montpellier - FRANCE
CAVALLI Giacomo (Host supervisor)
Epigenetics refers to the biological processes that alter gene activity in a heritable manner without altering the DNA sequence. These mechanisms are key modulators of cell differentiation, during which a single cell divides, grows, and transforms into various specialized cells, such as neurons. Together, these processes guide the body’s development, shaping all the organs and tissues necessary for a living organism to function properly. Proper cell differentiation is essential for the development and health of any organism, but when this process goes awry, it can lead to pathologies like cancer. Cancer is often viewed as a genetic disease, characterized by mutations that compromise gene integrity and function. However, while adult cancers typically exhibit numerous mutations, pediatric cancers show few or no mutations but the extensive deregulation of epigenetic process. Of note, pediatric cancers seem to result from an aberrant differentiation process. This suggests that disruption of epigenetics processes could lead to an aberrant progression of cell differentiation. Yet, whether this is sufficient to induce cancer still remains elusive. This project aims to fill this gap in knowledge by disrupting these processes during cell differentiation in order to test whether cells transform into a tumoral fate and by providing a comprehensive characterization of the epigenetic profiles during and after these epigenetic perturbations. I will employ advanced techniques that manipulate the expression of epigenetic components in laboratory models of cell differentiation. I will deplete or overexpress proteins of the Polycomb group, epigenetic components whose deregulation was shown to be associated to progression of many types of cancer. I will test whether these manipulations are sufficient to transform cells into tumoral fates. In order to understand the molecular effects of the different perturbations, I will apply cutting-edge tools such as genome sequencing, epigenome profiling, 3D genome conformation mapping and super resolution imaging analysis. These techniques will provide a detailed view of the epigenetic changes occurring in individual cells and across various biological processes. Importantly, epigenetic mechanisms allow cells to acquire a \"memory\" of their previous states but, since epigenetic processes are inherently reversible, restoring epigenetic balance offers the potential to reverse their effects. In this context, I will apply transient perturbations of Polycomb protein levels in order to elucidate to what extent the alterations that they induce are reversible. In this last case, I will co-express a known activated oncogene in addition to applying a transient epigenetic perturbation, in order to test whether and how this additional insult aggravates cell transformation. By understanding the effect of Polycomb perturbations during cell differentiation and whether they are reversible upon restoration of the initial level of these components, we could gain insights into how cells maintain their identity and whether cancer might be reversed by manipulating epigenetics. In summary, this project aims to define cancer as a disease rooted in developmental cell differentiation processes and to deepen our understanding of cell differentiation and development.
2025
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Grant Awardees - Program Grants
Rediscovering Vienna’s Lost “Epigenetic” Treasure
RECHAVI Oded (ISRAEL)
- Tel Aviv University - Tel Aviv - ISRAEL
GAPP Katharina (AUSTRIA)
- Swiss Federal Institute of Technology in Zurich (ETH Zurich/ETH Zürich) - Zurich - SWITZERLAND
SASAKURA Yasunori (JAPAN)
- University of Tsukuba - Shimoda, Shizuoka - JAPAN
Our project combines history and biology in a first of its kind interdisciplinary study revisiting the research done over 100 years ago in the Biologische Versuchsanstalt (BVA). The BVA, founded in 1902, stood out with a focus on researching live animals, a new concept in those days, and its founders, led by Hans Leo Przibram, supported long-term experiments in hundreds of species of animals, many of which were never used in research later or even successfully raised in captivity. Research into acquired traits inheritance was central to the work of the most controversial scientist in the BVA - Paul Kammerer - who won global fame, only later to be called out as a fraud and take his own life. Even if Kammerer’s findings are indeed unreliable, many other well respected BVA scientists published hundreds of scientific papers in the decades the institute was active, and inheritance of acquired traits was an important part of the scientific agenda of Przibram, a renowned researcher who also had demonstrated the possibility of this type of inheritance in his own (never disproved) studies. Yet the scandal, the breathtaking success of modern DNA-based genetics, and the tragic end of the institute and its founders and members - most of whom were of Jewish descent who were murdered by the Nazis - meant that the unique science done in the BVA was never continued. In the past 15 years, the possibility of transgenerational epigenetic inheritance has gained a new life owing largely to research conducted using C. elegans nematodes. Prof. Oded Rechavi, who is leading the project, was a pioneer in describing an RNA based molecular mechanism enabling such inheritance in the tiny worm. Now, the challenge is to demonstrate the existence of similar mechanisms in other organisms. The research done in the BVA could be discovered as a scientific treasure trove for accomplishing such a goal. Therefore, we propose to (1) Translate and study the BVA papers to select the works that are worth re-visiting. (2) Replicate of the rediscovered studies. (3) Use molecular research to discover new inheritance mechanisms in the BVA models. To do this we assembled a unique team of historians and biologists specializing in the different animals we plan to focus our replication efforts on, and in the study and discovery of the molecular mechanisms involved in epigenetic inheritance research.
2025
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Long-Term Fellowships - LTF
Molecular mechanisms underlying the evolution of central neural circuits and behavior
GIEZ Christoph (GERMANY)
. - The Francis Crick Institute Ltd - London - United Kingdom
PRIETO GODINO Laura Lucia (Host supervisor)
The brain is one of the most complex structures in the universe and controls all our behaviors. This means that the immense variety of behaviors displayed by different animals – including ourselves – arose through the evolution of the complex neuronal networks within brains. However, we still do not know how central neuronal circuits change over time, integrating modifications within the brain's highly interconnected networks. Particularly puzzling is that evolution acts on genes but behavior arises through the activity of neuronal networks. How are these two levels integrated? How do evolutionary changes on the gene-level lead to changes in neuronal circuits that themselves lead to behavioral divergences across animals? Understanding the connection between genes, neuronal network function, and behavior will have far-reaching implications beyond the field of circuit evolution, as it will help us to better understand how brains work, and how they can be modified to precisely alter their function. To explore this question, we need a simple yet effective model. The larval olfactory system of the fruit fly, Drosophila, offers a powerful solution because: 1) different Drosophila species have evolved diverse odor-guided behaviors, 2) the olfactory system is numerically simple yet parallels more complex circuits, and 3) the availability of molecular tools and resources. I will use this system to pinpoint key areas of central neuronal circuit evolution, both in terms of function and genetics, by comparing two Drosophila species. One of the uniquely powerful methods I will use is comparative connectomics. Connectomics is a method by which we can create a map of all of the neuronal connections within a circuit in the brain. I will use the connectomic maps generated for two different species, and compare them to each other to identify what has changed in the brain of these two species. Then, I will make use of the powerful genetics available in Drosophilids to investigate how these connectivity changes alter the function of the brain circuits. In particular, using genetics, I will introduce tools that enable us to visualize and manipulate the neuronal activity of networks within the brain in the two species. This will help us to understand whether the observed changes in neuronal connections have a functional consequence. Thereby, I will be able to understand how evolution tinkers with neuronal circuits and changes lead to the differences in behavior between the two species. Because the networks in the brain are so complex, I will use mathematical modelling to help understand their function. Mathematical modelling will be extremely powerful because it allows to simplify complex interactions, and makes predictions for mechanisms, which can be tested in experiments. Next, since evolution acts on genes, I will investigate how the activation of specific genes in the neurons of one species but not the other lead to the observed connectivity differences. I will leverage these insights to re-engineer neuronal circuits across species, using the powerful genetic tools available in D. melanogaster. To re-engineer the behavior of D. melanogaster, I will take the genes from D. erecta and transfer them into D. melanogaster which will eventually lead to a change in neuronal circuitry and behavior. One prediction is that neurons responsible for processing and filtering inputs are hotspots of change and are responsible for the emergence of new behaviors. One indicator is that these neurons are likely to exhibit variations within a species, a crucial element for evolutionary changes to happen. Uncovering the genetic basis of these changes will enhance our understanding of the intricate interactions between genes, neuronal circuits, and behavior in the context of evolution. This will uncover fundamental principles of sensory processing in the brain and shed light on the most exciting question: how do brains evolve?
2025
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Long-Term Fellowships - LTF
The regulation of mitochondrial dynamics by local protein translation in neurons
GROZA Raluca (ROMANIA)
. - Swiss Federal Institute of Technology in Zurich (ETH Zurich/ETH Zürich) - Zurich - SWITZERLAND
KLEELE Tatjana (Host supervisor)
Mitochondria perform numerous cellular functions and form a highly dynamic network which rapidly modulates its structure through fission and fusion to meet cellular needs. Disturbances in mitochondrial dynamics have severe bioenergetic consequences in all cells but primarily manifest in neurological disorders. In neurons, mitochondria face particular challenges: thousands of mitochondria have to be distributed throughout the neuronal arbores to account for the high energetic demand of neurons. At the same time, neurons are not renewed over a humans' lifetime, meaning that oxidative damage and mitochondrial DNA mutations escaping quality control accumulate over decades. However, little is known about how mitochondrial dynamics ensure lifelong adaptation and rejuvenation of the mitochondrial network. Given that local protein synthesis is an important process that enables the polarized functions of neurons, we hypothesize that it also plays a role in mediating mitochondrial dynamics. However, barriers in spatial and temporal imaging resolution have made it difficult so far to study local protein synthesis in neurons. In this project we will investigate if local protein synthesis is responsible for the local regulation of fission, fusion and mitophagy and how it supports the maintenance of mitochondrial homeostasis in human neurons derived from induced pluripotent stem cells. We will develop a novel live-cell super-resolution imaging pipeline to characterize the dynamics of local mRNA translation in different neuronal compartments based on the SunTag reporter system. Concomitantly, we will image the mitochondrial dynamics events that are mediated by local protein translation in real-time in live neurons. Lastly, we aim to compare local protein translation and mitochondrial dynamics between healthy and aged neurons to identify possible mitochondrial dysfunctions that lead to aging or neurodegenerative diseases. Our proposed methodology will not only allow us to address so far unresolved questions in the mitochondrial field, but it can later also be expanded towards other fundamental cellular processes, potentially opening new research directions.
2025
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Long-Term Fellowships - LTF
Local genetic clocks for linking memories across time
GÜR Burak (TURKEY)
. - Friedrich Miescher Institute (Friedrich Miescher Institute for Biomedical Research, FMI) - Basel - SWITZERLAND
FELSENBERG Johannes (Host supervisor)
Imagine trying to recall events from your day: your brain naturally links moments that happen close together, like having lunch and then meeting a friend. But if more time passes between events, like your morning coffee and a meeting two days later, your brain keeps those memories separate. This ability to link or separate memories based on time is crucial for making sense of the world, but how does the brain decide which memories to link? What mechanisms track the time between events and determine how we remember them? My research aims to answer these questions by exploring the role of local molecular clocks, such as clock genes, in the brain. Clock genes are well-known for controlling circadian rhythms, the 24-hour cycle that governs sleep and wakefulness. However, preliminary findings suggest that these genes may also play a critical role in tracking time between experiences, helping the brain decide whether to link or separate memories. Clock genes may serve as internal timers, not just for day and night but for timing the gaps between important moments in our lives. I use Drosophila melanogaster, or fruit flies, as a model for studying how clock genes influence memory. Fruit flies offer a powerful system for brain research because of their genetic tools and the detailed maps we have of their brain’s memory centers. Though flies may seem far from humans, the basic principles of memory formation and time tracking are shared across many species, meaning that what we learn from flies could apply to humans too. We know that experiences occurring within a few hours of each other are more likely to be linked into a single memory, while events spaced further apart are stored separately. For example, in flies, a memory of a rewarding experience (like smelling a sweet odor in a room) can be erased or modified if the fly encounters conflicting information (like the absence of the sweet odor) within a specific time window. I think that clock genes, which are active in the brain's memory centers, may control this time window for linking memories. To test this, I’ll manipulate the activity of clock genes in neurons that form memory and observe how it affects memory linkage. By using advanced imaging techniques, I’ll watch neurons in real-time as the flies experience events spaced closely or far apart. This will help uncover how clock gene activity impacts memory circuits and their ability to link memories. Ultimately, this research will reveal how our brains use internal clocks to organize experiences. Understanding these processes could have important implications for treating memory-related disorders such as PTSD or addiction, where memories are either linked too strongly or not enough. By revealing the responsible genes, this work could lead to new approaches for treating these conditions.
2025
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Grant Awardees - Program Grants
Dancing genomes – mapping chromatin’s material properties with retinal development & disease
ROBSON Michael (United Kingdom)
- Max Delbrück Center for Molecular Medicine - Berlin - GERMANY
TENREIRO Sandra (PORTUGAL)
- Universidade Nova de Lisboa - NOVA Medical School - Lisbon - PORTUGAL
MICHIELETTO Davide (ITALY)
- University of Edinburgh - Edinburgh - United Kingdom
HANSEN Anders (United States)
- Massachusetts Institute of Technology - MIT - Cambridge - United States
Chromatin, the structure that organizes our DNA, is a biological machine made of soft, flexible parts. For this machine to function, it must shift, bend, and rearrange to perform essential tasks, from repairing DNA to activating or silencing genes. However, how chromatin’s physical properties—whether it behaves like a liquid, solid, or gel—affect its ability to perform these functions remains largely unknown. This is because observing chromatin’s movements in living cells, and across the various size scales it operates on, has been extremely difficult. Traditional models offer limited insight, as chromatin moves too little to capture meaningful data across the range of scales needed to fully understand its behavior. Our project aims to solve this by studying the unique, extreme dynamics of chromatin in the retina, the part of the eye responsible for vision. In most cells, inactive chromatin stays at the edges of the nucleus, while active chromatin occupies the center. However, in the rod cells of nocturnal mammals like mice, this arrangement is reversed after birth to help the eyes capture more light. This rare “inversion” of chromatin offers a unique opportunity to observe dramatic chromatin movements and uncover its physical properties during global reorganization. Our approach combines genetic tools, high-resolution imaging, and computational modeling to capture chromatin behaviors across multiple scales. By controlling chromatin inversion in mouse retinal cells, we will observe chromatin’s movements in real time. We will measure movements at the level of individual genes and larger chromatin regions, providing a comprehensive picture of chromatin dynamics. Simulations will test different models and parameters to understand whether chromatin acts more like a liquid, solid, or gel and why. We will extend our work to human retinal organoids—lab-grown models of the human retina—to investigate whether inappropriate chromatin inversion occurs in eye diseases like macular degeneration and how this might contribute to vision loss. This project unites experts in genetics, imaging, computational biology & neurodegeneration to study chromatin in ways not previously possible. By treating chromatin as a dynamic machine that must move and reorganize, we aim to uncover new insights into how our genomes work and how chromatin malfunctions promote disease.
2025
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Long-Term Fellowships - LTF
Neuromodulation of representational stability during learning under uncertainty
HATASHITA Yoshiki (JAPAN)
. - University Hospital Bonn (Universitätsklinikum Bonn) - Bonn - GERMANY
ROSE Tobias (Host supervisor)
Recent advances in chronic and large-scale neuronal recording in behaving mice have shown that neuronal responses against the same inputs can gradually change over time in various brain regions (Ziv et al., 2013; Driscoll et al., 2017) – even in the primary sensory area of olfaction (Schoonover et al., 2021) and the visual cortex (Rose et al., 2016; Marks and Goard, 2021; Deitch et al., 2021; Bauer et al., 2023). Such “representational drift” poses the critical question of how the brain achieves reliable memory, perception, and action with unstable neuronal processing. Computational studies suggest that representational drift may serve to avoid local minima, reduce overfitting, provide flexibility for continuous learning, or connect temporally separated memories. However, little is known experimentally about the cause and function of representational drift. Specifically, systematic clarification of (i) the behavioral state-dependence of representational drift, (ii) its modulation by task variables, and (iii) its relation to the cell-autonomous molecular makeup of neurons is needed. Here, I propose to address these questions using a visually guided foraging task with certain and uncertain reward outcome probabilities and explore how continuous learning under uncertain conditions affects the stability of neuronal representation in the visual cortex. In this task, mice need to adapt to uncertain circumstances by continuously updating the behavioral outcome history and internal model based on the experience of reward probability. As the cholinergic signaling encodes behavioral outcome uncertainty and re-balance feed-forward and top-down integration (Yu and Dayan, 2005), I hypothesize that higher outcome uncertainty accelerates overall representational drift while shaping neural activity differently in neuronal subtypes under neuromodulatory control. To test this, I will establish the behavioral task built on a head-fixed virtual reality system and perform a combination of chronic two-photon calcium imaging and correlated three-dimensional spatial transcriptomics. Moreover, I propose to monitor and control cholinergic axonal activity during the task to dissect the involved neuromodulatory circuits. The goal is to identify key genetic profiles associated with individual or population neuronal stability and state-dependent modulation. This could be a specific neuronal subtype or sub-network defined by molecular markers such as neuropeptides, adhesion molecules, or heterogeneous combinations of neuromodulator receptors and distinct downstream signaling pathways of immediate early genes. Collectively, this study will advance the experimental characterization of representational drift by shedding light on its behavioral state dependence, neuromodulatory circuits, and molecular specificity, likely providing new genetic access and theoretical frameworks to address the biological significance of representational drift in future studies.
2025
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Grant Awardees - Program Grants
Universal Biochemistry of RNA in the Cold
RITORT Felix (SPAIN)
- University of Barcelona - Barcelona - SPAIN
WOODSON Sarah A. (United States)
- Johns Hopkins University - Krieger School of Arts & Sciences - Baltimore - United States
HOLLIGER Philipp (SWITZERLAND)
- MRC Laboratory of Molecular Biology - Cambridge - United Kingdom
Life exists even in the coldest environments on earth, yet we know little about how RNA molecules needed for all living things continue to function at subzero temperatures. Using a specialized microscope capable of studying single molecules of RNA at temperatures down to the freezing point of salt water, we recently discovered that RNA molecules acquire new and unexpected properties at subzero temperatures. At low temperatures, sequence-independent 2’-hydroxyl- water interactions become more important than sequence-dependent base pairing. These changes are predicted to profoundly alter the ability of RNA molecules to fold into 3D shapes and catalyze biochemical reactions. We hypothesize that RNA catalysts may have first evolved at subzero temperatures, potentially within semi-frozen environments such as interstitial brines. Our findings predict a much richer ensemble of RNA structures and more error-prone RNA replication in the cold. This would have accelerated primordial RNA evolution and could profoundly impact the function of present-day RNAs in the cold, with applications to biotechnology, pharmaceuticals, and food science.
2025
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Cross Disciplinary Fellowships - CDF
Mesoscale and Microscale Organization in C. elegans embryo
HONG Yuri (South Korea)
. - Max Planck Institute of Molecular Cell Biology and Genetics (Max-Planck-Institut für Molekulare Zellbiologie und Genetik) - Dresden - GERMANY
HYMAN Tony (Host supervisor)
Our cells are not just a jumble of molecules—they are highly organized environments where precise positioning and interactions are essential for proper function. Understanding how cells achieve this internal organization is one of the great challenges of biology. Our research focuses on a key aspect of this process known as \"polarity,\" which refers to the way cells establish distinct regions with different molecular compositions. This is crucial for many cellular activities, such as division, movement, and development. We are studying these processes in a tiny roundworm called Caenorhabditis elegans. Despite its simplicity, this organism shares many biological mechanisms with humans, making it an ideal model for understanding fundamental aspects of cell biology. During early development, C. elegans embryos create a \"polarity\" that determines the future organization of cells. A protein called MEX-5 plays a central role in this process by forming two different regions within the cell: a high concentration in the anterior (front) and a low concentration in the posterior (back). This gradient is crucial for setting up the embryo’s body plan and ultimately for the formation of specialized cells, including those that will become the germ cells, which give rise to eggs and sperm. MEX-5 does not work alone; it interacts with RNA molecules to form clusters of various sizes that move through the cell differently depending on where they are. Our project aims to explore how these MEX-5 clusters form, what controls their size and movement, and how these properties contribute to the establishment of polarity in the developing embryo. Using advanced imaging techniques, we will observe MEX-5 in live C. elegans embryos, tracking its distribution and behavior in real time. We will also create and analyze mutant versions of MEX-5 that have altered abilities to bind RNA, helping us understand how these interactions regulate the protein’s behavior in living cells. Additionally, we will recreate MEX-5 clusters in a test tube to study their physical properties and interactions with RNA in a controlled setting. By combining these in vivo (in living organisms) and in vitro (in the lab) approaches, we aim to uncover the detailed mechanics of how these clusters form and function. Our research could have far-reaching implications. Understanding the principles of cellular organization at the molecular level could inform new strategies for treating diseases where cellular organization goes awry. Additionally, the techniques we develop for studying protein-RNA clusters could be applied to other biological systems, advancing our understanding of cell biology more broadly. This project is an exciting step forward in the quest to understand how cells build their internal landscapes and maintain order amidst the chaos of thousands of interacting molecules. Through this work, we hope to contribute to a deeper understanding of the fundamental principles that make life possible.
2025
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Long-Term Fellowships - LTF
Mechanisms of translation reprogramming during embryonic diapause
JENTOFT Ida (NORWAY)
. - Research Institute of Molecular Pathology (Forschungsinstitut f molekulare Pathologie GesmbH, IMP) - Vienna - AUSTRIA
PAULI Andrea (Host supervisor)
Animal life has evolved various strategies to survive and reproduce during periods of unfavourable conditions. One example is embryonic diapause. Diapause is a reversible, dormant state in which development in a healthy embryo is paused awaiting reestablishment of a favourable environment. Although it has been described in a wide range of species, our mechanistic understanding of diapause remains poor. For example, diapause is associated with a stark reduction in protein synthesis, but it is not known how the protein synthesis machinery, the ribosomes, are temporarily rewired to support a prolonged dormant state. Nor is it understood whether different cell types or tissues within the same organism adapt differently to diapause. The main goal of this research project is to understand how regulation of protein synthesis and organization of proteins within the cell are rewired during diapause. To this end, I will study the model organism Nothobranchius furzeri also known as the African Turquoise Killifish. Embryos of this fish species enter diapause in response to the periodic drying out of their habitats. Remarkably, in their dormant, developmentally arrested state, the embryos survive the dry season and are ready to continue development once water returns to the pond. To study diapaused-induced changes to protein synthesis, I will assess alterations to the ribosome itself, the factors that act on the ribosome, and the messenger RNA (mRNA) from which proteins are synthesized. I will also investigate changes in how proteins interact with each other during diapause. If proteins change conformation and interaction partners during diapause, this may change their activity and localization, ultimately influencing the state of the cell. A diapaused killifish embryo is composed of around 30,000 cells. These cells have different cell type identities and make up different tissues within the embryo. Because most studies to date have investigated global changes during dormancy, treating the whole embryo as a single entity, we know very little about whether different cells in different tissues respond differently to diapause. With such a heterogeneous composition of cells, it is, however, likely that different tissues adopt slightly different responses when diapause is induced. To test this hypothesis, I will analyze the proteins and mRNAs within single tissues and even single cells. If the hypothesis is correct, I would observe that the changes that occur between active development and diapause differ between cell types. Understanding whether and how various tissues adopt a dormant state could have impacts beyond the field of diapause and cellular dormancy. For example, cancer cells can enter a dormant state in which they are unresponsive to therapeutics. These dormant cells can later be activated and repopulate the tissue causing the tumor to reoccur. If the dormant state of the cell is related to the tissue in which it resides, then knowing the potential factors at play could be crucial in identifying new drug targets. Taken together, the outcomes of this project hold promise for the discovery of novel and potentially universal regulators of diapause. Through this research, we aim to advance our understanding of the fundamental principles governing both cellular and organismal dormancy.
2025
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Grant Awardees - Early Career
MetaCrystal: Metabolic principles of intracellular crystallization
JIMENEZ-ROJO Noemi (SPAIN)
- University of the Basque Country (Euskal Herriko Unibertsitatea, EHU; Universidad del País Vasco, UPV; UPV/EHU) - Leioa - SPAIN
MATEUS Rita (PORTUGAL)
- Max Planck Institute of Molecular Cell Biology and Genetics (Max-Planck-Institut für Molekulare Zellbiologie und Genetik) - Dresden - GERMANY
MONJE Viviana (United States)
- The Research Foundation for The SUNY on behalf of University at Buffalo - Buffalo - US
Many living organisms are capable of producing organic crystals inside their cells to fulfill a variety of functions. For example, the compound eyes of certain crustaceans use crystals to amplify their light sensitivity in dim-light habitats. Another well-known example is the chameleon, which takes advantage of the light-reflecting properties of crystals to swiftly alter its skin color. Therefore, failure to regulate crystal formation properly can be detrimental to tissue and organ function, severely affecting the ability of the organism to survive and reproduce. The zebrafish, a vertebrate model organism, also produces crystals that play a key role in pigmentation. These are formed within specialized cells called iridophores, inside dedicated subcellular compartments, or organelles, known as iridosomes. Here, control of crystal size, shape, and assembly take place with a precision that currently far exceeds our abilities to grow such structures synthetically. In the proposed study, we plan to uncover how this process occurs, considering an essential, but so far unexplored, structure: the lipid membrane that encloses each crystal inside the cells. We want to understand which molecules are found at the iridosome membrane, their biochemical nature, and to what extent those can contribute to such exquisite crystal formation. For this purpose, we will apply a highly interdisciplinary approach combining cutting-edge techniques from molecular biology, such as CRISPR-Cas9, with biochemistry, like mass spectrometry, and molecular modeling We will make use of novel chemical biology methods to measure and manipulate iridosomal membrane biophysical properties and track protein function in vivo in zebrafish, and in iridophore cell cultures. The data obtained will inform us on how to generate and reconstitute synthetically a biomimetic system able to produce crystals at scale and morphology to those of zebrafish, using a combination of biological and chemical transformations under physiological conditions. We expect that the results we obtain will facilitate the development of therapeutics to treat diseases where aberrant crystallization occurs, such as kidney stones and gout. In addition, they will contribute to new protocols to synthesize organic crystals for a variety of applications in the areas of optics and material science.
2025
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Long-Term Fellowships - LTF
Towards programmable multicellular logic networks
JONKERGOUW Christopher (NETHERLANDS)
. - Massachusetts Institute of Technology - MIT - Cambridge - United States
VOIGT Christopher (Host supervisor)
Cooperation among cells is a key evolutionary innovation, allowing specialization and distinct roles within a community. For example, bacterial biofilms show how cooperation enhances survival through shared metabolites and resistance to environmental stresses. Specialization enables spatial segregation of functions, such as one species focusing on adhesion while another produces energy-intensive compounds. These systems have long intrigued microbiologists. In contrast, synthetic biology often prioritizes the creation of new, non-natural functions and constraints within living cells. Drawing inspiration from fields like engineering and photonics where increasing the number of logic circuits on chips results in greater computational power, synthetic biology aims to impose more rules and programmable controls on biological systems. However, as the complexity and quantity of these synthetic functions grow, they impose a significant burden on the cells, diverting critical resources away from essential processes required for survival. With the increase in complexity, the challenges in engineering such systems escalate dramatically. This project aims to overcome these challenges by drawing inspiration from natural microbial communities and engineering cooperative behavior among microbes. Instead of burdening a single cell with all the synthetic functions, the overall logic circuit is divided into smaller, manageable pieces and distributed across different cells. These cells then communicate and work together to execute the full function of the circuit. By engineering cooperation among cells, the workload is distributed, reducing the burden on individual cells and allowing them to specialize in specific tasks, much like the division of labor seen in natural systems. This strategy has the potential to significantly enhance the complexity of engineered biological systems, opening up new possibilities for industrial and medical applications. - One such example we explore within this project, where we demonstrate the potential of engineered multicellular systems in medical applications, particularly in cancer diagnostics and/or treatment. Cells can be programmed to detect specific biomarkers or disease states, triggering coordinated therapeutic responses. Multiple cell types work together to detect a wide array of cancer-specific miRNAs. Once the biomarkers are identified, one set of cells can produce a targeted therapeutic protein, while another type enhances the body's immune response. - In industrial settings, engineered multicellular systems could enhance the production of biofuels, bioplastics, and other valuable compounds. By dividing complex metabolic pathways across different microbial strains or species, each strain can specialize in producing key intermediates, improving overall efficiency and yield. While one set of engineered cells is optimized for the production of specific chemical precursors, another set converts these intermediates into final products like biofuels or biodegradable plastics. - In agriculture biotechnology, engineered microbial consortia could be utilized to simultaneously improve soil health, enhance nutrient availability, and protect plants from pests or pathogens. For example, different engineered bacteria could colonize plant roots and perform complementary functions—one type fixing nitrogen, another secreting growth-promoting substances, and yet another producing antimicrobial compounds that protect the plant from infections. These cooperative systems would promote sustainable agriculture by reducing the need for chemical fertilizers and pesticides while improving crop yields. To summarize, this project explores a revolutionary new strategy towards increasing the capacity and complexity of genetic circuit design, with the potential to generate numerous applications accross multiple biological disciplines.
2025
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Grant Awardees - Program Grants
Microbial and chemical mechanisms of rapid fear signaling
ROBERTS S. Craig (United Kingdom)
- University of Stirling - Stirling - United Kingdom
KALAN Lindsay (CANADA)
- McMaster University, Faculty of Health Sciences - Hamilton - CANADA
WILLIAMS Jonathan (GERMANY)
- Max Planck Institute for Chemistry - Mainz - GERMANY
Many species, including humans, use odors to communicate. These odors are typically complex, and describing them is challenging. Furthermore, we do not know much about how they are produced. However, in some species, such as hyenas and some primates, individuals may share similar skin bacteria that produce distinctive chemical compounds as part of their metabolism; these compounds have become co-opted for communication and are how the animals infer species, sex, and social group membership. We aim to understand the mechanisms by which human odors are produced. We focus on emotional odors, especially fear, for two main reasons. First, we know that humans do produce a distinct 'fear odor,' even though we do not know the precise chemical compounds involved nor whether the skin bacteria are responsible for them. Second, a signal of fear requires a very rapid response—in a matter of seconds or minutes—a change that is much faster than any microbially mediated signal studied to date, in any species. Indeed, we do not know whether bacterially produced odors are even possible on this time scale; addressing this possibility is bold and innovative but could lead to a discovery of enormous significance. Our interdisciplinary team has expertise in the psychology of odor communication, dynamic changes in skin bacteria, and analysis of airborne (volatile) chemical compounds. We will study the odor of fear by showing people scenes that arouse emotional responses (including fear) at the same time as measuring changes in bacterial metabolic activity and the release of chemical compounds from the skin. We thus aim to provide the first description and identification of rapid changes in bacterial activity and odor chemistry as people experience fear. Next, we will attempt to confirm the odor production pathway by analyzing the chemicals produced by our candidate bacteria in the lab, as they are cultured on an artificial blend of human skin secretions. Finally, we will test how people respond to the identified chemical compounds. We will compare people's emotional responses when they are exposed to the isolated compounds with how they respond to the complete (natural) odor of scared people; if the responses are comparable, it will suggest that we have correctly identified the compounds responsible for the smell of fear.
2025
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Long-Term Fellowships - LTF
Unfolding the mechanisms of Tiamat, a unique prokaryotic defense system
KOOPAL Balwina (NETHERLANDS)
. - Institute of Science and Technology Austria - Klosterneuburg - AUSTRIA
BRAVO Jack (Host supervisor)
Like other living beings, bacteria are under constant threat of being attacked by viruses. To defend themselves against these invaders, bacteria have evolved a variety of immune systems that can recognize the infection. Upon detection, the immune system then either neutralizes the virus directly, or kills the infected host cell to prevent spread of the virus to neighbouring cells. Due to their ability to detect viruses with great specificity, several bacterial immune systems have been applied in various biotechnological applications with great success. However, new bacterial immune systems are being discovered at a rapid pace, and the mechanisms that underly many of these systems remain to be investigated. One of these systems is the recently discovered Tiamat system. Tiamat is unique among bacterial immune systems because (i) whereas other bacterial immune systems consist of multiple small proteins, Tiamat consists of only one large protein that must be responsible for both sensing the virus and executing the immune function, and (ii) this protein has a unique domain that is known from entirely different cellular processes, which has not been described as part of a bacterial defence system before. It was demonstrated that Tiamat confers moderate immunity against two viruses, but it is unknown how the infection is recognized, and how immunity is secured. We aim to resolve these knowledge gaps. To do so, we will first identify viruses that are more strongly affected by Tiamat-based immunity. We will then use these viruses to discover the trigger of activation by identifying proteins that bind to Tiamat. Subsequently, we will assess what happens after Tiamat gets activated. Our preliminary analysis of the Tiamat system has indicated that upon activation it may degrade DNA and/or RNA, presumably from the infecting virus. We will first confirm whether this is the case. Then, we will elucidate the underlying mechanism of Tiamat by using the identified trigger for Tiamat activation, as well as a suitable DNA/RNA target, to recapitulate the enzymatic activity of Tiamat outside of the bacterial cell. Subsequently, we will use the outcome of these experiments as a guide to visualize the activation of Tiamat using cryo-EM. The resulting structural models of Tiamat will provide a molecular basis for its function. Lastly, we will explore divergent Tiamat systems to increase our mechanistic understanding of Tiamat in a broader sense, and provide guidance for engineering these systems for their application in biotechnology. Together, these findings will provide critical insights into a unique, uncharacterized bacterial immune system, both on a cellular and on a molecular level. This will not only broaden our understanding of bacterial immune systems in general, but will also help us understand how a domain that is typically associated with entirely different biological processes could be adapted to function as an immune system.