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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
2024
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Long-Term Fellowships - LTF
Design and build a synthetic single cell epigenetic oscillator
ABDULLA Amith Zafal (INDIA)
Physics - Brandeis University - Waltham - United States
KONDEV Jane (Host supervisor)
RAGUNATHAN Kaushik (Host supervisor)
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2024
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Grant Awardees - Early Career
Mechanical control of hidden embryonic boundaries
ALMUEDO-CASTILLO Maria (SPAIN)
- Centro Andaluz de Biología del Desarrollo/ CSIC - Sevilla - SPAIN
MONGERA Alessandro (ITALY)
- University College London - London - United Kingdom
SERRA Mattia (ITALY)
- The Regents of the University of California, San Diego - San Diego - United States
The developmental fate of each embryonic cell has been extensively studied with both classical lineage tracing and modern omics technologies. However, how cells are primed for distinct fates before acquiring their transcriptional identity is unknown. Here, we set out to identify the earliest mechanical signatures that mark fate separation while cells navigate the embryo along complex migratory paths.
We posit that similar to complex atmospheric and oceanic large-scale flows, hidden material surfaces known as Lagrangian Coherent Structures (LCSs) represent a novel kind of embryonic boundaries organizing cellular flows and patterning. Using dynamical systems and control theory, we will develop a technique to identify LCSs of in-toto 3D zebrafish gastrulation from sparse cell tracks. Specifically, we will focus on multicellular repellers, LCSs that compartmentalize the embryo very early, setting cells apart before they acquire distinct transcriptional profiles. Repeller-mediated cellular flows are invisible to standard methods based on cell velocity and trajectories. Therefore, we propose an integrative approach to unveil the mechano-dependent epigenetic modifications instructing fate bifurcation.
First, we will determine the viscoelastic properties that cells experience across the repellers. We will quantify this highly dynamic mechanical landscape in vivo and in situ with unprecedented spatiotemporal resolution using live microscopy, image analysis, and novel rheological techniques. Second, we will analyze how divergent mechanical properties along opposite repeller-mediated cellular flows impact chromatin accessibility and marks, resulting in transmissible changes in gene regulation that will dictate cell lineage differentiation. Third, we will devise a data-driven differentiation model for cells across repellers, accounting for epigenetic and mechanical cues--effectively providing a mechanics-mediated Waddington potential.
This proposal will revolutionize the way we understand early embryo compartmentalization and elucidate its very first mechanical and epigenetic drivers.
2024
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Grant Awardees - Program Grants
Scaling the impact of viruses from single cells to the global methane cycle
ANANTHARAMAN Karthik (United States)
- University of Wisconsin-Madison (Board of Regents University of Wisconsin System) - Madison - United States
EMERSON Joanne (United States)
- The Regents of the University of California (University of California Davis) - Davis - United States
MALIK Ashish (INDIA)
- University of Edinburgh - Edinburgh - United Kingdom
NICOL Graeme (United Kingdom)
- CNRS (Centre National de la Recherche Scientifique/French National Centre for Scientific Research) - Ecully - FRANCE
Viruses kill up to 40% of ocean microbial cells daily, impacting global ocean food webs, carbon and nutrient cycling, and climate. Soil viruses likely play similarly essential roles in terrestrial ecosystems, yet their diversity and impacts are virtually unknown. Here we aim to quantify and predict the role of viruses in ecosystem methane flux in climate-significant peatlands from multiple continents. Viruses and their microbial hosts that produce and consume methane will be studied across scales from single cells to communities to ecosystems. We will test the overarching hypothesis: viruses in peatlands affect the growth, activity, interactions and death of methane cycling prokaryotes thereby changing the ecosystem methane flux. This will be achieved by characterizing the spatial structuring of virus-host interactions across different locations and within each location across the peat column with changes in water content, oxygen and hydrological connectivity, and develop novel approaches for quantifying the temporal dynamics and fluxes of carbon transfer between viruses and their hosts. Through novel experimental and computational approaches, we will investigate the strategies of virus infection, host specificity, and outcomes in terms of methane uptake or loss using microfluidics, single cell genomics, viromics, metagenomic- and protein- stable isotope probing. We will leverage deep learning-based tools to improve viral protein annotations and host predictions to advance viromics research in peatlands and beyond. At the community scale, we will quantify the contribution of viral-host interactions to ecosystem methane cycling in the lab and field by quantifying methane production and oxidation rates and identify sources and fate of methane using stable carbon isotope analysis. Finally, a population dynamics model will simulate virus-host interactions to create generalisable predictions of methane flux rates. This interdisciplinary project with complementary expertise from multiple countries will enable generation of novel understanding of virus-prokaryote interactions across temporal and spatial scales to link viruses to the global cycling of a potent greenhouse gas.
2024
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Long-Term Fellowships - LTF
Why do stressed bats shed more viruses?
ANSIL B R (INDIA)
Department of Biology - The Board of Regents of the University of Oklahoma (University of Oklahoma) - Norman - United States
BECKER Daniel (Host supervisor)
BANERJEE Arinjay (Host supervisor)
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2024
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Grant Awardees - Program Grants
Trapped in ice
BABIN Marcel (CANADA)
- Laval University (Université Laval, Québec) - Quebec - CANADA
FRIPIAT Francois (BELGIUM)
- Université libre de Bruxelles (Free University of Brussels, ULB) - Brussels - BELGIUM
MARÉCHAL Eric (FRANCE)
- Laboratoire de Physiologie Cellulaire et Végétale - Grenoble - FRANCE
PRAKASH Manu (INDIA)
- The Board of Trustees of the Leland Stanford Junior University - Stanford - United States
Sea ice is a major, at times ubiquitous, feature of the biosphere, where bacteria, archaea and eukaryota can survive and thrive at freezing and deep freezing temperatures. Although of fundamental importance to understand the origin of life and its occurrence elsewhere in the universe, the questions of how life colonizes sea ice while concentrating up to 20,000 times in this natural bioreactor, and adapts to drastic phase shifts during ice growth remain mysterious. Meshing biology, glaciology, bioengineering, biochemistry, and optics, this project will use ice-dwelling microalgae as models to characterize at both the submillimeter crystal size and textural subcentimeter scales the physical and biochemical processes that lead to colonization of growing sea ice, and the physiological and genetic controls underpinning the survival and plasticity of biota during phase changes. Purpose-built sea ice chambers will allow the growth of various types of sea ice and monitor interactions with microalgae during key phases including nucleation of ice crystals, scavenging of cells by ice crystals, and colonization of this porous medium filled with brine inclusions. To specifically address the possible role of nucleation in the colonization of sea ice by microorganisms, experiments will also be conducted using a novel microfluidic approach where individual diatom cells will be injected in pressure-controlled supercooled seawater.
2024
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Grant Awardees - Early Career
Deciphering the evolution, cellular biology and biogeochemistry of symbioses in anaerobic eukaryotes
BEINART Roxanne (United States)
- University of Rhode Island - Narragansett - United States
HUSNIK Filip (CZECH REPUBLIC)
- Okinawa Institute of Science and Technology Graduate University - Onna-son, Okinawa - JAPAN
STAIRS Courtney (CANADA)
- Lunds universitet (Lund University) - Lund - SWEDEN
Symbiosis with prokaryotes is a key adaptive strategy used by unicellular eukaryotes (protists) that live without oxygen. Instead of using oxygen as an electron sink, anaerobic protists rely on electron sharing with a prokaryotic partner. Although this process, known as syntrophy, has evolved many times independently, the metabolic adaptations and cellular integration underlying these partnerships are poorly known. This is despite the fact that protist-prokaryote syntrophies are ubiquitous in oxygen-depleted habitats, where they are key to biological food webs and the cycling of globally important compounds (e.g., the greenhouse gas methane). Here, we will combine evolutionary genomics, microbial physiology, geochemistry, and advanced cell biology methods to determine convergent metabolic strategies and symbiosis infrastructure across three distinct eukaryotic lineages (ciliates, jakobids, and breviates) separated by almost two billion years of evolution. We hypothesize that these distinct lineages will share electrons via the exchange of hydrogen using a combination of lineage-specific and conserved metabolic and structural adaptations, and such interactions will be sensitive to environmental factors. Objective 1: Using genomics, we will deliver high-quality genomes of these representative protists and their symbionts. These genomes will be used to infer metabolic interactions between different partners and, using phylogenetic inference, we will identify lineage-specific and conserved features of symbiosis. Objective 2: We will optimize growth conditions of each microbial culture and establish methods to quantify cell growth under different abiotic parameters such as temperature and oxygen concentration. Metabolic flux analysis will be used to discover which metabolites are shuttled between the protists and their symbionts. Objective 3: We will establish high-resolution single-cell imaging to map the ultrastructure of the protist:prokaryote interaction. This imaging will be coupled to spatial proteomics that will deliver a subcellular atlas of protein localization. Our results will deliver a holistic understanding of electron-sharing symbioses in unrelated anaerobic protists that can only be accomplished by combining distinct technology and organismal expertise.
2024
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Grant Awardees - Program Grants
Discovering the chemical space of bioactive modified nucleotides and their enzymatic repertoire
BELTRAO Pedro (SWITZERLAND)
- Swiss Federal Institute of Technology in Zurich (ETH Zurich/ETH Zürich) - Zurich - SWITZERLAND
CORREIA-MELO Clara (PORTUGAL)
- Leibniz Institute on Aging - Fritz Lipmann Institute e.V. - Jena - GERMANY
FUGGER Kasper (DENMARK)
- University College London Cancer Institute - London - United Kingdom
Nucleotides are basic molecules of life. A plethora of modified nucleotides (modNs) have been identified in DNA and RNA, with a few known to regulate gene expression, DNA repair, and neuronal activity. Yet, only few modNs have been identified as free monomeric nucleotides, i.e. not incorporated in nucleic acids, in nature. ModNs vary among species and exhibit diverse and striking bioactive properties such as base Z, a bacteriophage deoxynucleotide of prebiotic origin that defends against bacterial restriction enzymes, can self-repair DNA lesions and promotes read-through of stop codons in humans. Other modNs can potentiate chemotherapy or induce mutations, epigenetic changes or cytotoxic responses. To eliminate harmful modNs, species have evolved detoxifying enzymes that prevent the detrimental effects of their DNA incorporation. Despite the potential negative effects of misincorporation of bioactive modNs on organismal fitness, a systematic assessment of their chemical nature, biological sources, cross-species effects, and associated modifying and detoxifying enzymes is lacking. Here we propose a multidisciplinary approach, integrating advanced analytical chemistry, computational modeling and cell biology to: i) systematically identify and quantify modNs in human and gut microbial samples, ii) predict nucleotide modifying and detoxifying enzymes and their evolution and iii) characterize the physiological impact of identified modN on human cells, and validate the function of AI-predicted detoxifying enzymes. Undertaking this research will significantly expand our understanding of the identity, biological origins and impact of modNs, along with the evolutionary dynamics of modifying and detoxifying enzymes across the tree of life. Ultimately this research has far reaching implications from evolutionary biology to clinical therapies, whilst expanding our knowledge of chemical species-species interactions across domains of life.
2024
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Long-Term Fellowships - LTF
Neural mechanisms for dynamic action planning and execution as we move through space
BENCIVENGA Federica (ITALY)
Département de neurosciences - University of Montreal (Université de Montréal) - Montreal - CANADA
GREEN Andrea (Host supervisor)
CISEK Paul (Host supervisor)
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2024
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Long-Term Fellowships - LTF
Investigating the effects of chronic stress on gut-brain interactions
BIGLARI Nasim (GERMANY)
Bioelectronics Group - Massachusetts Institute of Technology - MIT - Cambridge - United States
ANIKEEVA Polina (Host supervisor)
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2024
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Cross Disciplinary Fellowships - CDF
Coupling massive gene synthesis with generative sequence models to decipher antibiotic resistance
BISARDI Matteo (ITALY)
Michael Smith Laboratories - University of British Columbia - Vancouver - CANADA
TOKURIKI Nobuhiko (Host supervisor)
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2024
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Grant Awardees - Early Career
Quantifying the 4-dimensional microenvironment to explain the coexistence of social insects
BISHOP Tom (United Kingdom)
- Cardiff University - Cardiff - United Kingdom
DAVIES Andrew (SOUTH AFRICA)
- President & Fellows of Harvard College - Cambridge - United States
JANION-SCHEEPERS Charlene (SOUTH AFRICA)
- University of Cape Town - Cape Town - SOUTH AFRICA
SENIOR Rebecca (United Kingdom)
- School of Biological & Biomedical Sciences, Durham University - Durham - United Kingdom
We seek to understand how microclimatic variation in 4D contributes to the coexistence of competing ant species. We will do this by integrating high-resolution environmental, topographic, physiological, and behavioural data from the diverse South African Karoo ecosystem using a combination of techniques that the research team has developed and pioneered.
Few places on Earth are dominated by a single species, instead, most are rich mosaics of coexisting species. Traditionally, coexistence has been explained by niche differentiation and the different resource requirements of species. Many species, however, coexist despite their similar requirements and alternative hypotheses are needed to explain, predict, and understand their coexistence patterns.
We propose a simple, yet untested, explanation for the coexistence of diverse ecological communities: the microclimate-maze hypothesis. This hypothesis posits that climatic variability at the micro-scale effectively isolates individuals and species from each other within a landscape. This isolation prevents competition and promotes coexistence. The microclimate-maze is a simple idea, but the high-resolution, spatiotemporally explicit environmental and biological data required to test it is challenging to obtain.
Here, the complementary expertise of our team will test the microclimate-maze hypothesis relative to classic coexistence theories across five subprojects:
- First, we will empirically measure the microclimate across sixteen 0.25 ha plots in the South African Karoo.
- Second, we will generate high-resolution, 4D maps of microclimate by combining the empirical data with drone-based LiDAR via heat and vapour transfer equations.
- Third, we will rapidly estimate the physiological thermal and hydric performances of over 40 different ant species using novel infrared detection methods.
- Fourth, we will intensively monitor the nesting, foraging, and dietary preferences of ants living in the study plots.
- Finally, we will combine these data in a spatiotemporally explicit framework to test the microclimate-maze hypothesis.
A greater understanding of how species coexist in the same landscapes is a fundamental goal of biological science and will be crucial to understanding when, if, and why ecosystems change in response to environmental fluctuations.
2024
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Long-Term Fellowships - LTF
Structural basis of the human spliceosome quality control
BOREIKAITE Vytaute (LITHUANIA)
Plaschka group - Research Institute of Molecular Pathology (Forschungsinstitut f molekulare Pathologie GesmbH, IMP) - Vienna - AUSTRIA
PLASCHKA Clemens (Host supervisor)
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2024
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Grant Awardees - Program Grants
Probing the evolutionary ecology of cognition through High-Density Diffuse Optical Tomography
BOTERO Carlos (United States)
- The University of Texas at Austin - Austin - United States
CULVER Joseph (United States)
- Washington University in St.Louis - St. Louis - United States
GÜNTÜRKÜN Onur (GERMANY)
- Ruhr University Bochum (Ruhr-Universität Bochum) - Bochum - GERMANY
How did advanced cognition and general intelligence evolve? This fundamental question remains largely unanswered because brain anatomy and function have only been studied in a surprisingly small number of species. Recent advances in imaging technology have enabled the characterisation of individual patterns of brain functional connectivity creating a new opportunity for comparing across species and studying the evolution of cognition. However, existing tools like fMRI are expensive, non-portable and tend to require sedation (which disrupts neural networks). This project will bridge these critical gaps by developing a portable, cost-effective optical tool for imaging awake whole-brain functional connectivity in birds and using this groundbreaking tool to study how the architecture and properties of neural networks (i.e., the blueprints of cognition) vary in relation to morphology, ecology, and behaviour. Our research plan involves: (1) Transferring existing Diffuse Optical Tomography (DOT) technology from mammals to birds and validating the performance of these instruments with existing connectivity data on pigeons, advanced computational simulations, and parallel fMRI studies; (2) Developing advanced algorithms for processing, characterising, and comparing functional connectivity networks to ensure the robustness and accuracy of large scale interspecific comparisons; and (3) Applying our new imaging technology to study functional connectivity differences in four major avian clades with well-known differences in ecology and cognitive ability to demonstrate the feasibility of our approach. The successful completion of these goals will transform the eco-evolutionary study of cognition by enabling the characterisation of functional connectivity patterns in large numbers of species over relatively short timescales. Additionally, it will represent a major step forward in the fields of evolutionary neuroscience, cognitive ecology, and cognitive psychology by enabling a shift in focus from comparing singular brain regions to comparing the complex neural networks that actually drive cognitive functions. In terms of brain imaging, this project will also deliver critical improvements to our ability to sample functional connectivity repeatedly, non-invasively, and in the wild at a fraction of current costs.
2024
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Long-Term Fellowships - LTF
Protein dynamics and function in the evolutionary history of the CO2 fixing enzyme Rubisco
BUCHANAN Charles (UK)
Evolutionary Biochemistry - Max Planck Institute for Terrestrial Microbiology - Marburg - GERMANY
HOCHBERG Georg (Host supervisor)
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2024
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Grant Awardees - Program Grants
Deciphering the role of ion distribution in mitochondria for long-term memory formation
BUSCH Karin (GERMANY)
- University of Münster (Westfälische Wilhelms-Universität Münster) - Muenster - GERMANY
JONAS Elizabeth (United States)
- Yale University - New Haven - United States
TOMKINSON Nicholas (United Kingdom)
- University of Strathclyde - Glasgow - United Kingdom
Long-term potentiation (LTP; memory formation) involves stimulation of neurons and enlargement of specific synapses. Surprisingly, LTP requires an increase in metabolic efficiency (an increase in ATP produced/oxygen molecules consumed). Mitochondrial energy metabolism is controlled by the proton motive force (PMF) across the inner mitochondrial membrane (IMM), which drives ATP synthesis. The PMF consists of an electrochemical gradient, but its exact ionic composition is not known. Furthermore, the IMM is not absolutely tight for ions but shows a certain conductance. We hypothesize that an increase in metabolic efficiency to provide ATP for LTP is based on an optimization of usage of PMF. We propose two mechanisms: a) structural alteration in cristae compartments that optimize the PMF usage and OXPHOS coupling and b) a decrease of the leakiness of the IMM for ions, e.g. through closure of a large ion channel contained within the ATP synthase c-subunit ring. We suggest that this closure is due to an internal conformational change that includes the reorganization and movement of ATP synthase F1 toward FO resulting in ATP synthesis onset and thus an increase in ATP production efficiency. To test this hypothesis, structural changes of the IMM as well as dynamic ion distributions on both sites of the IMM before and after LTP will be determined. N. Tomkinson will design and synthesize bioanalytical fluorescent sensors for monovalent and divalent ions (H+, Ca2+, K+, Na+) and test them first in HEK-293 cells. Suitable IonS will then be used in neurons to record potential changes across the IMM. To place the sensors accordingly, they will be chemically conjugated to substrates of self-labeling tags, such as the Halo-tag. These so-called ion sensor HaloTag ligands (IonS-HTL) are used by K. Busch and E. Jonas to dope Halo-tagged proteins in the intracristae space and matrix of neurons to monitor changes in ion concentrations due to LTP. To account for ultrastructural changes and reorganization of ATP synthase during LTP, K. Busch and E. Jonas will conduct high resolution imaging using cristae specific dyes and Halo-tagged ATP synthase for single molecule tracking and localization. This will allow us to test whether increased efficiency in ATP synthesis after LTP stimulation is due to a reorganization of ATP synthase, leak closure and/or changes in the cristae structure.
2024
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Grant Awardees - Program Grants
3D-bioprinting meets machine learning: a novel tool to decipher the determinants of viral tropism.
CASTRILLO Gabriel (SPAIN)
- University of Nottingham - Nottingham - United Kingdom
STEGMAYER Georgina (ARGENTINA)
- National University of the Littoral (Universidad Nacional del Litoral, UNL) - Santa Fe Capital - ARGENTINA
VALLI Adrian (ARGENTINA)
- Spanish National Research Council (Consejo Superior de Investigaciones Científicas, CSIC) - Madrid - SPAIN
Similar to humans, plants can be infected with a variety of viruses producing diseases, including plant death. These infection outcomes are determined by the viral tropism, the specificity of a virus for a cell type, tissue or species. This unique virus characteristic is regulated by the host immune system, the site of entry, and the cell types infected. Thus, knowing determinants of viral tropism is critical to predict and control the spreading of a viral infection and its outcome. In humans, this information is available for a high number of viruses because of the existence of novel tissue and organ models, like organoids, that facilitate the generation of this knowledge. Unfortunately, in plants similar technologies have not yet been developed, slowing down the study of viral tropism and the design of novel strategies to tackle virus infection. With this project, we will take a major step to correct this oversight by deciphering why a virus can colonise a cell type and not others. This is achievable now because we have a unique multidisciplinary team composed by experts in plant sciences, biomaterials, virology, imaging and machine learning methods from four different countries. This team will collaborate to demonstrate our hypothesis that similar to human organoid models, it is possible to reproduce plant organ characteristics in vitro to develop organ models to study viral tropism. We will do this via an innovative approach that includes the use of novel self-assembling materials combined with key macromolecules and living cells from the different plant organs (leaf, stem, and root) that enable 3D-printing of artificial plant organ tissues (objective 1). These models, that reproduce 3D characteristics of different plant tissues will be infected with a collection of labelled viruses to study viral tropism. So, we will know which cell types from each organ can be colonised by a virus and which genes they induce (Objective 2). This data will be used to predict the viral ability to colonise intact plant tissues via machine learning methods and will be validated in real plants (Objective 3). This technology will open new avenues to understand the impact of viral tropism on plant health, a central aspect of all crop breeding programs and will help us design novel antiviral strategies to increase crop performance under current and future climate conditions.
2024
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Grant Awardees - Early Career
How predictable is evolution? Eco-evolutionary dynamics of fungi across biological scales
CHARLEBOIS Daniel (CANADA)
- University of Alberta - Edmonton - CANADA
MANHART Michael (United States)
- Rutgers Biomedical and Health Sciences - Newark - United States
WORTEL Meike (NETHERLANDS)
- University of Amsterdam - Amsterdam - NETHERLANDS
Evolutionary biology has traditionally focused retrospectively on the natural history of life, but new tools and challenges (such as climate change and drug resistance) have precipitated the need for evolution to become a predictive science. The repeatability of evolutionary processes is a key concept for making these predictions. While previous studies have uncovered some of the basic theory and examples of repeatable evolution in single-species microbial populations, it is not clear what these results mean for repeatability in multispecies communities where microbes naturally exist. Furthermore, the relationship between species diversity and repeatability may depend on the biological scale we consider, but we lack general principles for how evolutionary repeatability varies across scales.
We have assembled an interdisciplinary team, combining experiments on communities of Candida yeast (led by DC), multiscale modeling (led by MW), and bioinformatics/theory (led by MM), to address how eco-evolutionary feedbacks affect evolutionary repeatability across biological scales. The main hypothesis of our project is that greater species diversity decreases evolutionary repeatability. Candida yeasts are an ideal system to address this hypothesis, as Candida naturally occur in multispecies communities and rapidly evolve resistance to antifungal drugs. The project is structured into four interconnected objectives, each involving collaborations between PIs. We will empirically (Objective 1) and computationally (Objective 2) explore how antifungal resistance is affected by communities, ploidy, and drug concentrations. Empirical data will inform multiscale models (including genotypes, phenotypes, and environment) and model predictions will be verified by experiments. These models (Objective 2) will then inform conditions for evolution experiments (Objective 3) and produce evolutionary simulations to test repeatability across interspecies diversity. Both the empirical and computational evolutionary outcomes will be analyzed with a novel framework to quantify repeatability across biological scales (Objective 4), and hypotheses about the underlying mechanisms will be validated in simulations (Objective 2). Altogether this project will make a fundamental advance toward evolutionary predictions of microbes in ecologically-relevant environments.
2024
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Long-Term Fellowships - LTF
Targeted epigenome editing using induced proximity-based small molecules
CHIBA Kosuke (JAPAN)
Department of Chemistry, Department of Molecular and Cell Biology - The Regents of the University of California, Berkeley - Berkeley - United States
NOMURA Daniel (Host supervisor)
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2024
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Grant Awardees - Program Grants
Unambiguous Biosignatures for Life Detection
CLEAVES Henderson (United States)
- Howard University - Washington - United States
MCMAHON Sean (United Kingdom)
- University of Edinburgh - Edinburgh - United Kingdom
VAN ZUILEN Mark (FRANCE)
- French National Centre for Scientific Research (Centre national de la recherche scientifique,CNRS) - Plouzané - FRANCE
What distinguishes living from non-living matter? Organisms (and their fossil and otherwise degraded remains) differ from non-biological entities in important ways. It is particularly notable that natural selection favors certain materials, morphologies, and metabolic processes, which have evolved many times independently, likely because they represent “optimality peaks” on the landscape of evolutionary fitness and because these peaks may be (onto)genetically accessible from multiple starting points and evolutionary histories. We propose to apply state of the art machine-learning methods and analytical tools from paleontology and organic geochemistry to discriminate biological and non-biological materials, patterns and processes. Our first major goal is to improve our ability to recognize proxies for life (“biosignatures”) in environments far removed from us in time (e.g. billions of years old terrestrial samples), in space (e.g. in extraterrestrial solar system materials), or in physicochemical conditions (extreme environments on the modern Earth). Our second goal is to address the question of how and why biological materials differ systematically from non-living ones. This aligns with HFSPO’s mission “to fund basic research focused on the elucidation of the sophisticated and complex mechanisms of living organisms”.
2024
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Grant Awardees - Program Grants
Optogenetic control of organelle “chatter” and effects on calcium dynamics in human cardiomyocytes
COLMAN Michael (United Kingdom)
- The University of Leeds - Leeds - United Kingdom
ENTCHEVA Emilia (United States)
- The George Washington University - Washington - United States
SATO Moritoshi (JAPAN)
- The University of Tokyo - Tokyo - JAPAN
Excitation-contraction coupling (ECC), linking electrical events to calcium release and mechanical contraction, is central to the heart’s function. Current ECC theories focus on the sarcoplasmic reticulum, SR, as the main intracellular calcium store with optimized location and molecular makeup for reliable calcium cycling to translate electrical triggers into mechanical work. As highly metabolically active cells, cardiomyocytes have a densely populated and intricately structured cytosol, full of organelles with their own calcium cycling machinery. These non-SR organelles include the mitochondria, lysosomes, endoplasmic reticulum (ER). Recent imaging data suggest proximity and possibility for communication (“chatter”) between these organelles in synchronizing calcium release via nanospaces. To fill a gap in our understanding of the contribution of non-SR compartments to cardiac ECC, we will develop and deploy new cardiomyocyte-tailored optogenetic “magnet” tools to dynamically bring organelles together while tracking calcium release and wave dynamics. Human pluripotent stem cell derived cardiomyocytes, iPSC-CMs, will serve as an experimental model for this project. Effectiveness of tethering of different organelles by light will be assessed using fluorescence reporter co-localization, as well as optogenetics-enabled fast-freezing electron microscopy of ultrastructure. The functional consequences of light-induced nanodomains between key calcium stores and increased “chatter” between them will be systematically quantified by voltage and calcium dynamics measurements using global and organelle-specific optical sensors. These experimental observations will be used to formulate new inclusive models of ECC that reflect organelle proximity and “chatter” to better capture pathological states and to potentially provide new anti-arrhythmic therapeutic options. Some organelle tethering will also aim to induce a more mature state in the iPSC-CMs, i.e. compensate for the lack of T-tubules or initiate T-tubule formation by light for enhanced ECC. Overall, this interdisciplinary work will contribute to our fundamental understanding of calcium dynamics in the heart, by providing an updated quantitative view of ECC including non-SR compartments.