Cornell University

NSF Awards · FY 2025 · 2025-04

Geohazards pose large risks at geologically active continental margins. These geohazards are interconnected and thus difficult to study in isolation. The goal of this project is to bring together experts to develop plans for an integrated array of instruments to observe these hazards. The array will be designed using Chile as a case study. This is a unique location where frequent events and existing networks provide a global understanding of interacting hazards. Teams of experts in computer modeling and technical planning will design sub-arrays for earthquake, volcanic, and landslide observations. Teams will also compile new catalogs of earthquakes and landslide susceptibility in the study area. The teams will meet in a 3-day workshop to synthesize results. Broad input from the scientific community will be solicited through a series of webinars. New models and catalogs will be shared openly through the SZ4D website and data repositories to benefit communities exposed to subduction-related hazards in the U.S. and internationally. Subduction of ocean lithosphere results in the largest earthquakes, volcanic activity, and landscapes highly prone to destructive landslides. For decades research related to subduction and related geohazards has proceeded piecemeal. This research will provide the basis for an overarching framework for integrated studies that can directly address the linkages between earthquake, volcano, tsunami, and landslide geohazards. This award will support a series of modeling studies and technical planning that will be used to design three overlapping arrays of instrumentation at the Chile Subduction Zone. Chile is unique in combining a high level of geological activity and good logistical access. The instrument array will be designed to observe a broad range of earthquake, volcanic, and landslide processes. The work is organized into ten work packages. Five will assess and plan various aspects of the seismic detection and geodetic network. Two will address sediment and hydrologic transport for landslides. Two will address using seismicity to forecast volcanic processes. The final work package will bring together the others with a three-day workshop and with scientific community input via a series of webinars. The connection between this research and the SZ4D initiative makes very clear the connection of this planning activity to benefit people who live with subduction-related geohazards in the U.S. and globally. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-04

This project designs and studies informal engineering learning resources that support families with young children (ages 6–10) in engaging in hands-on engineering activities at home. The resources span biological, civil, computer, electrical, environmental, and mechanical engineering and introduce children to core engineering practices, including empathy, problem definition, solution ideation, prototyping, and testing. Through a co-design process with families, the project aims to create developmentally appropriate, accessible learning experiences that support early engagement with engineering concepts and practices. Caregiver-focused video workshops will accompany the materials to support adults in facilitating meaningful at-home engineering learning. The research examines how structured, family-based learning experiences influence children’s interest, confidence, and engagement in engineering-related problem-solving. Project deliverables include a suite of easy-to-implement engineering modules and instructional videos designed for broad use in informal learning settings. These resources will be disseminated through national homeschooling networks, public media outlets, widely used engineering lesson repositories, and professional STEM education networks to ensure broad access and scalability. Using a mixed-methods research design, the study will analyze data from pre- and post-engagement surveys, recordings of caregiver–child interactions, interviews, caregiver reflective journals, and child-generated artifacts such as sketches and design outputs. Analyses will generate evidence-based insights into how informal learning environments can support early engagement with engineering and understanding of engineering practices in everyday contexts. Findings will be disseminated through scholarly journals, professional conferences, and educational networks to inform research and practice in informal STEM education. By strengthening early exposure to engineering practices and problem-solving skills, this project contributes to public scientific literacy, STEM workforce development, and broader participation in engineering learning pathways. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-03

Correct use and interpretation of communication signals between individuals can determine the consequences of aggressive interactions, including the potential to win a fight or to avoid unnecessary escalation of aggression resulting in physical injury. How does the brain allow individuals to actively control signaling behaviors appropriate to different social contexts? Danionella fishes are among the smallest adult vertebrates (fishes, amphibians, reptiles, birds, mammals) and are transparent throughout their lifetime. These qualities give unprecedented access to the entire brain, not yet possible in any other vertebrate. Leveraging Danionella’s relatively simple, highly stereotyped and readily measurable acoustic and postural displays produced only during aggression, the investigators of this project investigate how the adult vertebrate brain regulates communication during aggression. Cellular and molecular methods are used to identify neurons activated during aggressive interactions in brain regions (cerebral hemispheres, hypothalamus) that together are proposed to be comparable to a core aggression system in mammals. Artificial intelligence-based methods are used to quantify adult posture and movements during aggression. This approach provides a rigorous analytical framework with which to evaluate the behavioral effects of neuroimaging-guided, laser-induced disruptions to individual brain regions comprising the proposed core aggression circuit. The new model for behavioral neuroscience used in this project thus presents a unique opportunity for identifying and understanding brain networks activated in adults during social interactions and, more specifically, during aggression. The project also includes activities aimed at transferring knowledge via interactive public events, and to provide interdisciplinary training and education to individuals at different career stages. Understanding how forebrain neuronal networks (e.g., preoptic area, hypothalamus) control the output of downstream motor-patterning circuitry in the midbrain remains central to understanding how the brain enables individuals to select and sequence different patterns of behavior. Social communication behaviors in fishes are particularly tractable models for addressing this challenge. Their behaviors are often highly stereotyped, differ in a finite set of easily quantified features, and depend on precise patterns of neural activation. Recent studies effectively demonstrate that miniature, transparent species of Danionella fishes, which are among the smallest living adult vertebrates, provide particularly tractable models for uncovering principles of neuro-behavioral mechanisms applicable to all vertebrates. Unlike the closely-related zebrafish, which are neither naturally transparent nor miniature as adults, Danionella adults make robust acoustic and postural displays that are often closely linked in timing during aggressive interactions. Aim 1 of this proposal seeks to map a forebrain aggression network that is activated in Danionella during multimodal displays and identify its neurochemical phenotypes. Aim 2 involves use of laser ablations of select forebrain sites identified in Aim 1 to test the predictions of a model, informed by artificial intelligence-based quantitative analysis of acoustic, postural, and jaw extension displays, about the forebrain’s role in driving acoustic and postural behaviors. These aims offer unprecedented opportunities to establish Danionella as a model to guide brain-wide optical and genetic studies of neural circuits underlying adult vertebrate aggression. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-03

As a field, engineering education has focused significant effort on overcoming barriers to change, often through solutions requiring high levels of administrative and financial support. While achieving impact, these solutions have the potential to miss the hundreds of departments and institutions that do not have access to these same resources. Further, the field’s focus on specific barriers has overshadowed existing change approaches among educators in resource-limited contexts. The stories of these educators are rarely amplified, even though they present an opportunity to explore alternative approaches to change and understand the specific strategic actions these individuals take to impact change. With that in mind, this CAREER project aims to develop visible examples of alternative approaches to curricular transformation and co-design interventions (e.g., workshops, activities, resources) that will be led and disseminated by engineering educators in their own departmental, institutional, and disciplinary communities. By examining and making these alternative approaches visible, this work will complement and work synergistically with the existing research examining barriers to educational change, large-scale collaborative change efforts, and engineering education faculty development. Overall, the results of this CAREER project will advance knowledge by articulating the individual, structural and cultural supports and barriers for impacting course and curricular transformation that can be used by faculty and graduate student developers, administrators, and funding agencies. This CAREER award will leverage the positive deviance approach, which is an asset-based and participatory approach to change. The three-phase integrated research and education plan builds on the core tenants of the approach: a recognition that solutions already exist within the engineering education community, partnerships with community members to discover possible solutions, and a central focus on assets (as opposed to barriers and constraints). In particular, the research plan is grounded in theories of professional agency and designed to co-construct an understanding of how to foster agency toward curricular change by exploring the experiences and pathways of engineering educators who have overcome pedagogical inertia. In the first phase, a survey of engineering educators will provide a foundational understanding of the distinguishing and unifying characteristics among faculty pursuing curricular transformation. From the results of this survey, educators that have successfully developed transformational curricular designs while facing barriers that have impeded change in other contexts will be recruited for participation in Phase 2a. Phase 2a will be focused on a multiple case study examining three data sources (i.e., in-depth interviews, observations of course sessions, and curricular-change-related documents). These data sources will be analyzed using narrative analysis methodologies to create in-depth change stories of these educators (n=12-15). The research and education plans will be integrated within Phase 2b through a collaborative inquiry of engineering educators (n=8-12) who want to pursue curricular transformation work. The outcomes of this collaborative inquiry will be community validation of the change stories and educator-led dissemination and propagation activity designs. The educator participants will lead the dissemination of these activities to their disciplinary, departmental, and institutional communities. The final phase captures the education plan and will include activities each year of the project. This third phase will seek to make change visible by developing a professional learning framework for courses and workshops on educational change, enabling educator-led dissemination to their communities, and amplifying the change stories through multiple mediums. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-03

The emergence of novel traits – traits that are unique to a group of organisms – is an important driver of organismal diversity, yet our understanding of how novel traits arise is still in its infancy. Nematocytes, the stinging cells found only in cnidarians (corals, jellyfish, and their relatives), are an important model for understanding the origin of novelty. Nematocytes derive their sting from their ability to eject a tiny, venom-laden harpoon from a pressurized compartment inside a cell. The compartment, and the harpoon it contains, are constructed of an unusual protein called minicollagen, which is also found only in cnidarians. Recent advances in genome sequencing have greatly improved our ability to detect novel protein-coding sequences from DNA; still, there remains a critical gap in our understanding of how novel proteins (like minicollagen) give rise to novel traits (like the nematocyte). To address this gap, the proposed work is characterizing the protein-protein interactions necessary for the development of the stinging apparatus in diverse types of nematocytes. Additionally, to understand how novel protein-coding sequences acquire adaptive functions, this work is investigating the processes that direct proteins to their proper locations inside the cell. Ultimately, these investigations will enable the development of designer cells with traits that have never come together naturally. The educational goal of this research is to better prepare undergraduate students to pursue careers in integrative research through development of a research-based lab course in evolutionary cell biology. This research is also increasing public science literacy by providing new and innovative learning resources to STEM educators and museum visitors. The overarching goal of this work is to develop a framework for predicting the emergence of novel traits from novel protein-coding genes by investigating the processes that drove the emergence of the nematocyte. To achieve this goal, the proposed work is using mass spectroscopy and proteomic analysis to characterize how unique nematocyte types emerge from taxon-specific interactions among novel proteins (Aim 1). Additionally, using genome engineering to alter protein localization, the proposed work is reconstructing the order of events that permitted the fixation of the nematocyte-specific protein minicollagen in the stem cnidarian genome (Aim 2). Collectively, this work is revealing how functional interactions among novel proteins drive the emergence of novel traits. This work will advance our ability to predict the fate of novel proteins and contribute significantly to explaining cases of novelty that arise de novo from new genes. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2025-03

Project Summary/Abstract The elimination of existing neuronal structures by phagocytes is essential for the development and maintenance of a functional nervous system but can also drive neurodegeneration. Although an “eat-me” signal, phosphatidylserine (PS), is known to mark neuronal structures for engulfment, how PS is detected by endogenous sensors to activate phagocytes and how the recognition of PS exposed at axon terminals affect the maintenance of synapses remains poorly understood. The goal of this proposal is to address these fundamental questions using our unique in vivo models in Drosophila. Answering these questions is an important step towards understanding how phagocytes interact with neurons to regulate the development, maintenance, and degeneration of the nervous system. Orion, a chemokine-like secreted protein in Drosophila, was recently found to be an in vivo PS sensor that bridges interactions between PS on degenerating neurons and the conserved engulfment receptor Draper on phagocytes. Although the Orion expression level correlates with phagocyte potency, how Orion enables Draper to detect PS-exposing neurons and modulates phagocyte sensitivity is unknown. In addition, preliminary studies reveal that the Drosophila neuromuscular junction displays PS exposure on synaptic boutons and synapse-derived extracellular vesicles (EVs). This proposal aims to determine the molecular mechanism by which PS sensing regulates phagocyte activation and the significance of PS recognition at the NMJ. To achieve these goals, the following three aims are proposed: 1) Determine how Draper/PS interaction is mediated by the PS sensor during engulfment of neurons. Orion sequences that interact with PS and Draper will be mapped using in vitro biochemical assays, in vivo degeneration assays, and in vivo targeted mutagenesis screens. PS-binding properties of similar human chemokines will be examined using in vivo assays in Drosophila. 2) Elucidate the molecular basis of phagocyte sensitivity to PS exposed on neurons. The effects of heparan sulfate proteoglycans (HSPGs) and phagocyte PS exposure on Orion activity and phagocyte sensitivity will be examined. 3) Reveal the role of PS exposure and sensing in the maintenance of Drosophila NMJs. The PS-exposing sites on synaptic boutons will first be precisely mapped by volume electron microscopy (vEM) and 3D reconstruction of entire NMJs. The effects of perturbing PS exposure at the NMJ and the role of Orion in the biogenesis, transmission, and disposal of axon- derived EVs will be examined. Lastly, candidate scramblases will be tested for possible involvements in NMJ PS exposure. Together, these aims will reveal mechanistic insights into PS sensing in the nervous system for understanding how PS exposure is related to the maintenance of neuronal connections and to neurodegenerative diseases.

NIH Research Projects · FY 2026 · 2025-03

ABSTRACT Tweety Homologues (TTYH1-3) comprise a unique family of membrane proteins that are highly expressed in the nervous system. Knockout studies in mice demonstrate that these proteins play important roles in neurogenesis, nociception, and brain development. The cryogenic electron microscopy (cryo-EM) structures of mammalian TTYH1-3 have revealed that they form homodimers with a unique fold, distinct from any structures currently available in the database. However, the molecular functions of these membrane proteins remain unclear. Without knowing how TTYHs function, it remains challenging to target this important class of membrane proteins for potential new treatments for various neurological diseases. The long-term goal is to elucidate the mechanism by which TTYH family membrane proteins mediate crucial physiological and pathological events in the nervous system. The specific objectives for this application are to uncover a non- homodimeric configuration of TTYH and to explore the role of this membrane protein in neurodevelopment and regeneration. The central hypothesis is that TTYH forms a complex with another membrane protein to transduce extracellular cues into intracellular signals for neurite outgrowth. The rationale for the proposed research is that by uncovering a new configuration, the mechanistic understanding of how TTYH operates will improve, moving beyond the limitations of the currently available homodimeric structures. In addition, establishing its role in neurodevelopment and regeneration will enable us to fill in the critical gap in understanding how malfunctioning TTYH can cause diverse neurological diseases. The central hypothesis will be tested by performing two specific aims: 1) Uncover the heteromultimeric configuration of TTYH using biochemical and cryo-EM approaches, and 2) Determine whether TTYH mediates neurodevelopment and regeneration using live imaging and laser ablation in transgenic worms. The proposed research is innovative because it intends to provide the first near-atomic resolution structure of TTYH in complex with an interacting partner discovered from endogenously expressed protein. It is also innovative because it will take advantage of C. elegans, a powerful model organism for studying neurodevelopment and neurogenesis, on TTYH for the first time. The contribution of the proposed research is significant because it will provide crucial new insights into the unforeseen heteromultimerization and specific function of this unique class of membrane proteins in the nervous system. These efforts represent an important initial step toward understanding what this family of membrane proteins do, why they are highly expressed in the nervous system, and how they mediate reported pathophysiological activities.

NSF Awards · FY 2025 · 2025-03

Authenticated encryption with associated data (AEAD) is by now the standard way in which computing systems use cryptography to protect data. As such, secure and high-performance AEAD is critical to protecting society's digital infrastructure. Recent work has shown how the AEAD design paradigms underlying our mostly widely used encryption schemes are vulnerable to attacks in important applications. Widely used schemes also do not provide the performance required of modern large-scale cloud services. There is now widespread agreement that the technology industry needs a new generation of AEAD schemes, to ensure the security of our digital systems in the coming decades. In this project, the team of researchers will pursue a research agenda aimed at laying foundations for the next generation of AEAD schemes. It will generate new, foundational theory to yield principled AEAD design paradigms that will rectify the security issues and performance limitations of current schemes. Doing so will involve new measurement studies, articulation of flexible AEAD as a design goal, new techniques for building schemes, and new deployment patterns realized via public, open-source libraries. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-02

This award supports a research program to study the physics of a turbulent plasma in the laboratory. Turbulence exists in the fluids that we experience every day. The unpredictability of turbulence limits our forecasting ability for everything from weather to air travel. Turbulence also exists in plasmas - the hot, ionized gases that make up most of the visible Universe. Plasma turbulence plays an important role in a wide range of astrophysical phenomena, from black hole accretion disks to the interstellar medium, where the heating from turbulence enables the formation of organic molecules which are the building blocks of life. Plasma turbulence also limits the performance of potential future fusion energy reactors. This research program will develop a new platform for producing turbulent plasma in the laboratory and new methods for measuring plasma turbulence. The award also supports a substantial effort to develop an open-access plasma laboratory class, which includes designing, building, and testing laboratory experiments that can be easily reproduced by other instructors. If successful, this effort will strengthen the US STEM workforce by spreading plasma physics instruction to a broader range of educational institutions. Just as hydrodynamic turbulence is built from vortices of fluid motions, magnetized plasma turbulence is built from magnetic islands and current sheets, which serve to transfer the magnetic energy between different spatial scales. This project will use an imploding carbon wire-array Z-pinch, driven by the new PUFFIN generator at the Massachusetts Institute of Technology, as a magnetic island merging platform to generate magnetized plasma turbulence. This magnetized plasma turbulence will be in a previously unexplored regime: sustained, highly collisional, with an ion-skin depth between the driving and dissipative scales, and energy approximately equipartitioned between magnetic, thermal, and kinetic. Advanced diagnostics, such as Faraday rotation imaging, Thomson scattering, and imaging refractometry, will be used to study the transition from a laminar to a turbulent plasma. The diagnostics will serve to characterize the evolution of the power-spectrum and intermittent structures above and below the ion skin depth, and the role of an imposed or self-generated mean-field in correlating turbulent structures. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-02

Both earthquakes and ice sheet collapse pose enormous hazards with severe societal consequences. Both systems are partly controlled by friction. Microscopic contacts at rock interfaces of the fault or the base of the ice sheet controls the friction in these systems. The details of how these surfaces evolve as rocks fail hold information to better understand future events and to assess hazards. It is impossible to observe these interfaces in nature. The most informative measurements come from sensors placed at the surface. The goal of this proposal is to instead observe an experimental system to determine how interfaces slip and evolve. The experiments listen to ice slip experiments with sensors to study how the faults evolve, and how changes may affect seismic hazards. The project will support a graduate student and a collaboration across three institutions. The goal of the study is to understand how the evolution of contacts during cycles of shear, slip, and stability control large scale behaviors in both faults and glacial systems. This will be accomplished by directly observing the coupled processes that control nucleation, slow and fast slip, healing, drag, and melting in ice to understand the fundamental mechanisms that drive the evolution of conditionally unstable frictional interfaces. A series of both static and sliding experiments will be performed using a custom cryogenic biaxial apparatus and a sample of ice atop a glass plate. Ice will be used for two key reasons: 1) it is transparent, allowing light and images to be transmitted through it; and 2) it has a low melting temperature, such that exploring a modest range of temperature covers a broad swath of homologous temperature, T/Tm, and thus both brittle and ductile behavior. This knowledge, analyzed by cutting-edge machine learning data analysis methods and extrapolated up to larger systems, will improve understanding of the mechanics of the entire stick-slip cycle and stability. The project will support a graduate student and a collaboration across three institutions. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-02

The work aims to support U.S.-based early career researchers to attend a 5-day conference set to occur between 24-28 March 2025 in Cambridge, U.K. This conference is part of a special joint international workshop efforts to sharing the latest results from three ongoing model inter-comparison projects organized through a core project of the World Climate Research Program called the Atmospheric Processes And their Role in Climate. The workshop aims to help participants better understand the role of the stratospheric processes in enhancing weather, climate, and extreme events. Emerging outcomes may lead to the improvement of sub-seasonal-to-seasonal predictions and climate projections which would have strong societal benefits. The involvement of the supported early career researchers can contribute to the development of future leaders in the fields of Science, Technology, Engineering, and Mathematics and an effective national workforce. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-02

Grapevines are among the most economically important berries in the world. As a long-lived (perennial) crop, grapevines are typically cultivated as a clonally propagated stem (the scion) which is mechanically grafted to a genetically distinct, clonally propagated root (the rootstock). Because grapevines are cultivated as clones, individual plants of the same variety are essentially genetic twins. Thousands of clonal stem varieties are planted across the globe and exhibit large variation in growth, berry chemistry, and wine volatiles based on vineyard environmental conditions and management. This variation in growth and performance is known as phenotypic plasticity and impacts both fruit and wine characteristics, a phenomenon known culturally and commercially as ‘terroir’, the signature of the local environment on the vine. Because of their clonal nature, one potential mechanism contributing to phenotypic plasticity in grapevines is changes to the epigenome, a collective term for non-genetic DNA modifications that can change how specific genes and gene pathways are activated or deactivated. The goal of this project is to understand which portions of the grapevine genome are impacted by epigenetic changes, how epigenetic change in the root and the stem interact in grafted plants, and how these changes contribute to optimal plant resilience in response to environmental stress. These results will be used to help plant breeders identify the next generation of elite grapevine varieties and grape growers improve grapevine production across diverse growing regions. Integrated education and outreach include providing research training for project personnel in collaboration with industry partners across six states. In addition, project participants will be involved in outreach and hands-on research training activities that leverage existing programs and partnerships to maximize STEM participation of high school and undergraduate students. How do long-lived plants (perennials) acclimate to different environments and what is the extent of phenotypic plasticity possible from a single genome? Grapevines are grown as a composite of a clonally propagated stem (the scion) mechanically grafted to a clonally propagated root (the rootstock). These unique combinations of shoot and root are planted across diverse geographic regions around the world; consequently, grapevines offer a powerful system for investigating the molecular basis of whole-plant, multi-year phenotypic plasticity and enables the experiment disentanglement of the shoot genotype x root genotype x environment interactions across diverse climatic conditions. The goal of this collaborative project is to develop an integrated understanding of how the genome of clonally propagated perennial plants produces “adapted” phenotypes, from roots to shoots, over time and under different environmental conditions, and to identify the molecular basis of this phenotypic plasticity. This study will use experimental vineyards planted with a single scion cultivar ‘Marquette’ grafted to three commercial rootstock cultivars, replicated in three different environments (New York, Missouri, South Dakota). The project will use an integrative systems biology approach combining measures of plant physiology, leaf ionomics and metabolomics, fruit ionomics and metabolomics, wine chemistry analysis, and connections between sRNA, mRNA, and cytosine methylation signatures in shoots and roots across sites and their interaction with the spatial and temporal changes that occur in the epigenome in clonal shoots and roots. All data will be made accessible to the public through long-term repositories. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-02

2440352 (MacMartin). Climate change is already bringing damages to the US and elsewhere, and these will continue to get worse with continued emissions of CO2 and other greenhouse gases. Even with efforts to reduce emissions, there will still be significant impacts, both economic and human, resulting from future climate change. An additional option that could potentially reduce many climate damages is to cool the planet by reflecting a tiny bit more sunlight back to space. However, there is not yet sufficient information to support informed decisions. The two ideas most often suggested are Marine Cloud Brightening (MCB, the main focus of this work) and Stratospheric Aerosol Intervention (SAI). MCB would involve spraying sea salt aerosols into low clouds over the ocean to increase (force) cloud reflectivity, providing local and global cooling. The regional climate effects and associated impacts of MCB would depend quite strongly on where and how much forcing is applied, suggesting the potential to design an MCB approach to achieve multiple climate objectives. While there has been similar research conducted for SAI, there has been much more limited work treating MCB as a design problem. This project first aims to fill this gap, designing an MCB strategy to simultaneously manage multiple climate objectives by tuning the amount of forcing in different regions. This is an essential step towards assessing the climate impacts of MCB, and thus evaluating what role it might play in managing future climate risks. Furthermore, the combination of SAI and MCB may be able to reduce climate impacts better than either alone; the second goal is thus to assess this potential. Finally, this project will support integration of expertise between climate scientists and engineering, strengthening both disciplines. Given the risks of climate change, it is essential to understand to what extent different solar geoengineering approaches might contribute to an overall portfolio of response options. This project will introduce systematic design principles into Marine Cloud Brightening (MCB) research, and will carefully assess how SAI and MCB might complement each other. Existing MCB simulations have often simply introduced some specified perturbation and evaluated what happens, rather than starting with desired outcomes and determining both where to perturb, and how much forcing to apply in different regions, in order to achieve those outcomes. The broader MCB research community is now exploring how forcing in different regions affects the climate differently. This project will leverage this momentum, and build on the experience gained with SAI, by using optimization tools to systematically evaluate MCB as a design problem and develop multi-degree-of-freedom feedback algorithms to achieve desired climate outcomes in the presence of uncertainty. The approach thus introduces new tools that will be broadly useful for the research community going forward, and defines an approach for systematically evaluating the benefits and risks of MCB. Furthermore, this approach will enable a simultaneous optimization combining SAI and MCB to assess whether their combination could be “better” than either alone. Simulations will be conducted in climate models for different regions, and for combinations of regions. The final simulations conducted as part of this research will be made available to the climate impacts modeling community to better assess the role of MCB in managing future climate risks. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-02

Plant leaves perform vital photosynthetic functions, converting solar energy into sugars that empower all plant processes and directly impact crop yield. Leaves are multicellular organs that develop from meristematic, precursor stem cells, eventually forming complex, three-dimensional shapes that are critical for leaf function. Leaves of maize, a model plant for developmental research, comprise several grass-specific structures and features that maximize photosynthesis and provide structural support to the maize plant. This project will investigate the functional interactions of plant-specific genes with profound impacts on grass leaf development. The LIGULESS1 (LG1) gene functions to direct expression of other genes (i.e. transcription factors) that are involved in leaf width, length, and angle, with direct impacts on photosynthesis and leaf morphology. Three members of the WUSCHEL-related homeobox3 (WOX3) family of plant transcription factors are required to make leaves grow wide. Mutations in these wox3 genes give rise to short, mutant plants with leaves that fail to wrap-around and support the grass stems, which are thereby susceptible to lodging. Recent work has revealed that LG1 and WOX3 transcription factors interact during three-dimensional patterning of leaf angle and leaf wrapping. Genetic analyses of mosaic plants that have lost LG1 or WOX3 gene expression in specific plant regions during plant growth will reveal the timing, and cell/tissue/organ specificity of their respective functions. Candidate genes required for leaf-wrapping will be identified, and interactions between LG1 and WOX3 proteins will be analyzed in transgenic plants from a related grass, to better understand the mechanisms of grass leaf development. The PI will train undergraduate summer interns through a Research Experiences for Undergraduates (REU) program and provide training in state of the art molecular genetics research to a graduate student. The PI will teach a 3 credit science course for incarcerated students seeking an Associate Degree at a NY state penitentiary. A fundamental question in developmental biology is how growth and differentiation of lateral organs are coordinated along three-dimensions, comprising the dorsiventral, proximodistal, and mediolateral axes. Leaves arise from stem-cell pools called shoot apical meristems (SAMs) and are dorsiventrally-asymmetrical from their inception. Juxtaposition of dorsal and ventral domains organizes leaf-primordial outgrowth from the SAM along the mediolateral and proximodistal axes, creating a leaf that is tall, wide and flat. The maize leaf is an excellent model system for genetic, genomic, and cell-biological investigations of the mechanisms whereby axial development is spatially-regulated and coordinated. At maturity, the maize leaf is a strap-like structure with a distal, photosynthetic blade and a proximal sheath that wraps-around and supports the stem. Patterning of sheath wrapping is decidedly non-random in grasses. At the boundary between the blade and sheath, grass leaves develop a membranous outgrowth of epidermally-derived ligule, and a wedge-shaped auricle that function as a hinge to create leaf angle. Mutations in the grass transcription factor LIGULESS1 (LG1) remove the ligule and auricle, whereas mutations in WUSCHEL-related homeobox3 (WOX3) genes disrupt mediolateral leaf outgrowth and disrupt patterning of sheath margin wrapping. Higher-order wox3 and lg1 mutants reveal that LG1 and WOX3 transcription factors interact during proximo-distal and mediolateral patterning and leaf wrapping. Clonal sector analyses will reveal the ontogenetic timing, tissue-layer specificity, and cell-autonomy of LG1 and WOX3 function. State-of-the-art transcriptomics will identify candidate genes involved in sheath wrapping, and interactions of LG1 and WOX3 proteins will be examined in planta during ontogeny. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2025-01

PROJECT SUMMARY / ABSTRACT The priming of CD8+ T cells in the lymph node ultimately determines the success of the host response to intracellular pathogens. Priming determines whether the pathogen is cleared by effector T cells and immunity is established by memory cells. Despite the importance of this key step, our understanding of the events that occur in the lymph node early after infection is still considered a black box and is largely based on studies performed in adult animals. Indeed, there is almost no information available on how the lymph nodes change from birth to adulthood. As a result, we do not understand how T cells become activated in the lymph node at different stages of life, and the lack of such information has made it difficult to develop new strategies to enhance immunity in early life. Using new technology, we plan to construct the first molecular atlas of T cell development in lymph nodes and determine how the cellular interactions and communication networks change during CD8+ T cell priming throughout childhood. Our hypothesis is that CD8+ T cells made in early life are located in an ‘innate niche’ near the subcapsular macrophages and help to limit transnodal spread of pathogens during the primary response, whereas CD8+ T cells made in adulthood are found in an ‘adaptive niche’ near the central paracortex and are superior at providing systemic protection to secondary infections. In the first aim, we will determine how the spatial organization of T cells changes in the lymph node throughout childhood. In the second aim, we will examine how the lymph node shapes the CD8+ T cell response to infection in infants and adults. In the third aim, we will evaluate the impact of microbial exposure on the development and function of lymphoid CD8+ T cells. The obtained results are expected to provide the research community with a new paradigm for T cell activation and an invaluable resource for understanding how immune responsiveness changes at various stages of life. This new atlas of T cell development has broad implications for the design of more precise immunotherapies and the development of more effective vaccines.

NSF Awards · FY 2025 · 2025-01

The 8th Conference on Analysis, Probability, and Mathematical Physics on Fractals, to be held at Cornell University in June 2025, will bring together leading researchers and early-career mathematicians to foster collaboration, innovation, and education in this evolving field. Fractals, which play a critical role in modern mathematical research, serve as a bridge between pure and applied mathematics, with applications ranging from modeling random processes to understanding physical phenomena. The conference will provide a platform for advancing knowledge in these areas while promoting the education of the next generation of mathematicians. More information can be found at https://math.cornell.edu/cornell-conference-analysis-probability-and-mathematical-physics-fractals. This five-day conference consists of three structured components: plenary sessions, mini-courses, and parallel sessions. Plenary talks will feature recent breakthroughs by leading researchers in topics such as differential equations, random processes, and physical models on fractal spaces. Mini-courses will provide foundational knowledge and expose participants to significant open problems, engaging advanced undergraduates, graduate students, and early-career researchers. Parallel sessions will enable all attendees to present their work and exchange ideas. By building on foundational work in the field and fostering collaboration across disciplines, the conference aims to explore new research directions in potential theory, geometric analysis, and probabilistic approaches on non-smooth and fractal spaces. This event continues a 20-year tradition of advancing knowledge, cultivating young talent, and encouraging innovation in mathematical research on fractals. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-01

Cornell Tech, in collaboration with Hofstra University and the University of Illinois, seeks to expand its proven Break Through Tech AI Program designed to equip all undergraduate students with the skills needed to thrive in the fast-evolving fields of artificial intelligence (AI) and machine learning (ML). By expanding participation in high-quality AI education through a network of Instructional Hubs, this project aims to double the number of students served annually. This new generation of AI leaders will help ensure advances in responsible AI and promote US competitiveness in this exploding technical field. This project focuses on scaling up the ML Foundations component of the Break Through Tech AI program. This nine-week, skills-based training course is delivered by faculty and graduate students from newly established Instructional Hubs at various institutions. The expansion will involve recruiting five new Instructional Hubs, training instructors through a “Train the Trainer” program, and delivering synchronous lab sessions to ensure students gain practical, industry-relevant skills. By the end of the three-year grant period, the program aims to serve 1,500 students annually, significantly enhancing the readiness of the STEM workforce. This project will contribute to the field by providing a scalable model for AI/ML education and generating valuable data on the effectiveness of distributed instructional hubs in expanding participation in cutting-edge AI education. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-01

This award is funded by NSF Global Centers program, an innovative program that supports use-inspired research addressing global challenges through the bioeconomy. It is co-funded by the Office of International Science and Engineering, and the Directorate for Geosciences. It supports U.S.-based researchers developing global international partnerships and building multi-stakeholder engagement to advance use-inspired research, in the aim to develop their project toward a large-scale international effort. Building a carbon-neutral sustainable energy infrastructure is one of the most pressing challenges of our time. It requires an enormous supply of critical metals. Traditional metal extraction and separation form ores pose significant environmental risks, especially given the large supply needed. Biomining, a promising alternative, uses microorganisms to dissolve minerals, and separate and concentrate metals. It offers a more environmentally friendly approach. It is already a growing industry supplying 5% of the world’s gold and 15% of its copper. However, industrially useful microbes for extracting energy-critical metals from ores and waste materials are still undeveloped. The Microbe-Mineral Atlas project aims to address this gap by investigating how microbes interact with minerals and rocks. This is a crucial step toward using synthetic biology to create microorganisms capable of mining critical metals. The project also examines the necessary policy adaptations for this emerging technology. Furthermore, it provides comprehensive education and training to students at all levels, preparing a future workforce to responsibly commercialize these innovations. By fostering innovation and promoting environmental stewardship, the Microbe-Mineral Atlas project paved the road to the global transition to renewable energy. The project is driven by four key questions that guide its research activities: (1) How have microorganisms adapted to the mineral and metal diversity found in natural and man-made environments, and what unique adaptations can be leveraged? To answer this, the team uses bioprospecting, metagenomic sequencing, advanced microbe cultivation, and high-throughput screening to catalog organisms and genes involved in mineral interactions, and isolate new synthetic biology chassis organisms for biomining. (2) Can we harness the geobiodiversity discovered through genetic engineering for more efficient and sustainable metal extraction, separation, and concentration? The team uses advanced genetic engineering to develop engineered organisms with enhanced metal extraction, separation, and accumulation capabilities. (3) What are the benefits and complexities of new biotechnologies for mining and refining low-grade and recycled metals? This is assessed using life cycle analysis. (4) What social and regulatory frameworks are necessary for a sustainable future in mining? The project explores these frameworks through public opinion surveys and policy analysis. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2025-01

PROJECT SUMMARY In all domains of life, cells must employ tightly controlled mechanisms to regulate global processes in response to environmental inputs. In bacteria, signaling through the nucleotide second messenger 3’,5’-cyclic diguanylic acid (c-di-GMP) is one of the most conserved mechanisms cells use to trigger lifestyle changes in response to specific environmental cues. Although the enzymes that synthesize and degrade c-di-GMP can be found in all bacterial phyla, studies of this second messenger have focused on model species belonging to the Phylum Pseudomonadota. A key knowledge gap is understanding how this fundamental mechanism governs regulation of gene expression in diverse bacterial phyla. This project will address this by characterizing the molecular mechanisms and evolution of c-di-GMP signaling in the antibiotic-producing bacterial genus Streptomyces, which belongs to Phylum Actinobacteria (synonym Actinomycetota). In Streptomyces, c-di-GMP is the central integrator controlling a highly unusual life cycle that involves progression from vegetative growth to production of reproductive aerial hyphae that differentiate into chains of spores. To investigate the molecular basis and functional diversification of c-di-GMP signaling, this project will focus on three areas: (1) the mechanisms through which c-di-GMP regulates progression through the developmental life cycle in the model species Streptomyces venezuelae; (2) the evolution and distribution of conserved components of c-di-GMP signaling networks; and (3) the impact of c-di-GMP on antibiotic biosynthesis, which is tightly controlled along with the developmental life cycle, in diverse antibiotic-producing actinobacterial species. These studies will contribute to a fundamental understanding of how bacterial control gene expression and will leverage this knowledge to manipulate antibiotic production.

NIH Research Projects · FY 2026 · 2025-01

PROJECT SUMMARY With the advent of high-throughput sequencing, pathogen genetic data have become an increasingly important source of information in the study and surveillance of infectious diseases. However, current computational methods for genetic epidemiology do not adequately capture the complexities inherent in the genetic consequences of realistic disease dynamics. This limitation hinders our ability to fully exploit this rich data source. The core challenge involves incorporating epidemic, ecological, and evolutionary factors, along with their interactions, into the computational framework. My lab’s central aim for the next 5 years is to address this challenge by developing novel statistical and computational methods, drawing on our expertise in population genetics, applied mathematics, and computation. First, we will develop efficient coalescent-based phylodynamic methods to jointly infer genealogies and model parameters based on pathogen genetic data while incorporating realistic biological and epidemiological processes associated with latent and polyclonal infections. We will devise new algorithms and inference frameworks capable of handling the inherent complexities in these scenarios based on the seedbank coalescent and metapopulation coalescent theories, respectively. Beyond the applications in genetic epidemiology, the newly developed methods will also provide a fundamental understanding of populations undergoing dormancy and metapopulation dynamics. Second, we will develop scalable inference frameworks for phylodynamics using pathogen genealogies (representing evolutionary and epidemiological relationships among samples) as an input data structure. Our approach will include integrating tree encoding with deep learning techniques and ensemble learning strategies to handle large datasets and model complexities, enabling a more robust and comprehensive framework for genetic epidemiology. Third, we will create a comprehensive epi-eco-evolutionary simulator that will be integral to generating synthetic data that accurately reflect real-world scenarios, thereby facilitating the development and testing of new hypotheses, algorithms, and models. Importantly, this tool will directly address the currently understudied epi-eco-evolutionary coupling, offering insights into how the genetic evolution and transmission dynamics of pathogens are intertwined. Finally, we will apply the conceptual and methodological advances from our research to the existing whole- genome sequencing dataset of Mycobacterium tuberculosis, the causative agent of tuberculosis. In summary, my research program will provide a deeper mechanistic understanding of how epidemiological, ecological, and evolutionary processes and their interplay shape the genetic diversity and epidemic trajectories of pathogens. This information will lay the foundation for improving the management and control of infectious diseases, such as tuberculosis, which disproportionately affects socioeconomically underprivileged populations.

NSF Awards · FY 2025 · 2025-01

The Antarctic ice sheet contains the world’s largest amount of fresh water and has the potential to become the greatest contributor to future global sea level rise. The dominant mechanism by which Antarctica currently loses mass is ice discharge, where ice on the continent flows into the ocean. Ice shelves are floating extensions of land ice that surround 75% of the Antarctic Ice Sheet and restrain continental ice from reaching the ocean. Therefore, understanding the processes that cause ice shelves to break apart is key to reducing uncertainty in how much and how quickly sea level will rise. Observational evidence demonstrates that liquid water on ice shelves, typically from surface melting, can sometimes lead to their collapse. Seawater infiltration into porous ice shelf firn (perennially-persistent porous snow that has not yet compacted into ice) is another pathway for water to access ice shelves; however, the impacts of this process on ice shelf stability remain understudied across Antarctica. Constraining the impact of seawater infiltration on ice shelf stability requires a better understanding of the total extent of ice shelves affected, the internal structure of these water bodies, and the total volume of liquid water stored. The project will include participation from undergraduate student researchers from the Cornell GeoPaths Geoscience Learning Ecosystem (CorGGLE) and develop a hands-on radioglaciology workshop for early-career researchers. The project will characterize the extent and morphology of seawater/brine aquifers across Antarctic ice shelves by utilizing approximately 180,000 kilometers of existing airborne ice penetrating radar data. The researcher will (1) adapt previous semiautomatic meltwater firn aquifer detection algorithms to map the extent of brine aquifers across ice shelves where there is available radar data; (2) use radar attenuation and reflectivity models to estimate the liquid water volume of brine aquifers; (3) utilize satellite imagery, surface digital elevation models, and ice thickness datasets to determine where and how seawater infiltrates ice shelf firn; and (4) integrate radar data with ice shelf stratigraphy models to estimate the persistence of deep entrained brine layers and constrain their potential impacts on ice rheology. This project will clarify the relative importance of brine aquifers in the ice shelf system and their potential to impact ice shelf stability. It will also produce new datasets needed to constrain future ice shelf hydrology and hydrofracture models that will determine the full influence of these systems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2025 · 2025-01

NON-TECHNICAL SUMMARY This award, provides support for two summer-long workshops, entitled the Solid State and Materials Chemistry Collaboration Incubator (SSMC-CI), that merge the advantages of in-person hackathon-style events and longer-term residential programs to more effectively address materials science problems and nucleate new methods and techniques. The on-going and rapid evolution of artificial intelligence and large-scale computations can be witnessed in many areas of everyday life, from the way advertisements are tailored to individual users on the Internet to the generation of images and text from simple prompts. These advances also have the potential to transform the methods by which scientists design and discover new materials to meet the technical and environmental challenges the nation faces today and will meet in the future. The expertise needed to adopt data science and computational techniques, however, is quite distinct from that used by researchers skilled in the synthesis and analysis of new substances, which in turn are different from the skills needed to measure materials performance. SSMC-CI aims to lower the barrier for materials scientists and data scientists to collaborate. It brings together teams of scientists from a range of backgrounds to collaborate on pressing problems in the areas of solid-state compounds and materials. Each workshop begins with an initial 3-day in-person session to jump-start interactions among team members followed by a program structured around online meetings to sustain and nurture these collaborations, with the goal of creating multidisciplinary teams that have a track-record of progress on scientific questions that are challenging to pursue through traditional approaches. The award is supported through the Solid State and Materials Chemistry program and the Condensed Matter and Materials Theory program, both in NSF’s Division of Materials Research. TECHNICAL SUMMARY Many of the most pressing challenges in solid state and materials chemistry call for an integrated, multidisciplinary approach that combines expertise in materials synthesis, properties characterization, theoretical analysis, computational simulation, and data-science methods. The formation of collaborative teams to meet these challenges encounter the difficulty of bringing people with the right combination of skills together and developing sustained interactions among them. This project, which is supported through the Solid State and Materials Chemistry program and the Condensed Matter and Materials Theory program, both in NSF’s Division of Materials Research, establishes two Solid State and Materials Chemistry Collaboration Incubator (SSMC-CI) events as annual summer workshops to support and nurture the nucleation and growth of such teams, in a manner that merges the advantages of in-person hackathon-style events and longer-term residential programs. Each the SSMC-CI workshop follows a program of the form: (1) a call for proposals of research problems and applications to participate, from which teams are formed, (2) an in-person hackathon in which teams begin to work on their respective projects, as well as receive training in data-science methods, (3) a series of online sessions, during which teams report on their progress and plans for next steps, and (4) a virtual symposium for the teams to make final presentations of their results and lessons learned from their projects. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-12

This NSF-BSF project develops theoretical and algorithmic foundations for online learning and decision-making involving sequential data under unknown stochastic models. Along with theoretical investigation and algorithmic developments, this project has a significant application component on real-time monitoring and control of critical infrastructure networks. Specific applications include probabilistic forecasting of renewable energy and electricity prices, and detecting emerging behaviors such as those induced by faults or cyber-attacks in information infrastructure. This research contributes to foundational technologies critical to the nation’s power and information infrastructures and fosters international collaborations and industry partnerships. Undergraduate and graduate education activities broaden the impact of this project. The research focuses on developing holistic approaches to integrating representation learning with real-time inference and decision-making. The technical approaches are rooted in classical foundations of statistical inference, advancing some of the most powerful model-based ideas of innovation representation, sequential decision-making, and distributed filtering with modern data-driven generative AI solutions to overcome critical barriers arising from unknown, nonparametric, high-dimensional time series models. Research activities are structured under three thrusts: (i) developing a theoretical and algorithmic foundation for representation learning of nonlinear and nonparametric time series models, (ii) developing statistical inference and learning methodologies in both centralized and distributed settings for sequential data under unknown nonparametric stochastic models, and (iii) applying, validating, and evaluating developed solutions to critical infrastructure monitoring using field collected real-time data. Tightly integrated with the research activities are extensive collaborations with the leading power industry and cybersecurity industry, in particular, the IBM Cybersecurity Center through the NSF-BSF collaboration. This project also enriches undergraduate and graduate curriculum by developing experimental courses to provide hands-on research experiences to students. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Awards · FY 2024 · 2024-12

Whirligig beetles are aquatic insects that primarily live on the water surface. They display rapid but controlled movement and sensitive perception that enables seamless navigation on and below the water surface. These abilities support critical functions such as predator avoidance, prey capture, and multi-environment propulsion. The whirligigs represent a model for autonomous systems. To translate the whirligig’s movemente into robotics or related fields, the underlying fluid dynamics must first be understood. The findings of this proposal could lead to the development of miniature autonomous vehicles and robots functioning in multiple environments, with implications for search and rescue missions, precision agriculture, and national defense. Moreover, the integrated education and outreach plan aims to highlight the hidden beauty of water surface flows, revealed by whirligigs and other biological organisms, to undergraduate and K-12 classrooms. Through the development of affordable, student-safe, and environmentally friendly fluid dynamics tools, students will gain hands-on experience. This engagement will allow them to create and observe natural flow, anchoring fluid mechanics concepts to reality and inspiring future fluid dynamists. The primary research objectives are to experimentally investigate the fluid dynamics behind the whirligig beetle’s propulsion on the water surface and underwater, its diving (i.e., transitioning from water surface to underwater), and its food particle detection using surface ripples. Aim 1 will investigate the differences in the beetle’s propulsion between at the water surface and in deep water and sources of resistance to their diving, and how they overcome them. Aim 2 will study the fluid dynamics governing the beetle's use of water surface ripples to detect food particles on the water surface. The proposed project will provide insights into how surface tension and other hydrodynamic forces interact to achieve propulsion and communication/perception on water surfaces. Aim 3 will support education and outreach goals by designing and implementing accessible fluid dynamics experimental tools for undergraduate courses and K-12 outreach. Aim 4 will further extend the impact of these tools through dissemination at outreach events and professional conferences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2024-12

Project Summary The first step to initiate development of a new organism is to convert the terminally-differentiated mature oocyte to a totipotent cell capable of undertaking development upon fertilization. This change in cell state, called egg activation, includes the resumption of meiosis from its arrest in the mature oocyte and the translation of some stored maternal mRNAs and the degradation of others. Although these events are critical for fertility, what induces egg activation is not understood, except that a rise in oocyte calcium level is required. Since the transition initiates with no new transcription or translation, we hypothesized that post- translational switches mediate the transition from oocyte to activated egg by turning on or off the activity of proteins present in the egg. Consistent with this hypothesis, we found that the phospho-states of many proteins change during egg activation in Drosophila; this has since been seen in three other taxa. We hypothesize that calcium activates enzymes that regulate the phospho-state of critical proteins in the oocyte, allowing these proteins to then mediate critical egg activation events. We will test this hypothesis using Drosophila, whose large oocytes, excellent genetics, ‘omics tools, and high conservation of biomedically-relevant genes provide an optimal system for answering these questions. The first aim stems from our findings that a conserved mechanically-gated cation channel (TRPM) initiates a calcium rise in the oocyte and that the calcium-regulated phosphatase calcineurin, which is necessary for egg activation, is required for a significant fraction of the phosphoproteome changes. Molecules other than TRPM can then cause a slower, important, rise in calcium. We will determine their nature and contributions (Aim 1a). Because phosphorylation of some proteins increases upon egg activation, we will determine whether the calcium-regulated kinase CaMKII is also needed for egg activation in Drosophila, as it is in mouse (Aim 1b). In Aim 2, we will dissect the events downstream of those studied in Aim 1. By manipulating kinase activity using optogenetics, we will determine the effect on egg activation of altering the proteome’s phospho-state (Aim 2a). We will then focus on selected phospho-regulated proteins, particularly those involved in cell cycle control and translation initiation, testing whether the phospho-modifications that occur during egg activation alter their activity in ways that facilitate egg activation processes (Aim 2b). Given the conservation of egg activation, the mechanisms we define should reveal the basis of some pre- implantation-stage infertilities in humans (including identifying cases that would not be treatable with IVF) and for assessing the efficacy of IVF conditions. Our results will also help to understand the mechanisms by which calcium regulates myriad cell processes and their transitions.