California Institute Of Technology

NIH Research Projects · FY 2025 · 2024-09

PROPOSAL SUMMARY/ABSTRACT My long-term career goal is to broaden our understandings of molecular and cellular mechanisms governing hematopoietic cell fate decisions both in normal and pathogenic conditions as an independent investigator. A central question of my research is how broadly expressed transcription factors regulate a distinct set of genes in different developmental programs, as transcription factors’ ability to provide precisely required functional inputs in each cellular context is essential for life-long production of healthy blood cells. To address this, I propose to determine molecular mechanisms driving dynamic functions of Runx transcription factors in early thymic T cell development and megakaryocyte differentiation, two vastly different programs relying on Runx activities. Also, I aim to exploit a novel cell culture technique recapitulating the connection between bone marrow progenitor stages and early thymic progenitor stages. This will establish a new opportunity to define the roles of transcription factors in this developmental window, which was previously challenging due to lack of in vitro system. My preliminary studies suggest that Runx factors possess notable ability to switch their DNA binding sites in a context-specific fashion both within the same developmental trajectory at different stages as well as across different cell types. These dynamic Runx binding sites are closely associated with the genes that are sensitive to Runx functions. Importantly, redistribution of Runx factors occurs across large genomic domains and multiple peaks appear and disappear coordinately. Also, cell type-specific Runx binding sites harbor distinct sets of other transcription factor motifs, suggesting that a unique ensemble of collaborators may be present in each cellular context. Thus, I hypothesize that 3D chromatin reconfiguration responds to or causes context-specific Runx binding site choices, and these dynamic Runx functions are driven by distinct co-factors in each program. To address this, I will determine whether developmental changes of 3D chromatin structure require or instruct Runx functions during early T cell development (AIM 1, mentored phase). Also, I will define which functional collaborators physically interact with Runx factors in early T cell development and megakaryocyte development and test which co-factors are necessary to guide cell type-specific Runx DNA binding (AIM 2A). Additionally, I will define the impact of cell type-specific partners on Runx functions independently of chromatin state by experimentally introducing mismatched-co-factors to non-native developmental context (AIM 2B). Finally, I will establish a novel in vitro system recapitulating the developmental transition from bone marrow progenitor phases to early thymic progenitor stages. I will exploit this system to test whether the principles underlying dynamic Runx functions apply to the activities of another multilineage-expressed transcription factor, c-Myb. Together, the studies in this proposal will show how globally expressed transcription factors execute context- specific functions in different developmental pathways in normal hematopoiesis, and how malfunction of these principles can cause hematologic pathologies, such as leukemia. 1

NIH Research Projects · FY 2025 · 2024-09

Project Summary/Abstract The studies described in this proposal seek to develop strategies for the synthesis of strained rings and heterocycles for two purposes: 1) the first total syntheses of novel azetidine-containing metabolites, and 2) rapid access to bifunctional strained ring and heterocycle building blocks. Regarding the first purpose, total syntheses of azetidomonamide A, azetidopyridone, and diazetidomonapyridone do not exist and are sorely needed so their biological functions in quorum-sensing behavior can be evaluated. These metabolites affect biofilm formation and production of redox-active metabolites in P. aeruginosa, which is partially implicated in adverse outcomes for cystic fibrosis patients. Thus, total syntheses of these metabolites are highly needed and will have a broader impact on human health through expanding understanding of biofilm formation by P. aeruginosa, and potentially allowing for development of anti-virulence treatments for it in the long term. For the second purpose, strained rings and heterocycles are increasingly prevalent in pharmacological motifs; strategies to access modular components are needed to enable expedient diversification and access to new bioactive molecules. For the syntheses of azetidomonamide A and diazetidomonapyridone (K99), we envision the development of intramolecular cyclization reactions to establish key challenging frameworks in the molecules, such as Z-exocyclic azetine moieties, 4/6 bicyclic pyridones, and 4/7 bicyclic carbamates. These efforts will not only allow us to establish the total syntheses of these metabolites, but contribute more broadly to chemical synthetic efforts in the development of new reactions to access these strained heterocyclic motifs. In the R00 component, we propose the development of organometallic methods to achieve the syntheses of bifunctional strained ring and heterocycle chemical building blocks. In the first phase, we anticipate diverting organometallic intermediates to Favorskii-type reactivity to generate N-heterocycles that contain multiple handles for further functionalization; in the second, we propose tuning organometallic intermediates to Ramberg- Bäcklund reactivity to access substituted strained-ring derivatives. In doing so, we will broaden knowledge of current chemical reactivity as well as provide strategies to make molecular scaffolds relevant to multiple industries, including those pertaining to pharmaceuticals. Overall, the proposed research is significant because it provides creative strategies to 1) establish the first total syntheses of azetidomonamide A and diazetidomonapyridone, which will enable their biological study, and 2) develop new reactivity paradigms for accessing modular molecular scaffolds with pharmacological relevance. Performing the K99 research in Prof. Reisman’s group at Caltech aligns well with their current success in the efficient total synthesis of complex natural products; this experience in the synthesis of strained heterocycles will augment my prior training in organometallic chemistry to prepare me for a future R1 academic career in which I develop methods to access these types of motifs in broader contexts.

NIH Research Projects · FY 2025 · 2024-09

Summary When searching their environment for food, animals often switch from making random changes in direction to reflexively orient upstream when they smell an attractive odor, followed by rhythmic turns when they lose the plume. Random changes in direction are traditionally interpreted as manifestation of a stochastic search process. In this proposal, we test new hypothesis for the role of these random turns: animals turn deliberately to gather information before and after they change direction—allowing them to compute important internal and external state parameters such as wind direction, wind speed, ground speed, and altitude that they cannot directly measure. This idea is theoretically feasible based on the principle of observability, a powerful concept we borrow from control theory and informatics that is critical in the design of autonomous vehicles; here, we apply it to address fundamental questions in neuroscience. To do so, we exploit the natural behavior of flies, which execute rapid turns (called body saccades) as they search during flight. Our research program exploits state-of-the-art experimental techniques pioneered in the labs of team members, which we will leverage with genetic techniques and the rapidly emerging connectome databases available to the fly community—an integrated approach that has already provided our team with a solid foundation for our proposed effort. From wind tunnel experiments we have discovered that hungry flies execute a brief, stereotyped turn when they first experience an odor stimulus, which we postulate they use to estimate ambient wind direction and speed before either executing an upwind surge, or initiating a circling behavior in still air. From physiology experiments, we discovered a small network of identified cells that serve as command neurons for generating spontaneous saccades (DNa0X and DNb01) and another, specialized neuron that regulates their execution during flight (VS041). These preliminary results provide a strategic entry point for our proposed work, which is separated into four Specific Aims: (1) Test whether DNa0X and DNb01 are responsible for saccades that mediate olfactory search. (2) Identify upstream regulators of the saccade generating circuits responsible for the olfactory search behavior. (3) Determine the role of spontaneous saccades in gathering information. (4) Develop circuit-inspired, agent-based predictive models of olfactory search This effort to elucidate the circuitry that controls both stimulus-evoked and spontaneous turns during olfactory search and test their potential role in information-gathering links the ethologically important behavior of olfactory search across spatial and temporal scales—from the transient responses of individual neurons to the long flight trajectories of whole animals as they search for food. While not widely used in systems neuroscience, we believe that the concept of observability will provide a major conceptual advance in understanding how brains function; specifically, how the nervous system can collect information at different points in time and space and use it to compute parameters that are for critical subsequent behavioral actions.

NSF Awards · FY 2024 · 2024-09

Aging is characterized by the progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This vulnerability is further compounded by the loss of resilience and stress resistance. Despite the development of various biomarkers and tests, such as the pan-mammalian epigenetic clock, the inflammatory aging clock (iAge), and the timed walking test, these tools are often limited in scope, labor-intensive, and reliant on specialized laboratories. There is a pressing need for a diagnostic tool that can integrate multiple biomarker types, offering continuous, real-life assessments of aging in a more accessible and convenient manner. Sweat, an easily collectable body fluid from the skin surface, contains rich physiological and molecular information. This project aims to leverage the emerging potential of personalized healthcare to revolutionize traditional medical practices through the development of a wearable sweat-sensing platform capable of non-invasive, continuous, and laboratory-independent assessment of biological age and resilience. The AGE RESIST project brings together an interdisciplinary consortium of renowned researchers from leading academic institutions to achieve the following objectives. (1) Exploration of Novel Biomarkers: Identify and explore novel sweat-based molecular biomarkers associated with heat strain and aging, to construct a comprehensive age clock of resilience using advanced machine learning algorithms. (2) Validation of Biomarkers: Prospectively validate the identified biomarkers through clinical studies to ensure their reliability and accuracy. (3) Wearable Platform Development: Integrate the validated biomarkers into a state-of-the-art wearable sweat-analyzing platform that enables real-time, non-invasive monitoring of biological age and resilience. This collaborative U.S.-Swiss project is supported by the U.S. National Science Foundation (NSF) and the Swiss National Science Foundation (SNSF), where NSF funds the U.S. investigator and SNSF funds the partners in Switzerland. 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 · 2024-09

The fate of many stars, such as our Sun, is to collapse to a small, but very hot, White Dwarf (WD) star. These WDs cease fusing light elements into heavy elements and slowly cool. Astronomers find a large abundance of heavy metals, like iron, in the atmospheres of many WDs. Theoretically, these elements should sink quickly in white dwarf atmospheres and disappear. This suggests that rocky material must fall onto the white dwarf surfaces continuously. Current understanding of this problem invokes the breakup of ancient asteroids, due to the gravity of large planets. This idea, however, is increasingly at odds with observations. The investigator proposes a new solution, that heavy elements come from collisions with the dusty outflows of dying stars. The study will explore how these planetesimals form, how their orbits change, and how they pollute white dwarfs. The research will give new insights into the final stages of planetary systems and the life cycles of stars. It will also support education and diversity through outreach programs with high school students and teachers. The project will be carried out in three main tasks. First, it will investigate how second-generation planetesimals form in the dusty outflows of asymptotic giant branch stars. Second, it will analyze the orbits of these planetesimal halos to see how much material stays bound to the white dwarfs versus how much is ejected into space. Third, it will model the process of white dwarf pollution through long-term simulations to understand how material moves to white dwarf surfaces and the dynamics within the planetesimal halos. By challenging current theories and proposing a new idea, this project aims to solve gaps in existing models of white dwarf pollution, using advanced computational tools to give new insights into the evolution of stars and planetary 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 2024 · 2024-09

While the discovery of exoplanets was one of humanity's longest-awaited scientific achievements, there remain outstanding goals: (1) the advancement of our knowledge of the formation and evolution of planetary systems, and (2) the discovery and characterization of habitable planets. This technology program directly addresses these important goals by providing new astronomical instrumentation lay the groundwork for the detection of Earth-like planets. A key missing technology is a wavelength calibration light source in the blue-visible region of the spectrum. This project will provide this technology by designing a new mechanism to produce a visible and near-ultraviolet calibration system called a laser frequency comb. The investigators will evaluate the reliability of this calibration system over extended timescales, which will be critical to the improved robustness, cost and efficiency. This system will be used with the Keck Planet Finder instrument. Exciting updates from this work will be used for public outreach, education and inclusivity activities. A laser frequency comb (LFC) has intrinsic properties that make it an ideal calibration source for radial velocity spectroscopy with precision better than 10 cm/s. The full potential of the LFC has not been realized for astronomical applications because of its limited spectral extent into the visible and near ultraviolet, generally poor reliability that requires regular maintenance, and high cost. This research will address these challenges by developing a new nonlinear nanophotonic waveguide technology based on poled thin-film lithium niobate. The lithium niobate platform provides the advantage of chi-squared nonlinear interactions in domain-engineered waveguides that enable the generation of light in the critical 350-500 nm spectral band with 10-100 times the efficiency over existing silica fibers. Indeed, starting with a narrowband comb at 1550 nm, the full wavelength coverage will extend from 350 nm to beyond 2000 nm. In addition to the long-term goal of detecting Earth-analogs, LFC-quality calibration in the blue (<500 nm) will help deliver the masses of Earth-size planets from Kepler (whose radii are known), yielding valuable bulk density measurements, expand our ability to understand internal structures of cool stars via precision Doppler asteroseismic measurements, and help shed light on the enigmatic population of super-Earths and sub-Neptune-size planets that require precise masses to constrain compositions. Moreover, this cross-disciplinary work will provide training the next generation of instrumentation scientists and engineers. 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 · 2024-09

All chemical elements are present dissolved in the ocean. Differences in their concentrations and in the relative amounts of their isotopes at various locations and depths are used to understand the workings of the ocean and the geochemical cycles of the planet as a whole. In this project, investigators from three institutions will conduct the first study of the marine chemistry of zirconium isotopes. Pilot data from the team have indicated differences in isotopic composition between seawater and sediments. The proposed work will build on these pilot data by characterizing the zirconium isotopic composition of a comprehensive array of seawater, particle, and sediment samples already collected from the Pacific Ocean. One aim of the work will be to test the idea of whether zirconium isotopes in sediments provide a record of past ocean conditions. The project will support one PhD student and provide research experience for one undergraduate student. The results of this research will be incorporated into class material taught by the PIs and reported in plain language summaries on their research websites and through university press releases. This work will support a diverse, interdisciplinary team of three early career faculty. The team will promote broadening participation in science through targeted educational outreach including the development of educational modules for high school students to spur interest in chemical oceanography and isotope geochemistry among students at an early career stage. Previous work on high field strength elements including zirconium (Zr) and hafnium (Hf) indicated that the ratio of dissolved Zr/Hf varies extensively and systematically with latitude and depth in the ocean. Pilot data obtained by this team on the stable Zr isotopic composition of marine authigenic sediments and seawater has revealed systematic fractionations, but further investigation of this proxy in seawater profiles and marine particulates that intersect major currents is crucial for: i) providing insight into the mechanisms responsible for the isotopic fractionations observed in the ocean; and ii) further developing their application as a potential tracer of paleo-oceanographic processes. The proposed work aims to build upon the pilot observations by characterizing the Zr isotopic composition of seawater, marine particulates, sediments, and leaches in an array of well-characterized samples collected during a previous cruise. This project will apply high-precision, novel non-traditional stable isotope techniques to marine samples to: (1) determine the stable Zr isotopic composition of various endmembers in the ocean (dissolved, particulate, authigenic sediments), (2) probe whether these isotopic compositions correlate with water mass age, (3) test whether the Zr isotopic composition of authigenic sediments faithfully record the water composition they originated from, and (4) test whether adsorption of dissolved Zr onto sinking particulates is the driver of the observed Zr isotopic fractionation in the ocean. 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 · 2024-09

The underlying geophysical connections linking great earthquakes with plate tectonics will be addressed using sophisticated models. These seismic events are the largest earthquakes with magnitudes of nine or higher and are among largest sources of natural hazard affecting many countries, including the United States. Scientists have long known that these earthquakes are linked to plate tectonics and occur where an oceanic plate dives into the earth’s interior at a subduction zone, like the one along the coasts of Washington State, Oregon and northern California. Unfortunately, fundamental issues remain as to the reasons where and when they occur. This interdisciplinary team will link the long-term physics driving and resisting plate tectonics with that of great earthquakes. The outcome of the models will be a deeper understanding of earthquake occurrence. Currently, the ability to solve the set of equations describing the physics of this coupled problem is beyond the ability of mathematical methods. Consequently, this project brings together mathematical scientists with earth scientists to attempt to solve this problem collaboratively. Mathematically, problems like this are solved on the largest supercomputers and are described by many equations. For the plate tectonics problem by itself, the equations change only a small amount from one moment of time to the next in the computer model, but in this coupled problem only a set of the equations change when an earthquake happens and so the mathematicians will discover and implement new ways to solve such large sets of equations. Meanwhile, the earth scientists will use the new methods to understand the basic physics of the coupled earthquake and plate tectonics problem, ultimately tailoring the methods to models of individual plates and faults, such as the Juan de Fuca Plate which subducts below the Pacific northwest. The algorithms are expected to efficiently use the largest supercomputers now in the planning stage, including the NSF-planned LCCF (Leadership-Class Computing Facility). Moreover, the computer software, called Rhea, will be distributed open-source and will be well-engineered and documented. The team will collaborate with the Computational Infrastructure for Geodynamics, supported by the NSF, for the distribution of Rhea to the broader scientific community. The PIs will train graduate students at Caltech, Virginia Tech, and NYU at the boundary between the mathematical sciences and science applications. The team will participate in outreach programs: In California through a program that brings geophysical science to local Title I schools; in Virginia, through one that provides outreach projects for local high schools; and in New York City, through a program that focuses on exposing undergraduates to mathematical research. The forces controlling plate tectonics and the conditions leading to great earthquakes are currently treated as separate, fundamental problems, but in this project, they will be linked with a focused effort to develop and apply a new generation of finite element methods with solver adaptivity that will scale on the largest computers. The activity will involve major advances in mathematical and computational algorithms for multi-physics problems, the team will bridge the space–time divide and self-consistently compute the long-term motions of tectonic plates and the intervening space–time evolution of stress within and adjacent to plate boundaries. This undertaking is beyond currently available methods and mathematically requires new concepts to allow tracking the shifting—but localized—regions of enormous computational need during earthquakes. The team will expand the notion of space and time discretization adaptivity towards solver adaptivity. Solver adaptivity will use equation residuals to focus computing resources towards the most efficient solution of large linear and nonlinear systems of equations. Since the system arising by discretizing the equations in the earthquake–plate tectonic problem typically has tens and hundreds of millions of unknowns, solvers based on matrix factorization are out of question and one must rely on iterative solvers that also allow parallelization. The algorithms are expected to scale on the largest anticipated supercomputers with distributed memory and computational elements, such as the NSF-planned LCCF (Leadership-Class Computing Facility). As such, the scalable algorithms will fill an important need and demonstrate the efficient use of future LCCF machines. The methods will be incorporated into the highly scalable Stokes solver, finite element package Rhea. Visco-elasticity and frictional material models will be implemented into Rhea. The science and mathematical challenges will be addressed with an interdisciplinary team consisting of a geophysicist who works on the dynamics of plate tectonics, a mechanician who works on the physics of earthquakes, and applied mathematicians who work on linear and nonlinear scalable PDE solvers. The team will apply the methods to understand the coupled physics generically, first in two dimensions and then in three dimensions. Then, using models regionally tailored by the explicit incorporation of seismic, geologic and fault structure, they will simulate Cascadia and the northwestern Pacific subduction systems. This project is jointly supported by the Computational and Data-Enabled Science and Engineering in mathematical and Statistical Sciences program in the Division of Mathematical Sciences and the Geophysics program in the Division of Earth Sciences. 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 · 2024-09

Gravitational-wave astronomy has now opened a new window to the universe, which along with conventional telescopes, significantly broadens our understanding of astrophysics and cosmology. Cosmic Explorer is a concept for a next-generation gravitational-wave observatory in the United States, enabling the detection of nearly every black-hole collision in the observable universe. To achieve the unprecedented sensitivity of this observatory, significant R&D effort needs to be invested in designs that will minimize various sources of noise. This award addresses a major noise source, namely stray light, and will produce a conceptual design for its mitigation. Specifically, this award enables a team of scientists and engineers to analyze how stray light in the interferometer’s 40km arm cavities may limit Cosmic Explorer's sensitivity and produce an initial conceptual design for the beamtube baffles. Mitigating stray light in the beamtubes is a high-priority research topic, as it directly impacts the facility design and cost. In addition, the project will produce requirements for surface roughness of the mirrors used as test masses in the interferometer and explore low-scatter vacuum-compatible materials. This award is one of a series of NSF awards that together will produce conceptual designs and technologies to enable the realization of Cosmic Explorer. 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 2024 · 2024-09

PROJECT SUMMARY Sleep disorders are pervasive and cost approximately $100 billion a year, yet the mechanisms that regulate sleep are still poorly understood. Previous sleep research has focused on neurons and some neuronal factors that regulate the homeostatic process of sleep. However, an understanding of how astrocytes, a type of glial cell, contribute to the sleep homeostat is less well understood. We propose a series of experiments to investigate the role of astrocytes in regulating homeostatic sleep need which exploit key features of larval zebrafish. The advantages of using larval zebrafish for this purpose is their amenability to whole-brain calcium imaging, with single cell resolution, which is possible due to their transparency and relatively small but conserved vertebrate brain, as well as their amenability to large-scale behavioral assays. Using larval zebrafish and our custom-built two-photon selective plane illumination microscope (2P-SPIM), we will perform several imaging and perturbation experiments that record whole-brain astrocyte activity in both natural and induced sleep and wake states. We then will apply computational tools to segment individual astrocytes and identify astrocytes that may encode the sleep homeostat. In addition, we will use optogenetic, chemogenetic, and loss-of-function perturbation approaches to test for functional roles of astrocytes in sleep. This diversity supplement application describes an experimental and conceptual career development plan for a graduate student whose experimental goals are to (1) test the hypothesis that astrocytes encode homeostatic sleep need in zebrafish, (2) test the hypothesis that stimulation of astrocytes results in increased sleep, and (3) test the hypothesis that inhibition or loss of astrocytes results in decreased sleep. We also describe a detailed career development plan that addresses key gaps in the graduate student’s training. This diversity supplement application directly relates to the parent grant that proposes to explore neuronal mechanisms that underlie zebrafish sleep by extending these studies to astrocytes. Thus, the experiments described in the diversity supplement application are separate from, yet synergize with, those described for neuronal mechanisms in the parent grant. Together, the parent grant and diversity supplement have the potential to transform our understanding of mechanisms that regulate sleep homeostasis, which is important as sleep disorders impose physical and economic burdens on society.

NSF Awards · FY 2024 · 2024-09

The Epoch of Reionization (EoR) begins when the first luminous objects in the Universe form and their intense ultraviolet emission starts to reionize the neutral hydrogen of the intergalactic medium (IGM). With continued emission of ionizing radiation, reionization fronts form gradually expanding bubbles around the luminous sources. The growth of these ionized bubbles is patchy in both time and space, but the bubbles eventually merge and the EoR ends. Astronomers have yet to study the EoR through the most direct method: tracing the neutral IGM itself through detection of the redshifted 21 cm line. The CO Mapping Array Project is a Line Intensity Mapping experiment using a spectral line other than 21 cm. A collaborative project between California Institute of Technology, University of Miami, and University of Maryland will duplicate the existing Pathfinder receiver and use it to perform a survey of rhe carbon monoxide (CO) line across the sky. The research team will work with the Caltech Education Office to develop material to teach students in underserved high schools about coding and astronomy. During the summer, the project will provide training to teachers to deliver this material and will support the teachers with classroom visits during the school year. The field of 21 cm cosmology has the potential to probe the structure and evolution of the inter- galactic medium, from the Cosmic Dark Ages through to Cosmic Dawn, the Epoch of Reionization and beyond. There are many challenges to this work: a foreground-to-signal ratio spanning five orders of magnitude, strong radio frequency interference (RFI), and subtle instrumental systematic errors. The COMAP project expects to overcome these challenges. After the COMAP survey, the team will cross correlate the resulting CO temperature cube with observations of the same field by a 21 cm cosmology experiment, the Low Frequency Array. These experiments have very different systematic errors, RFI environments and foreground levels, and the planned cross-correlation will therefore be insensitive to these effects. The investigators forecast that the resulting constraint on the CO × HI power spectrum will be 30 times better than the best current limits on either CO or HI. This provides a path to the first unambiguous confirmation of the EoR-era 21 cm signal and a route to tighter constraints on the HI autocorrelation power spectrum alone. 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 2025 · 2024-09

Summary: Gene regulation is controlled by the dynamic localization of numerous regulatory factors to precise nuclear targets. Classic diffusion and affinity models alone cannot explain various aspects of how these processes occur, and growing observations suggest that regulation of gene expression is not a linear process that simply reflect the number of regulators and targets in a cell. Recently, spatial organization of regulatory molecules via formation of biomolecular condensates (BMCs) has emerged as a likely explanation for the non-linear regulation of gene expression. However, the functional roles of most condensates remain largely unknown because we lack methods to simultaneously measure the many different protein and RNA regulators that bind DNA, their 3D structural interactions in the nucleus, and gene expression within the same individual cell. To overcome this challenge, we will develop an integrative new framework consisting of cutting edge molecular and spatial measurements of DNA, RNA, and proteins within single cells combined with a novel machine learning approach to identify the critical molecular components required for organization of large, interconnected molecular interaction networks within BMCs. We will apply these approaches to dissect a long-standing question in neuroscience – how olfactory neurons stochastically express one, and only one, olfactory receptor gene out of the >1000 distinct gene located throughout the genome. The transition from polygenic to monogenic expression coincides with genomic transformations that organize the regulatory landscape of receptor transcription into competing multi-chromosomal enhancer hubs, localization of numerous regulatory proteins to distinct hubs, and a critical role for nascent receptor mRNA concentration in symmetry breaking between distinct hubs. The overall objective of this work is to develop generalized frameworks for measuring BMCs and for understanding and predicting relationships and causal components within them, as well as a detailed characterization of a foundational neuroscience model. We will accomplish this via the following Specific Aims: (1) Define the spatial and molecular composition and dynamics of BMCs within olfactory neurons, (2) Formulate a neural network model to identify critical nodes for BMC organization and function, (3) Validate the functional role of predicted causal “nodes” in olfactory receptor regulation. Our research team, with collective expertise in molecular mapping, computational biology, and olfactory system research, is uniquely positioned to address these questions.

NIH Research Projects · FY 2025 · 2024-09

ABSTRACT. Our PCA research center brings together the UCLA Neurosurgery team with the Caltech spatial single cell team to construct a comparative spatial atlas of low-grade gliomas. The collaboration between the three components of the PCA research center has already generated preliminary data in several glioma samples. We will expand this effort to generate a comparative atlas of gliomas with distinct progression outcomes using integrated spatial transcriptomics, proteomics, and chromosome profiling. By comparing the low-grade gliomas that eventually transform with ones that stay indolent or do not recur, and with IDH-mutant high-grade gliomas, we aim to understand the molecular and cellular mechanisms at the low-grade stage that are predictive of malignant transformation (MT) and to suggest intervention strategies to prevent MT. The comparative analysis will examine three types of changes in low-grade gliomas with different outcomes: cell type composition, tumor microenvironment, and pathway specific gene expression. From UCLA’s Brain Tumor Translation Resource (BTTR) center, we have already collected 99 fresh-frozen low-grade glioma samples and will collect approximately an additional 100 samples of low-grade glioma with different outcomes (MT, indolent, and no-recurrence). We will then generate an integrated multi-modal spatial atlas targeting 2500 mRNAs, 10 proteins and 10 DNA CNVs and translocations. From the high sensitivity and multiplexed RNA seqFISH assays, we will be able to capture not only cell type and microenvironment information, but also genes and pathways that could be causal for progression to malignancy. Lastly, we will use the data to 1) predict tumor progression based on the cell type compositions and microenvironments; 2) design intervention strategies based on the spatial data, using counterfactual inference models to affect immune infiltrating and other predictors of progression; and 3) build a model of tumor progression dynamics based on gene expression and mechanics of the tissue. Our comprehensive low-grade glioma tissue collection, the integrated spatial dataset with transcriptomics, proteomics and chromosomal abnormalities, and the models built using advanced machine-learning tools will extend the existing capabilities of the HTAN consortium and be interoperable. The atlas and the computational tools will be used by us and the wider scientific community to further understand the mechanisms leading to malignant transformation.

NSF Awards · FY 2024 · 2024-09

This award enables continuation of an experimental exploration of eruptive plasma behavior in a laboratory under conditions similar to those on the sun and in other astrophysical objects. While laboratory plasmas have a much shorter lifetime than the solar and astrophysical plasmas, namely microseconds compared to anywhere from hours to millions of years for astrophysical plasmas, they can model many of the same phenomena in a reproducible and controllable fashion allowing for detailed studies. The present effort will focus on the study of the observed X-ray generation in a magnetized relatively cold plasma, under conditions when such high energy emission is not generally expected. This study has relevance to solar flares which similarly produce X-rays and very energetic particles that can damage spacecraft, and, in extreme cases, are associated with electric power grids disruptions. The project will also continue to engage a local high school with a vast majority of students from under-represented minority groups, motivating interest in science and encouraging them to pursue careers in plasma physics or other science and engineering fields. The ongoing research program is focused on determining how a seemingly benign, cold, collisional plasma can suddenly erupt and generate a burst of energetic particles, extreme ultra-violet radiation, hard X-rays, and high-frequency waves. In doing so, it contributes to the goals of NSF's "Windows on the Universe: The Era of Multi-Messenger Astrophysics" program. The knowledge and understanding being gained apply to many astrophysical and laboratory plasmas, such as solar flares, astrophysical gamma ray bursts, X-ray bursts from terrestrial lightning, and dense plasma foci devices. The program employs a well-diagnosed laboratory device in which reproducible arched magnetized plasma structures in the shape of coronal loops are formed and then exhibit kink and Rayleigh-Taylor magnetohydrodynamic (MHD) instabilities. A sequence of these instabilities pushes the plasma to a regime where the MHD approximation fails and non-MHD phenomena develop. This failure occurs when the electron velocity distribution becomes sufficiently non-thermal, with a significant population of highly energetic electrons leading to the generation of X-ray bursts. The continued investigation of these phenomena will employ high-speed visible and X-ray movie cameras, polarimetry to measure magnetic fields, and direct detection of energetic electrons. 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 · 2024-09

This project seeks to address how supermassive black holes (SMBH) form in the early universe and how they create relativistic jets. The investigators will study two families of SMBHs that are very rare to determine the number of binary SMBHs. They will determine whether the recently discovered gravitational wave background is due to these objects. One early result from the James Webb Space Telescope is that there are far more binary supermassive black holes in the early universe than expected. The existence of so many binary supermassive black holes poses challenges to cosmology. The PIs will use the 40 m telescope at the Owens Valley Radio Observatory and the Very Long Baseline Array to study the structure of these objects. The PIs will combine the radio results with optical, infrared, X-ray, Gamma-ray, and gravitational wave observations. The work will be carried out by five graduate students, so this will be important of their career development. In addition, the PIs have started an outreach program, in which they will be studying the jets in these objects, with schools that work with students from disadvantaged backgrounds. The radio jets from SMBHs will be studied in great detail through their varying radio brightness and structure on the scale of light years. One rare class the PIs will study is SMBH Binaries (SMBHBs). About 1 in 100 radio jets is a SMBHB. The PIs have detected two convincing SMBHB candidates through their light curves. Their focused search should at least double the number of strong candidates. Each strong candidate is of great importance to multi-messenger astrophysics, since the SMBHBs produce gravitational waves that will in future be detectable by pulsar timing arrays. They will also study high-luminosity compact symmetric objects (CSOs). The brightest CSOs die out after ~5000 years, whereas most radio jets last up to tens of millions of years, suggesting that a different fueling mechanism drives the brightest CSOs. Astronomers think this is the capture of single stars by the SMBH in a tidal disruption event (TDE). The PI's will test whether these powerful CSOs really do die out at ~5000 years. By studying these two rare classes, each of which probes details of the central engines in a unique way, they will gain crucial insights into the jet formation and launching mechanism as well as into the SMBHs themselves. Most importantly - if the initial results on CSOs are confirmed in this study, then the smallest CSOs will evolve on timescales of a few years. This will make possible the direct testing of the general relativistic magnetohydrodynamic theory and simulations of relativistic jets. 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 · 2024-09

Time-domain astronomy is one of the four science pillars of Vera C. Rubin Observatory, which is co-funded by the NSF and set to start survey operations in 2025. Over the past six years, the Zwicky Transient Facility (ZTF), a mid-scale observatory led by California Institute of Technology and largely funded by the NSF, has served as the training ground for the time-domain community across a breadth of astrophysics. This research program will provide at least one year of joint ZTF+Rubin operations to facilitate synergistic science, multiplying the science return of what either survey can do independently. The data produced from nightly joint operations will yield important science results, along with the necessary training to apply transfer learning using advanced machine learning algorithms. The broader societal impact program focuses on mentoring: graduate students for PhDs, postdoctoral scholars, undergraduate students for summer projects and senior theses, and high school students and high school teachers for summer projects. The public outreach plan includes a Pokemon-style mobile app called ZARTH, the Palomar Observatory visitor center, public lectures and timely media articles reporting the newest discoveries. This research award is partially funded by a generous gift from Charles Simonyi to the NSF Astronomy division. The project includes significant contributions to Vera C. Rubin Observatory’s Legacy Survey of Space and Time. This project is also relevant to Windows on the Universe: Multi-Messenger Astrophysics. The intellectual merit of joint ZTF+Rubin operations spans all facets of time-domain astronomy. ZTF will observe the accessible Rubin footprint (11K sq deg) twice a night every night. Every month, for two nights, ZTF will do a continuous cadence exercise on the Rubin deep drilling fields. Joint ZTF+Rubin operations for at least one year will yield over 1500 spectroscopically classified supernovae detected by both surveys that can squarely address the power source, mass-loss history and luminosity function questions. The majority of these supernovae will be Type Ia and joint detections will yield the necessary calibration with the precision needed for cosmology. Large samples of rare classes of transients such as tidal disruption flares will be uncovered. Compact white dwarf binaries will be found in the Rubin footprint, which can be thoroughly characterized in preparation for the LISA gravitational wave mission. Joint ZTF+Rubin data may even enable serendipitous discovery of a few kilonovae even while the gravitational wave interferometers are offline. Overall, concurrent ZTF operations will amplify early science with Rubin in the very first year of operations and lay the transfer learning groundwork to maximize the time-domain science for the rest of the decade. 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 · 2024-09

Starting with the Nobel-Prize winning detection of a “hot Jupiter” in 1995, the Doppler technique based on stellar spectra has been a ground-breaking method for finding planets around stars other than the Sun. This and other techniques have indicated that most stars have planets with masses of just a few Earth masses – small enough to have rocky surfaces – with orbital periods of ~1-300 days. Direct imaging space missions may one day record the light of these planets, but techniques to measure such small masses still need maturation. In this project, researchers in the California Planet Search collaboration will survey nearby stars for these low-mass planets, with the Keck Planet Finder (KPF) spectrometer at Keck Observatory. These data will almost surely detect new planets, and they will also allow researchers to learn how to reach Doppler precisions of 10 centimeters-per-second using the spectral features, which is necessary to detect Earth analogues. The project will support student researchers, as well as run an Introduction to Astronomy Research program for less privileged students, allowing greater access to the research skills students need for astronomy or other STEM fields. KPF is a high-resolution, fiber-fed spectrometer on the Keck I telescope, with high thermomechanical and optical stability for precise radial velocity measurements. Its advanced technology includes a laser frequency comb for calibration, exotic materials to reduce thermal sensitivity, and a separate UV spectrometer for stellar activity tracking. Early results demonstrate KPF's high throughput, efficient operation, and impressive Doppler stability, achieving the precision needed for this survey of ten nearby G and K-type stars. Each star will be observed approximately 100 times over three years with KPF, with an expected limiting detection amplitude on month-timescale orbital periods of 50 centimeters per second. To achieve this goal, the team will develop new algorithms to analyze the stellar spectra in a line-by-line approach. Discoveries of new systems of small planets will teach us about the formation and evolution of planets like our own and will be the best targets nearly all future studies of nearby stars. The survey spectra will have SNR = 600-1600 per reduced pixel, a new regime of precision. 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 · 2024-08

According to the National Academies’ 2020 Decadal Survey on Astronomy and Astrophysics "Gravitational wave astrophysics is one of the most exciting frontiers in science” and a next-generation gravitational-wave observatory in the US is “central to achieving the science vision laid out in the survey’s road map”. Current generation gravitational-wave detectors NSF's Advanced LIGO and Advanced Virgo have opened the era of gravitational wave astrophysics with the first gravitational wave detections from mergers of binary black hole, binary neutron star, and black hole-neutron star systems, and have triggered a broad range of studies including novel tests of General Relativity, understanding constraints on the interior of neutron stars, and new measurements of the Hubble constant describing the expansion of the universe. Cosmic Explorer, the next-generation ground-based gravitational wave observatory in the US, will transform and accelerate the field of gravitational wave astrophysics, enabling investigations of the farthest reaches of our universe and opening new collaboration pathways. This work will help ensure Cosmic Explorer reaches design sensitivity at the lowest frequencies by reducing the impact of disturbances in the local gravitational field around the detectors. This low-frequency sensitivity improvement will enable Cosmic Explorer to observe interesting heavy astrophysical objects such as intermediate-mass black holes and increase early warning capabilities that enable electromagnetic telescopes to view the moment of mergers of compact binary objects. The award will also train students and postdocs in STEM areas. Gravitational wave detectors are responsive to the gravitational forces, as described by Newton’s Law of Universal Gravitation, induced by any mass that is in close proximity to the instrument. Fluctuations in mass density due to propagating seismic waves create a limit to the instrument’s sensitivity. This work will develop techniques for assessing local gravity disturbances based on simulations and analysis of future measurements of the environment at proposed locations of Cosmic Explorer observatories and will help determine the viability of these candidate locations. The team will develop techniques for measuring and mitigating Newtonian noise using a series of simulations of seismic and other vibrational noise. This work will feed into the conceptual design of the Cosmic Explorer facilities and the local topology surrounding them to minimize the local gravity disturbances near the detector. It will also provide designs of instrument arrays necessary for measuring and inferring Newtonian noise that will be capable of mitigating the influence of those disturbances on the gravitational-wave data stream, and provide preliminary cost estimates for Newtonian noise mitigation. These efforts will enable the 20 dB of seismic Rayleigh wave mitigation required to meet Cosmic Explorer’s low-frequency sensitivity target. 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 · 2024-08

PROJECT SUMMARY Voice and upper airway (VUA) disorders affect nearly 30% of the general population and 80% of occupational voice users in the United States. Patients experience symptoms of vocal fatigue, hoarse voice, chronic cough or breathing difficulties, affecting their daily communication and swallowing functions. Many of these symptoms can be modified behaviorally and with therapeutic exercises. An incalcitrant treatment challenge is to support patient compliance and their carryover of behavioral changes outside the clinic. Wearable technology is widely adopted to help track patient’s health conditions and promote adherence to treatment. Existing wearables for VUA health monitoring are, however, wired, semi-rigid and single modal sensing at best. In this project, we will leverage our expertise in wearable electronics, biomaterial engineering and computational medicine to develop a new class of VUA health wearable system. In particular, the new wearable will be wireless and conformable to the neck skin surface. A dual-modal sensing technology, which will be implemented for the very first time in VUA wearables, will be developed with neck surface accelerometry (NSA) and surface electromyography (sEMG). The combined use of NSA and sEMG will offer complementary physiological measurements that will allow for monitoring VUA symptoms with better precision and broader utility. Three specific aims (S.A.) are proposed in this project. S.A. 1. We will develop a single neck-worn wearable device that is skin-conformable, wireless and dual-sensing. A commercial NSA sensor, a multi-channel sEMG array and peripheral electronics will be assembled on a flexible, stretchable substrate. Our team has developed dry, soft sEMG electrodes, which will be customized for detecting perilaryngeal muscle activity. We will implement wireless power management and data transmission protocols. We will further modify our biocompatible and reusable adhesives for long-term wearable mounting. S.A. 2. We will evaluate the new wearable device on vocally healthy participants to optimize the configuration and placement of NSA and sEMG sensors. We will also develop efficient machine learning models to classify VUA symptoms in near real time. Results will help us refine the wearable system toward system miniaturization. S.A. 3. We will develop a companion smartphone application (app) for user-device interaction and data management. We will then evaluate the usability and utilization of the wearable system in patients with laryngeal hyperfunction who will undergo a week of remote monitoring in a free-living setting. Lastly, we will use the collected wearable data to build patient-specific algorithms for estimating clinical VUA symptom severity. Outcomes from this study will allow for iterative product improvement and translation of this technology for clinical use in a rational and accountable way. Ultimately, this wearable system will assist clinicians to remotely track patients’ VUA health status for precision treatment, and more importantly to better engage patients in self- managing their symptoms and create healthier outcomes.

NSF Awards · FY 2024 · 2024-08

The 2015 discovery and ongoing observations of gravitational waves by NSF's Laser Interferometer Gravitational-wave Observatory (LIGO) have transformed mankind's perception of the Universe, revolutionizing modern astrophysics, cosmology, and general relativity. Upgrades to the 4-kilometer LIGO detectors continue to expand their horizons, but LIGO can ultimately only access the local gravitational neighborhood. To achieve a cosmological reach, complement traditional modes of observation, and gravitationally probe the Universe back to its infancy will require larger-scale “next-generation” interferometers. The planned Cosmic Explorer (CE) Observatory, ten times larger than LIGO, will maintain and advance US leadership in this revolutionary new field. However, constructing the 40-km ultrahigh-vacuum (UHV) laser beamtubes needed to realize CE represents a key technical challenge. This award will support the development and testing of scalable technology to implement high-performance, reliable, and economical vacuum beamtubes at the largest physical scale ever attempted, on a timescale compatible with CE construction and observations. By helping to enable CE, the Cosmic Explorer Beamtube Experiment (CEBEX) advances gravitational wave observational science, while projecting novel studies of ultrahigh vacuum environments for physical science research, manufacturing technology, and surface science into new realms. Under this award, the CEBEX team, based at LIGO Hanford Observatory, will design, construct, and test a 1.2m diameter by 120m long prototype UHV beamtube section as a technology pathfinder for the CE observatory. The scale of this activity requires the construction of a purpose-built lab structure on available land at the current LIGO site. Beamtube materials, construction methods, and industrial processes will be implemented and tested to confirm feasibility, scalability, and compliance with CE requirements. In the final year of the planned 4.25-year Award, the team will apply the results of this research to deliver to NSF an efficient conceptual reference design, parametric cost estimate, and schedule framework for CE beamtube construction. These will form key underpinnings of pending future CE design and construction initiatives. 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 · 2024-08

Extremal combinatorics is that part of discrete mathematics that studies how large or small a collection of finite objects can be under given restrictions and has broad connections with number theory, discrete geometry, probability, theoretical computer science and beyond. Recent advances in this area have brought to the fore several unexpected connections between seemingly disparate problems. In this project, the PI will explore some of these connections further to resolve several old problems in the area and forge further connections with other areas. The research will involve graduate students and postdocs. Of particular interest are the recent breakthroughs in graph Ramsey theory and the advance of Mattheus and Verstraëte specifically, which has revealed intriguing connections between the study of off-diagonal Ramsey numbers and problems in extremal graph theory and finite geometry. The PI also intend to build on previous progress by the PI and his collaborators to make further progress in graph Ramsey theory, extremal graph theory and the fundamental areas of additive combinatorics and discrete geometry. In doing so, the PI expects to open further connections and increase interactions between extremal combinatorics and important recent trends in the study of high-dimensional expansion, convex geometry and algebraic combinatorics. 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 · 2024-08

Buoyancy – light warm gas goes up and heavy cold gas goes down – is widely understood as a core principle. The motion of the two fluids is induced by the unstable density stratification (heavy on top of light) and the presence of gravity. As potential energy is converted into kinetic energy, the flow field becomes three-dimensional and random; it transitions to turbulence. Simultaneously, a layer forms between the pure heavy and pure light fluids, where the two fluids mix. These flow instabilities, often referred to as Rayleigh-Taylor instabilities, are found in a large diversity of engineering applications and natural phenomena (inertial confinement fusion, furnaces, fires, heat transfer within stars, supernova formation, underwater hot vents, oil spill, etc.). A lot of research has been done on the initial and long-term growth of Rayleigh-Taylor instabilities; however, little is known about the structure of the turbulence inside these buoyant flows. The main goal of the project is to isolate the specific features that make a turbulent buoyant flow different from regular turbulence. Such understanding will enable new insights into buoyant flows across a wide range of fields. The goal is also to bridge the gap between research and education with activities focusing on middle schools, undergraduate students, and the general public. In order to gain access into the fine details of turbulence, high-fidelity numerical simulations of various controlled experiments will be performed. These configurations will span all regimes of turbulent buoyant flows, from weak buoyancy to buoyancy-dominated turbulence. The dependence of the vertical velocity on the fluid density, which is both a consequence of buoyancy and the mechanism behind Rayleigh-Taylor instabilities, will be extracted from these simulations. Utilizing this dependence, a mathematical framework will be derived to relate any turbulent buoyant flow to regular turbulence. This framework will be leveraged to derive reduced order models specifically designed for turbulent buoyant flows, thus addressing a long-standing deficiency. Finally, the research will validate these new models in simulations of various experiments of increasing complexity, including buoyant plumes and fires. 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 2025 · 2024-08

Project Summary: Monoterpenoid bisindole alkaloids are a broad class of natural products that includes members which have been demonstrated to disrupt protein–protein interactions in human cancer cells. These dimeric compounds consist of two independently biosynthesized monoterpenoid indole alkaloids unified by a C–C bond. Bisindole alkaloids display an assortment of biological activities, such as nitrous oxide synthase inhibition and multidrug resistance reversal, and includes the FDA-approved anticancer drugs vinblastine and vincristine. Despite their potential to serve as pharmaceuticals or lead compounds, there have been relatively few total syntheses of any members of this class; this is due to the challenges encountered with synthesizing the two complex and structurally unique monomers followed by unifying them into a sterically congested product. Furthermore, most approaches to date have relied on biomimetic strategies, which are not amenable to synthesizing analogs to explore the structure- activity relationship of these molecules. The studies described in this proposal seek to develop modular and convergent strategies for the enantioselective syntheses of bisindole dimers and non-natural analogs. The rationale for the proposed research is that efficient access to bisindole alkaloids will increase their accessibility and allow for in-depth biological evaluation. Furthermore, a modular approach can be adapted for the synthesis of analogs to enable structure activity relationship studies into this potent class of molecules. This will be realized through two specific aims centered on the synthesis and evaluation of these complex, biologically relevant molecules. In Aim 1, a robust enantioselective total synthesis of melodinine J, a never-before-synthesized bisindole dimer which has demonstrated cytotoxicity levels similar to the chemotherapeutic vinorelbine, will be developed. The route will feature a Pd-catalyzed asymmetric alkylation and target highly oxidized indole alkaloids, derivatives of which have been implicated to bind to tubulin. The synthesis will expand the scope of the Petasis reaction as a robust means to unite the two monomers in a late-stage, convergent manner. Aim 2 will involve the generation of a library of non-natural bisindole alkaloids to enable biological assays and structure- activity relationship studies. Strategies will be developed for the modular, assembly-line synthesis of analogs that can vary the nature of the linker with fine-tuned precision. This work would positively affect human health by deepening our molecular-level understanding of the roles these potent compounds and their linkers play in mediating biological processes.

NSF Awards · FY 2024 · 2024-07

Studying how the ocean and atmosphere have changed over Earth’s history helps us understand past climate and environment, as well as the development of life. Ancient pieces of ocean floor provide one way to study ancient ocean chemistry as the rocks in them have interacted with seawater. This project will investigate three pieces of ocean floor from a time between 750 million and 2 billion years ago, which is not well understood. Iron, strontium, and oxygen in these rocks will be analyzed to quantify past oxygen levels and the composition of seawater. Additionally, a detailed database of chemical data from ophiolites of all ages will be created for future research. This project supports a graduate student and offers internships to both international undergraduates and high school students from the Pasadena Unified School District. An interdisciplinary workshop will be held to share and synthesize state-of-the-art research and encourage future collaborations. In summary, this research will advance our knowledge of Earth’s early environment, with potential implications for predicting future environmental changes, and support the training of the future scientific workforce. Altered oceanic crust provides an archive to reconstruct the chemical evolution of the ocean and atmosphere over Earth’s history. During formation and cooling, oceanic crust is hydrothermally altered via low- and high-temperature interactions with seawater. These interactions modify the original composition of magmatic crust and provide a record of deep ocean seawater chemistry. Although these alteration processes are well-documented in the modern (through drilled oceanic crust) and Phanerozoic (through ophiolites, or preserved fragments of oceanic crust), the Precambrian record of oceanic chemistry is debated and poorly studied from the perspective of altered oceanic crust. This research will investigate hydrothermal alteration processes in three near-complete Proterozoic ophiolites via systematic sampling and analysis of samples from all stratigraphic levels. Specifically, bulk-rock Fe3+/ΣFe, 87Sr/86Sr, and 18O/16O will be measured to reconstruct past marine O2 concentrations, radiogenic Sr isotopic composition, and O isotopic composition. The sample suites will be archived and made available to future researchers to understand other aspects of Proterozoic marine chemistry. Further, a compilation of all previously published geochemical data on ophiolites (of all known ages) will be produced and made available to the scientific community. This research represents a critical step forward from the current state of limited data for Proterozoic ophiolites and a fragmentary data archive of ophiolite chemistry. 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 · 2024-07

The field of gravitational wave astrophysics is experiencing rapid growth, propelled by advances in detector sensitivity and analysis tools. The ongoing fourth observing (O4) run of NSF's Laser Interferometric Gravitational-wave Observatory (LIGO), Virgo, and KAGRA detectors has brought a significant increase in the detection rate of compact binary coalescences, reaching approximately 0.5/day, compared to 1.5/week in the previous run. This award responds to the data analysis needs of O4 with two projects: ensuring that our measurements are robust against contamination from detector artifacts known as glitches and studying the spins of black holes detected with gravitational waves. The award will support the training of students in STEM areas. The award targets two areas of study under gravitational wave data analysis. The first area concerns the spins of black holes in binaries. Black hole spins carry important information about the astrophysical properties of compact binaries, including the question of whether binaries form through dynamical processes in dense environments or through isolated evolution in the field. The project will constrain the astrophysical distribution of black hole spins in binaries using the few hundreds of events expected from O4. The second area addresses challenges in obtaining robust estimates of the binary parameters in the presence of data quality issues. Previous work led to a method for mitigating detector glitches (non-Gaussian detector noise) that coincide with signals by simultaneously modeling the signal and the glitch and subtracting the latter. The project will apply this method to O4 candidates to obtain robust estimates for the binary properties. 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.