University Of California-Irvine

NSF Awards · FY 2024 · 2024-08

This project will use a state-of-the-art rapid gene evolution system to change relatively simple enzymes into enzymes with advanced capabilities that extend beyond those found in nature. In doing this, this project will help us understand how enzymes upgrade their performance over long periods of time, provide blueprints for enzyme design, and contribute to synthetic biology, and potentially biotechnology, medicine, agriculture and the bioeconomy. Like most processes involving long natural evolutionary timescales, the emergence of complex enzymes from what were presumably simple biocatalysts early in life's history has not been directly observed. The investigators have developed a powerful synthetic evolution system called orthogonal DNA replication (OrthoRep) that drives the in vivo continuous evolution of chosen genes at mutation rates one million-fold higher than those of the host genome. OrthoRep compresses gene evolution processes that naturally take thousands to millions of years into weeks-long laboratory experiments involving just the passaging of cells. The investigators propose using OrthoRep to prospectively evolve “simple” primitive catalysts into “advanced” biological enzymes. The simple catalysts from which we will start evolution are artificial metalloenzymes (ArMs), chosen because they mimic the putative organization of primordial enzymes in early life where catalytic performance is predominantly localized to a cofactor attached to a protein scaffold. They will evolve ArMs into advanced enzymes, guided by the hypothesis that the evolutionary emergence and optimization of interconnected amino acid networks coupling the active site to sectors across an entire protein is responsible for the exceptional performance of modern enzymes. This collaborative US/Switzerland project is supported by the US National Science Foundation (NSF) and the Swiss National Science Foundation (S-NSF), where NSF funds the US investigator and S-NSF funds the partners in Switzerland. Within NSF, the project is co-funded by Office of International Science and Engineering, and the Systems and Synthetic Biology Program in the Division of Molecular and Cellular Biosciences. 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

The primary science mission for radio-based high energy neutrino technology is to search for astrophysical sources of neutrinos with extremely high energies, at least 100,000 times higher than the highest energy particles created by the strongest terrestrial particle accelerators. Observations at this extreme provide insight into the nature of the most extreme particle accelerators in the Universe and may point to the long-sought sources of the highest energy cosmic rays. The NSF-supported ARIANNA collaboration pioneered the development of the surface station architecture for radio-based neutrino astronomy and is thus ideally placed to contribute to multi-messenger science, providing critical capabilities such as excellent pointing resolution and measurement of the neutrino cross-section. This research will create the next generation of trigger technology and will revitalize the successful design and operation of surface station experiments. The project will provide training in both hardware and software to students at both graduate and undergraduate levels, including under-represented groups and women. Such experience will be a valuable asset for future workforce placement. The ARIANNA design relies on the observation of radio emission from neutrino interactions in cold transparent Antarctic ice by radio antennas buried only a few meters below the snow surface, but previously used a very simple scheme to trigger the detector. The next generation of trigger technology will exploit the unique ”chirped” features of the waveforms produced by these shallow antennas by developing an all-digital trigger, so that trigger schemes can access the full data records before creating their trigger event. This new trigger hardware will implement AI tools such as Deep Learning, which work best with unfiltered data directly imported from high speed digitizers. The work will continue a fruitful collaboration with Uppsala University (Sweden). 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

A process of cell competition can remove cells that differ genetically from neighboring cells in the same tissues. Cell competition helps to eliminate sporadic aneuploid cells that have abnormal chromosome numbers. Aneuploidy contributes to almost all carcinogenesis and is a hallmark of aging, contributing to cellular senescence. The current project investigates the mechanisms by which genes that encode ribosomal proteins, by virtue of their wide distribution in the genome and stoichiometric requirement for ribosome biogenesis, are used as sensors for altered cellular chromosome content, using fruitflies as a genetic model system. Importantly, cells with single mutations in ribosomal protein genes can also be recognized and removed from developing tissues by the process of cell competition with nearby normal cells, related to the elimination of aneuploid cells. This project will further define the molecular mechanisms of cell competition pathways by gain and loss of function genetics targeted specifically to aneuploid cells within otherwise normal tissues, and characterize the alterations in gene expression that result from cell competition on a single cell level. The relationship of specific chromosome gains and losses to tumor formation will be defined. The mechanisms whereby the p53 protein protects the genome from progressive genome damage, and the route by which genomic changes accumulate in the progression towards cancer, will be elucidated. These studies aim to define the molecular basis for the cellular recognition and elimination of aneuploid cells in developing tissues, its role in maintaining genome integrity at the tissue level by selection against abnormal cells, and its role in tumor surveillance and the development of cancers.

NIH Research Projects · FY 2025 · 2024-08

PROJECT SUMMARY/ABSTRACT Down syndrome (DS) is a developmental genetic condition caused by trisomy of human chromosome 211-6. DS occurs in approximately 1 in 600-1000 live births and affects more than 300,000 individuals in the USA. Neuropathological and clinical features of Alzheimer’s disease (AD) present early in life through the seventh decade in a predictable sequence of events, and include amyloid plaques, neurofibrillary tangles, nerve growth factor (NGF) dysmetabolism and cholinergic basal forebrain degeneration, CNS inflammation, and cognitive decline1-10. DS is an outstanding natural genetic model for the study of AD pathophysiology, AD biomarkers research and to conduct preventive clinical trials. Despite the molecular and genetic similarities between AD and DS, there exists a paucity of information on the biological mechanisms underlying the onset of cognitive decline in adults with DS. For this INCLUDE application, our overall goal is to investigate DS-specific pathophysiological mechanisms of AD and identify novel biomarkers within and outside of the AT(N) framework, with a special focus on immune and NGF dysregulation at different stages of AD pathology in DS by capitalizing on the ongoing highly successful collaboration between our teams: Jorge Busciglio (University of California, Irvine, USA), Claudio Cuello (McGill University, Montreal, Canada), Thomas Wisniewski (New York University, NY, USA) and Juan Fortea (Hospital of Sant Pau, Barcelona, Spain)7-9, 11, 12. We propose to test the central hypothesis that CNS inflammation and NGF metabolic dysfunction are early and key pathophysiological mechanisms leading to neurodegeneration, accelerated aging and cognitive decline in DS. As detailed below, we will utilize a novel approach combining unbiased discovery (transcriptomics and proteomics) (Aim 1) and targeted biomarker analyses (Aim 2), using multiple complementary model systems, to establish a model of the temporal relationship between immune and NGF dysregulation and AD-related neurodegenerative changes in persons with DS (Aim 3). This will be achieved by correlating our findings with AD pathology, related biofluidic and imaging biomarker data from among the largest well characterized, DS patient population found globally. We propose the following 3 aims: Aim 1: To elucidate the relationships between immune deregulation and NGF dysmetabolism with AT(N) hallmarks in the DS brain and in human trisomy 21 cortical cultures. Aim 2: To investigate the presence of immune dysregulation and NGF dysmetabolism markers in plasma and CSF and in extracellular vesicles derived from brain tissue, primary cultures and body fluids across the AD continuum in DS. Aim 3: To establish the temporal ordering of immune dysregulation and NGF dysmetabolism with respect to the AT(N) framework within a cohort of adults with DS assessed longitudinally with multimodal biomarkers. The comprehensive combination of neuropathological, cellular, and clinical studies using the same biomarkers will lead to a detailed characterization of the role of immune and trophic factor alterations in the development of AD pathology and associated cognitive decline in DS. Guided by the INCLUDE initiative goals, the results will inform future preventive trials and assist in the prediction of the onset and evolution of AD dementia and in the identification of potential novel biomarkers and therapeutic targets in this vulnerable population.

NSF Awards · FY 2024 · 2024-08

The movement of ions through tiny structures, called channels, with openings 100,000 times smaller than the thickness of the human hair is the basis of all physiological functions of a living organism. Due to their small scale, the building blocks that form the channels are subject to constant changes, leading to fluctuations in the channels’ opening. These ever-present changes in shape are a crucial feature that allows many biological channels to fulfill their functions. Inspired by biology, this project proposes a set of universal guidelines to create nanopores as a model system that mimics biological channels by fluctuating in similar dimensions and timescales. Reproducing fluctuations of biological channels in model systems will allow the researchers to understand transport properties on the nanoscale, and to harness new transport properties that will result from these dynamic systems. This research project will provide multidisciplinary training for undergraduate and graduate students. Moreover, the scientific findings of this research will be shared with broader audiences through creative communication methods that are designed in collaboration with the University of California, Irvine Claire Trevor School of Arts Department of Drama. This project aims to design solid-state nanopore systems whose local pore openings are subjected to controllable fluctuations, of set amplitude and frequency reaching hundreds of MHz up to GHz, using electromechanical gates in the form of DNA and proteins. The nanopores will be prepared based on sandwich structures of silicon nitride/gold/silica, where the thickness of each component will be tuned with sub-nanometer precision. To render the diameter dynamic, the researchers will attach DNA and proteins that bind adenosine triphosphate (ATP) to the gold layer. The conformational state of the molecules will be dynamically tuned with voltage and ATP in the solution, and the effective local pore diameter and its fluctuations will be determined. Pores with dynamic openings will be characterized for their ability to enhance ionic and molecular transport, pump ions against their concentration gradient, and distinguish between ions of the same charge. The expected outcome of this project is to establish the optimal frequency range of diameter fluctuations for each of the transport properties. Due to the high surface-to-volume ratio of nanopores, such fluctuating interfaces are expected to significantly affect mass transport and achieve enhanced fluxes as well as ionic selectivity. 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

This award is funded by the Major Research Instrumentation Program and managed by the Division of Chemistry. Professors Potma and Fishman from the University of California, Irvine (UCI), on behalf of 20 investigators in 8 different departments across the university, are acquiring an optical photothermal infrared (OPTIR) microscope system. This new type of microscope makes it possible to visualize a wide range of samples, from biological tissues to polymers to novel micro-structured materials. The images produced with the OPTIR microscope platform reveal the molecular content of the samples using contrast derived from the sample’s specific chemical bond vibrations. This unique system will support cutting-edge scientific programs at UCI, foster research collaborations with California State University Fullerton, and accelerate collaborative projects with industry partners. In addition, the requested instrument will be incorporated into several graduate courses and will play a critical role in a diversity-enhancing summer program. Microscopic imaging based on chemical bond vibrations permits the interrogation of samples without using extrinsic labels. Vibrational microscopy is an indispensable tool for the chemical analysis of micro-structured samples, from biological specimens to engineered and self-assembled soft matter systems. Commercial vibrational microscopes fill an important need, yet limitations in imaging speed, spatial resolution, and sensitivity have hampered their implementation in a wider range of imaging applications. The recently developed OPTIR microscope has overcome such limitations as it enables sensitive, background-free vibrational imaging based on mid-infrared absorption at sub-micrometer resolution. These new capabilities will be leveraged to drive advanced research programs in biological materials, including the development of mid-infrared tags, chemical mapping of skin and bioprosthetic heart valves, identification of therapeutic agents in brain tissues, and chemical analysis of cells in microfluidic devices. The system will also propel research projects in the area of soft materials, exemplified by label-free imaging of coacervates, self-assembled elastic networks, crystallin proteins of the eye lens, aerosol particles, and microdroplets. Furthermore, the OPTIR microscope will open new doors in the field of micro- and nano-structured solid-state materials, enabling projects focused on structures with infrared-active phonon polaritons, low-dimensional condensed materials, two-photon polymerized microstructures, as well as cerium oxides. 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

ABSTRACT: This U01 application aims to (1) develop a robust protoacoustic dosimeter for 3D in vivo dosimetry in proton FLASH therapy, which is essential for its clinical application and acceptance; (2) form a multi-disciplinary and multi-institutional research partnership, incorporating both academic and industrial entities, to hasten the creation and implementation of this innovative dosimeter for clinical usage in the ensuing 5-10 years. More than half of cancer patients receive radiation therapy (RT) in their treatment journey. The recent RT method, FLASH, using an ultra-high dose rate, is noted for its ability to minimize normal tissue damage while maintaining tumor control. Proton therapy is emerging as a promising delivery method for FLASH. Ensuring the precision of proton FLASH delivery is critical given the high risks of such treatments. Errors in ultra-fast delivery can significantly affect dose delivery to the tumor and healthy tissues. As a result, there's an urgent need for a 3D in vivo dosimeter for validation and guidance of the actual dose delivered by FLASH. This necessity stems from the fact that current dosimeters can't handle the ultra-high dose rate in FLASH or lack in vivo volumetric data. Thus, developing 3D in vivo dosimetry is key for the precise delivery of proton FLASH RT. Our proposal involves the creation of a novel Protoacoustic/Ultrasound Dual-modality Imaging System (PUDIS) to meet this pressing need. PUDIS uses protoacoustic imaging for dosimetry validation, and we are pioneers in exploring radiation-induced acoustic imaging for radiation dosimetry. Recently, we've shown the potential of using protoacoustic signals for in vivo dosimetry of a single proton pulse. However, more work is needed to explore this technology under FLASH dose rate and significantly enhance the image quality for precise 3D dosimetry. We aim to accomplish this through the following objectives: Aim 1: Characterize the basis of protoacoustic imaging as a FLASH dosimeter on human-size phantom. Aim 2: Develop a robust protoacoustic/ultrasound dual-modality imaging system (PUDIS) for dosimetry/anatomy verification on animal models in vivo. Aim 3: Establish PUDIS as a quantitative 3D dosimetry system for FLASH therapy. Outcome/Impact: This grant will result in a rigorously vetted PUDIS prototype, marking the first introduction of 3D in vivo dosimetry to proton FLASH RT. Backed by a team of cross-institutional academic and industry experts, we anticipate a successful project. PUDIS's in vivo 3D dose verification will catalyze precise proton FLASH RT, unlocking FLASH's full potential. This accelerates research, application, and acceptance of this treatment, ultimately benefiting cancer patients vulnerable to RT-related toxicities.

NSF Awards · FY 2024 · 2024-08

NON-TECHNICAL SUMMARY: The main goal of this project is to find a practical and scalable way to recycle mixed plastic waste. Most plastics do not mix well, making it hard to recycle them using current methods. Traditional recycling methods are designed for specific types of plastics and do not work well for mixed plastic waste. Although there have been some new recycling techniques, none have successfully solved the problem of mixed plastic waste. To address this, two new methods will be investigated, both making use of a special type of chemistry that can form and break bonds easily. Method 1 will introduce chemical bridges between different plastic types while they are being melt processed together, facilitating them to stick together better. Method 2 will use pre-made materials that mechanically interlock different plastic molecules during melt processing. Both methods are designed to work with diverse type of plastics, making them potentially applicable for recycling various plastics together. If successful, this project could introduce a new universal strategy for recycling mixed plastics together, helping to reduce the global problem of plastic pollution. The proposed study will provide great opportunities to train graduate and undergraduate students, including minority and women students working on this project. TECHNICAL SUMMARY: The primary goal of this project is to develop a practical and scalable approach for the universal compatibilization of polymers, facilitating the recycling of mixed plastic waste. The inherent immiscibility of most plastics poses a significant challenge to mechanical recycling efforts. Traditional compatibilization methods, tailored to specific polymer compositions, are impractical for addressing mixed plastic waste. Despite the emergence of various innovative recycling methods, an effective solution for recycling mixed plastic waste remains elusive. To tackle this challenge, this project will investigate two innovative compatibilization methods, both based on dynamic covalent chemistry. In Aim 1, a robust dynamic covalent crosslinking chemistry will be developed to efficiently introduce dynamic crosslinks during melt extrusion, chemically connecting different polymer chains as in situ-formed compatibilizers. In Aim 2, pre-made vitrimers will be explored as compatibilizers for immiscible polymer blends, creating mechanical interlocks during melt extrusion. Both approaches share the distinctive feature of independence from specific polymer structures, potentially offering universal applicability for compatibilizing diverse plastics. This project aligns with the CAS-CS focus on “Developing enhanced methods for recycling and upcycling of chemicals and materials, especially as related to circular technologies”. If successful, the project could introduce a new, universal strategy for polymer compatibilization, addressing the global environmental challenge of plastic pollution through the recycling of mixed plastic waste. The proposed study will provide great opportunities to train graduate and undergraduate students, including minority and women students working on this project. . 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

With support from the Improving Undergraduate STEM Education: Hispanic-Serving Institutions (HSI Program), this Track 2 project aims to enhance student engagement in office hours within STEM courses, particularly focusing on biology courses at multiple HSIs and emerging HSIs within Southern California. Office hours are a common resource for student learning and represent a space where students can engage with other students and instructors. However, office hours remain underutilized by STEM students. The “hidden curriculum”, a set of unspoken norms, practices and values that influence academic success, compounds disparities in office hours attendance and engagement, exacerbating retention and graduation gaps of all students. Thus, this project will examine office hours practices and develop evidence-based interventions that can reduce disparities in office hours engagement. Such efforts will positively impact retention and persistence within STEM by creating structural changes to better support student engagement and success. The project unites a network of seven Hispanic Serving Institutions (HSIs) and emerging HSIs, including both 2-year and 4-year colleges within Southern California. The specific aims of the project are: 1) characterize student and faculty perceptions of office hours; 2) investigate the impact of different office hours practices on student behavioral, cognitive, and affective engagement; 3) identify factors that promote office hours engagement; and 4) design and assess evidence-based interventions aimed at increasing student engagement in office hours. We will conduct surveys and focus groups for students (including students who have and have not attended office hours) and instructors to gather insight into student perceptions, motivations, and barriers as well as instructor perceptions and practices. We will form a collaborative learning community across our network that will use data gathered to design evidence-based interventions to foster office hours engagement. Through application of our findings, we will create and disseminate evidence-based practices for faculty that support student engagement in office hours. Because of the ubiquitous nature of office hours, our interventions will be applicable to instructors across institutions and STEM fields, and we will lead workshops and develop evidence-based teaching guides to share our work. Thus, our project will promote student success and belonging in STEM for all students across higher education through structural changes that support student engagement. The HSI Program aims to enhance undergraduate STEM education and build capacity at HSIs. Projects supported by the HSI Program will also generate new knowledge on how to achieve these aims. 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: This proposal outlines a new investigator grant (NIBIB Trailblazer R21) for the PI to develop a new holographic platform that enables high-speed, noninvasive 3D chemical imaging with broad biomedical applications, including analysis of tumor microenvironment and real-time imaging of live cell cultures/animal models/engineered tissues. While nonlinear optical microscopy is an attractive approach because it is label-free, nondestructive, and offers higher resolution and richer information than linear microscopy, it usually involves 3D scanning that limits the imaging refresh rate. To obviate this bottleneck, recent research has sought to combine nonlinear optical microscopy with digital holography to vastly improve imaging speed. However, current implementations either lack chemical selectivity or require tuning the laser wavelength in order to measure vibrational spectra. To achieve a deeper understanding of biomedical processes at the molecular level, there is clearly a significant need to further improve imaging speed and obtain rich spectral information. The long-term goal is to develop a new nonlinear digital microscopic holography approach capable of high-speed 3D imaging with spectroscopic vibrational contrast: i.e., 5D imaging in spatial, temporal, and spectral dimensions, in live cell cultures and animal tissues. This transformational tool will enable discoveries of disease mechanisms and new treatment paradigms. This application’s objective is to demonstrate the feasibility of a new approach to achieving time-domain hyperspectral microscopic holography through vibrationally resonant (VR) sum-frequency generation (SFG) and third-order sum-frequency generation (TSFG). Using mid-infrared photons to resonantly excite vibrational modes will enable chemical mapping of different functional groups in specimens, while the nonlinear processes offer submicron resolution. Combining SFG and TSFG in one instrument will enable multimodal probing of non-centrosymmetric sample components as well as other components. Hyperspectral holography will enable 3D imaging and simultaneous recovery of the signal field’s amplitude, phase, and spectral frequency in a single time scan. Three specific aims will be pursued: Aim 1 is to demonstrate hyperspectral VR-SFG microscopic holography and validate its performance. Based on comparison to the phase-sensitive multiplex VR-SFG microscopy previously demonstrated in the applicant’s hands, a single holographic interferogram can be measured with a 4-μs exposure time and a signal-to-noise ratio of 10, with further improvement in signal-to-noise ratio expected. Aim 2 is to demonstrate multimodal VR- SFG/TSFG and to accelerate the acquisition rate by ~10x via compressive sensing. Aim 3 is to expand the spectral range to the fingerprint region through building a new mid-infrared light source. The approach is innovative because it integrates concepts in a new unproven format for imaging with unprecedented speed and vibrational spectroscopic contrast. The proposed research is significant because it is expected to vertically advance nonlinear digital microscopic holography for chemical mapping with submicron/subcellular resolutions.

NIH Research Projects · FY 2025 · 2024-08

PROJECT SUMMARY/ABSTRACT The long-range goal of this research is to explore how HIV-1, when suppressed by anti-retroviral therapy (ART), sustains the immune activation and consequent accelerated aging that underlie the survival gap between people living with HIV (PLWH) and the general population. HIV-1 itself is likely a key driver of immune activation. However, in the setting of low levels of virus replication, it is unclear how HIV-1 continues to cause inflammation. We propose that monocyte activation by immune complexes (ICs) made of Gag, HIV-1 RNA, and anti-Gag IgG contribute to chronic inflammation and endothelial cell dysfunction in ART-treated PLWH. This notion arises from our preliminary data indicating that nucleic acid-containing ICs stimulate monocytes in vitro to produce inflammatory chemokines. Such ICs are likely to be present in ART-treated patients whose viremia is well controlled, because in addition to replicating virus, genomes of defective virus—which makes up >90% of the reservoir virus in treated patients—can transcribe RNA and encode Gag. Moreover, most individuals maintain anti-Gag antibodies despite undetectable plasma viremia. Consistent with the idea that nucleic acid-containing ICs promote immune activation is the intriguing observation that natural hosts of SIV, who resolve immune activation, have very low or undetectable anti-Gag antibodies, whereas such antibodies are readily measured in pathogenic SIV infection of macaques. In addition, patients with autoimmune disorders such as lupus, make IgG that binds to nucleic acids or to ribonucleoproteins. Like PLWH, patients with lupus have endothelial cell dysfunction and accelerated atherosclerosis. Analogous to what we propose for IgG-Gag-RNA ICs, nucleic acid- containing ICs in lupus are internalized by phagocytes through Fcγ receptors (FcγRs) where they engage TLRs and mediate inflammation. To test the hypothesis that ICs consisting of Gag, RNA and anti-Gag IgG mediate immune activation, we will accomplish two specific aims: Aim 1: Measure the inflammatory response to nucleic acid-containing ICs in healthy, human FcγR-transgenic mice. Mice will be treated with HIV-1 Gag (p55, which contains the RNA-binding domain NCp7) and HIV-1 RNA with or without anti-Gag human IgG1. Markers of immune activation and microbial translocation will be measured. Specific Aim 2: Using human vascularized micro-organs (VMO's), assess interactions between nucleic acid-containing ICs, monocytes, and endothelial cells (ECs). Since endothelial dysfunction plays a role in diseases contributing to mortality in ART-treated PLWH, we will use VMOs to assess the impact of ICs and monocytes on the vasculature. VMOs (three dimensional models allowing physiological flow, EC function and gene expression) will be treated with monocytes and ICs, and vascular permeability, cytokine expression, and in situ expression of adhesion molecules will be measured. The proposed research is designed to determine whether or not nucleic acid- containing ICs drive the immune activation and endothelial dysfunction that contribute to reduced life expectancy in PLWH. Novel therapeutic strategies to provide a functional cure for HIV may emerge from our research.

NIH Research Projects · FY 2025 · 2024-08

Imaging early development of human neural circuits The overall objective of this research is to create new imaging technology that dramatically improves our ability to analyze the development of brain function and functional networks before birth. Functional magnetic resonance imaging (fMRI) provides a unique capability to study neural circuits and brain functional connections in-vivo. Fetal fMRI acquisition and analysis, however, has been hampered by three important challenges: 1) fetal motion disrupts the spatial and temporal continuity of the MRI signal, 2) geometric distortion is exacerbated by the motion of fetal and maternal organs, and 3) the anatomy and function of the developing fetal brain is distinctly different from those of young children and adults, thus current processing pipelines and atlases are inadequate for reliable fetal fMRI analysis. To address these challenges, we pursue three specific aims in this study, that are focused on 1) developing a prospectively motion navigated fetal fMRI acquisition technology, based on fast real-time image processing, that compensates for the fetal head motion and geometric distortions during acquisitions; 2) developing a post-acquisition processing technique that reconstructs an fMRI time series from motion- corrected fetal fMRI data that are scattered in space and time because of motion and motion correction; and 3) assessing the utility of fetal fMRI and the developed technologies to evaluate early development of neural circuits and brain function in fetuses with congenital heart disease compared to healthy fetuses. This contribution is important because it 1) mitigates a critical barrier to making progress in the field of developmental neurology and neuroscience by allowing reliable use of fetal fMRI in studying normal vs. abnormal development of the brain function; 2) improves the efficiency and efficacy of fetal fMRI through prospectively adjusting scans to compensate for motion and geometric distortions, thus strengthens our ability to study large cohorts; 3) provides tools and resources, including atlas-based parcellation and a processing pipeline for the analysis of fetal fMRI; and 4) generates important knowledge about the origins of disrupted neural development due to hypoxia ischemia in congenital heart disease. The technology, resources, and knowledge developed in this study have a broad impact and are crucial for advanced studies in developmental neuroscience and neurology, aiming to elucidate the potentially devastating effects of adverse early life conditions including congenital disorders of the brain and heart. It is hoped that these studies lead to improved understanding of the underlying causes of neurodevelopmental disorders, leading to preventive strategies, therapies, and in some cases, cure.

NIH Research Projects · FY 2025 · 2024-08

PROJECT SUMMARY Rare diseases have a negative impact on the quality of life of patients, who are left on the road of a psychologically challenging, expensive and uncertain diagnostic odyssey that sometimes lasts years. In many cases, patients receive multiple wrong diagnoses in the interim and may miss windows of intervention. Our proposal leverages the broad clinical, research and data science expertise at UC Irvine (UCI) and Children’s Hospital of Orange County (CHOC) in conjunction with Ambry Genetics’ expertise in clinical testing and infrastructure to provide affordable and comprehensive evaluations for patients with undiagnosed diseases as well as several Community Health Partners with access to medically underserved populations. The result will be an academic + non-profit + community + commercial partnership based in Orange County that will serve as a regional hub covering a large US Southwestern area within the national UDN. The Southern California UDN (SoCal UDN) site will be built on the foundation of the existing UCI/CHOC Diagnostic Center of Excellence, which is able to collect in-depth phenotype and genotype data in a sustainable fashion by performing studies on a clinical basis whenever possible and collaborating with existing translational research studies for genomics, research phenotyping, or functional evaluations. Our partnership with Ambry will further allow research genomic data to be generated from clinically covered exome sequencing. This proposal will promote rapid expansion of our program. Through partnerships with regional tertiary medical centers with whom we have a history of collaboration, we will bring UDN expertise and resources to patients throughout the American Southwest that would not otherwise have access to a local UDN clinical site, facilitate appropriate evaluation prior to acceptance, and avoid unnecessary travel for clinical phenotyping studies. We will work with community partners to improve equity for underserved populations in our region including the economically disadvantaged and Vietnamese Americans. To improve efficiency and promote sustainability, we will leverage the extensive machine learning and AI infrastructure at UCI to include machine-assisted subject identification, informed consent, record review, data management, and result disclosure into our workflow. By participating in the larger UDN, we will facilitate data and sample sharing in a way that will improve the understanding of rare diseases and advance the diagnostic process for patients with previously undiagnosed diseases.

NIH Research Projects · FY 2025 · 2024-08

An estimated 6.5 million Americans over the age of 65 live with Alzheimer’s disease, a progressive neurodegenerative disorder with no effective cure and the leading cause of dementia worldwide. Dementia is typically preceded by a prodromal phase of Mild Cognitive Impairment (MCI), in which the earliest observed cognitive changes are in memory. Research shows that up to 40% of dementia risk is due to modifiable risk factors including sleep and cardiovascular risk factors that exacerbate Cerebral Small Vessel Disease (CSVD). CSVD is found in approximately 80% of patients with concomitant Alzheimer’s disease pathology and represents early, subtle changes to the cerebrovascular system. Taken together, the interplay of sleep and CSVD is understudied, particularly in the context of Alzheimer’s disease-related cognitive changes in older adults. The overall goal of this proposal is to examine the mechanisms linking CSVD to sleep-dependent memory deficits seen in Alzheimer’s disease and to underscore the most relevant features of sleep that most robustly predict CSVD. The Specific Aims address the role of CSVD in sleep-dependent memory deficits by investigating fronto-temporal gray matter structure and local sleep expression as possible mechanistic links. The present study design allows for a detailed characterization of participants across clinical and cognitive domains. Participants undergo (1) magnetic resonance imaging (MRI), (2) two weeks of wrist-worn actigraphy, (3) an overnight in-lab polysomnography study with high-density electroencephalography (hdEEG) and (4) a memory task delivered in a sleep-dependent manner. This innovative, multi-modal study design has not been widely implemented in older adults and lends to the applicant’s training goals of using advanced computational and statistical methods to analyze high-dimensional datasets. This project will spearhead the applicant’s career goals of becoming an independent investigator, utilizing computational methods to study biomarkers of neurodegenerative disease. This project targets NIH’s goals for sleep research, including investigation of sleep mechanisms underlying disease and risk reduction. UCI is an ideal institution to enact these study aims, as it is a world-class research institution with modern neuroimaging facilities and a culture of collaboration. The applicant has support from two experts in the fields of sleep research, Alzheimer’s disease, basic memory science, and neuroimaging techniques. Collaborators listed on this proposal will provide additional support for assessment of clinical factors, hdEEG, and statistical modeling. Insights from this proposal will fill in two major gaps in our knowledge: (1) what features of sleep most strongly predict CSVD burden, and (2) what mechanisms link CSVD to sleep-dependent memory in older adults. This project may reveal new therapeutic targets for behavior-modifying interventions in sleep, inform precise screening in patients with disordered or deficient sleep, and shape public health recommendations as the number of Americans impacted by Alzheimer’s disease is projected to double by 2050.

NSF Awards · FY 2024 · 2024-08

An important motivation for the research of the PI is to understand the relationship between the geometry and the topology of a space. The latter, topology, is the study of properties of a space which are invariant under continuous stretching or bendings of a space, while the former, geometry, involves understanding distances and is more rigid. For example, the surface of our planet is a sphere, and one measures distances on it by computing arclengths of great circles (the Earth is actually an oblate spheroid, but it is very close to being perfectly spherical). One can imagine deforming the Earth by pushing in or pulling on small or large regions to warp the geometry. Such a deformation is less appealing that the familiar round Earth, and there are many ways to make this notion very precise in terms of minimizing some sort of total energy measurement. This is directly related to physical principles which say that the state of a physical system will tend towards a final configuration which minimizes the total energy. This idea can be generalized to higher-dimensional objects called manifolds, which are generalized versions of the surface of our planet. For example, the space that we live in is three-dimensional, and if one includes time, we are in a four-dimensional universe. In order to understand these types of higher-dimensional objects, one attempts to find the best way to measure distances on them which use the least amount of energy, and maximize the symmetries of the space. The projects supported by this award are to define appropriate energies on such spaces, and to seek out the important optimal geometries which minimize the total energy. The PI is committed to integrating research and education and cultivating intellectual development on many levels, and plans to continue to be active in outreach and organization of conferences and other events in the mathematics community. In more technical terms, the research of the PI is, broadly speaking, to use solutions of partial differential equations which are geometric in origin to study properties of differentiable manifolds. The main areas of concentration of the PI's research are the classification of gravitational instantons in dimension four, understanding Gromov-Hausdorff limits of Einstein metrics in the collapsing case, and the study of higher-dimensional complete non-compact Calabi-Yau structures. The PI has contributed to the classification of gravitational instantons in dimension 4, and plans to further investigate the global structure of the moduli spaces of these metrics. The PI has also contributed to the classification of asymptotically Calabi Calabi-Yau structures, and plans to study other types of complete non-compact Calabi-Yau structures in higher dimensions. The PI has contributed to the understanding of Gromov-Hausdorff limits of Calabi-Yau metrics on compact manifolds, and plans to further study global properties of compactifications of such moduli spaces. 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

Super-Kamiokande (SK) is a world leading particle physics experiment studying neutrinos, which are subatomic particles that are produced naturally (e.g. in stellar cores and cosmic ray interactions with the earth atmosphere) as well as artificially (e.g. in nuclear reactors and dedicated neutrino beams using particle accelerators). This project focuses on neutrinos from non-accelerator sources, in particular solar neutrinos, neutrinos from supernova explosions, other possible sources of cosmic neutrino neutrinos, and reactor neutrinos. The research impacts particle physics as well as astrophysics. The research will involve and be used in the education and training of graduate, undergraduate and K-12 students. It is also of interest to a next-generation neutrino detector called Hyper-Kamiokande which is currently under construction in Japan. The research uses new methods of identifying neutrino interactions from unfiltered detector data such as machine learning and high data volume processing thereby training students in this important emerging field of computer science. A previous NSF grant supported the design, construction, and installation of a new trigger system, the Wideband Intelligent Trigger (WIT) in the Super-Kamiokande detector as well as analysis of its data. WIT completely processes all off the data in the un-triggered, raw stream and extracts electrons with high efficiency down to 2.49 MeV, the limit of stable and reliable event reconstruction at Super-Kamiokande: the group searches and reconstructs potential candidates in each data block independently to reduce background, processing time and final data size to a manageable level. Using WIT, UCI has identified solar neutrino interactions at lower energies than before in SK (below 3.49 MeV). Such neutrinos are less susceptible to the “MSW effect” than higher energy solar neutrinos. UCI is studying the validity and details (such as energy dependence) of the MSW effect. SK has now been upgraded by dissolving Gd2(SO4)3, to enhance its neutrino detection capabilities. Previously, neutrons in SK were observed by the 2.2 MeV gamma emitted from capture on Hydrogen after about 200 micro-seconds. On average there were only seven detected photons, and the detection efficiency was quite low. Now, after the upgrade, about 50% of the neutrinos will capture on Gd which makes an 8 MeV gamma cascade and produces about 22 detected photons per capture after about 35 micro-seconds. UCI created a data sample below 100 MeV with the most sensitivity to search for neutrinos coincident with supernovae in nearby galaxies, gravitation wave detections, gamma ray bursts, and high-energy neutrinos. We expect large improvements in the sensitivity of such searches from our current program to further reduce the background from cosmic ray muon-induced spallation. This data sample also searches for the “diffuse sea” of neutrinos emitted by all supernovae up to a red shift of about 1. The improved neutron detection efficiency improves the separation from supernova anti-neutrino interactions from background. The award is aligned with the NSF Big Idea of Windows on the Universe: the Era of Multi-messenger Astrophysics as it coordinates the use of multi-messengers observations utilizing cosmic neutrinos and providing alerts to the larger community. 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

Early childhood years are critical for developing the foundational knowledge, skills, and attitudes for later success in STEM. Young children learn science best when they actively engage with topics that are meaningful to their everyday lives. Artificial intelligence can help in developing science learning content and making it more interactive, while also presenting the challenge - and opportunity - of providing unbiased AI-generated materials. This project involves direct participation from local parents in co-designing these AI-based educational materials. University and community partners will jointly work with AI to create interactive science stories that draw on family values, and everyday experiences, and that are adaptable for families in multilingual contexts. The project leverages storytelling - a major form of social capital in local communities - to foster children's scientific curiosity and engagement, while also helping build community members' AI literacy skills. The project will contribute important knowledge about how AI can be effectively harnessed to support science learning across contexts. The project utilizes participatory design with families in California and Michigan to create 24 e-books for children aged 4-7, employing generative AI for rapid, iterative content development. The e-books will feature an AI-powered conversational agent that allows children to dialogue directly with the story characters, as well as family discussion prompts to encourage parent-child interaction. After the 24 interactive e-books are piloted and iteratively improved, a randomized control trial will be carried out with 120 families to evaluate the impact of e-book use on children's science knowledge and engagement and on parent-child science communication. Subsequent improvements will prepare the e-books for free national distribution. Findings will expand knowledge of how AI-powered storybooks support children's science learning and family interaction, and will inform the design of scalable, language-adaptable tools that can strengthen early STEM education across varied home and school settings. In doing so, this project will also demonstrate pathways for promoting the innovation and use of trustworthy AI in educational technologies. This Integrating Research and Practice Project is funded by the Advancing Informal STEM Learning (AISL) program, which supports research on the development and impact of STEM learning opportunities in informal educational environments. This project is also partially funded by the Innovative Technology Experiences for Students and Teachers (ITEST) program, which supports projects that build understandings of practices, program elements, contexts and processes contributing to increasing students' knowledge and interest in science, technology, engineering, and mathematics (STEM) and information and communication technology (ICT) careers. 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 Child maltreatment is one of the most formidable public health crises in the United States, affecting millions of youth each year. The adverse consequences of maltreatment for youth, as well as for their families and entire communities, are pervasive, costly, and enduring. To intervene and reduce these consequences, it is imperative that victims provide clear and accurate accounts of their prior experiences. Currently, considerable skepticism exists regarding maltreated youth’s ability to provide such accounts, especially for experiences that were stressful, leading to youths’ reports being challenged or not believed. We contend that this skepticism is unwarranted, and maltreated youth actually demonstrate better memory than their non-maltreated counterparts, but only for stressful salient personal experiences. We will ethically and rigorously test this possibility in the proposed study via a short-term longitudinal experimental investigation that compares the effects of acute stress on memory between maltreated and demographically matched non-maltreated 12-17-year-olds. In an initial in-person session, youth will be randomly assigned (equal maltreated and non-maltreated youth across age) to complete standardized salient personal activities that are experimentally manipulated to vary in whether they induce higher or lower levels of acute stress. Immediately afterward, youth will complete an encoding task comprised of positive, negative, and neutral images. In subsequent sessions (two remote and one in person) spanning approximately one month, youth’s memory will be tested for the images via a recognition task asking them to discriminate previously seen from unseen images and for the personal activities via recall and direct questions that probe for the extent and accuracy of memory. Youth’s rumination about the personal activities will also be measured. Our main hypothesis is that maltreatment will lead to particularly robust memory for the personal activities, but only when the youth complete these under conditions of high stress. By contrast, because the emotional and neutral images are not personally meaningful, we expect maltreatment to constrain youth’s memory performance for the images. We also hypothesize that rumination will serve as an important mediator of the links between stress and memory for the higher stress personal activities, most notably in the maltreated youth. Overall, our results will provide much-needed knowledge about the precise ways that maltreatment shapes different facets of youth’s memory, knowledge that will be enormously valuable in improving trust in maltreated youth’s reporting of stressful experiences and hence in directing interventions for victimized youth.

NSF Awards · FY 2024 · 2024-08

The primary goal of this work is to play a leading role in the production of the first scientific results from the Jiangmen Underground Neutrino Observatory (JUNO) and to involve high school teachers and their students directly in this research. Neutrinos are elementary particles that provide insight into the fundamental makeup of our world and the sources that produce them. JUNO is an international experiment featuring a 20,000-ton liquid scintillator neutrino target observed by over 43,000 photomultiplier tubes (PMTs) and surrounded by 35,000 tons of ultrapure water. By studying the disappearance of reactor antineutrinos from eight nuclear reactors at a baseline of about 53 km, JUNO aims to determine the order of neutrino masses and measure three parameters driving neutrino oscillation with approximately one order of magnitude better precision than currently available. JUNO will also break new ground in the search for new physics and the study of neutrinos from the Sun, the Earth, supernovae, and the interaction of cosmic rays with the atmosphere, providing complementary information to that obtained via other channels. The JUNO group at UC Irvine is involved in the construction, commissioning, data analysis, and leadership of JUNO. The group co-leads the installation and commissioning of the 25,600 3-inch “small” PMT system and the efforts to get it ready for physics. The group is also co-responsible for planning and deploying a calibration for the 20-inch PMT system’s instrumental non-linearity using the small PMT system, which will directly impact many of the results released by the experiment. The PI co-convenes the working group responsible for analyzing the rich reactor antineutrino dataset collected by JUNO and its satellite detector, TAO. The UC Irvine group actively participates in this work through the development of its own analysis framework and is preparing to play a leading role in the release of JUNO’s first physics results with reactor antineutrinos, some already expected to achieve world-leading precision. This cutting-edge research will train young scientists from diverse backgrounds and develop expertise in areas of strategic importance, such as nuclear physics, data science, and machine learning. Moreover, high school students and their teachers will engage through activities organized in partnership with the QuarkNet organization, including masterclasses, workshops, school visits, and research internships. 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

Version 1 This project aims to strengthen democracy by offering actionable proposals to address democratic erosion and sinking trust in democratic institutions. While much contemporary scholarship and commentary charts the decline and frailty of democracy around the world, this project asks social science researchers and practitioners from the USA, Europe and Africa to propose solutions and reforms to improve the legitimacy and efficacy of democratic institutions. These proposals will both advance our scientific knowledge of democratic institutions, for example, parties and elections, as well as serve the national interest by proposing ways to improve those institutions for everybody. Version 2 The democratic innovation project is a series of workshops devoted to advancing our knowledge about how to improve democratic institutions. The project focuses on the problem of sinking trust in democratic institutions linked to doubts about legitimacy and efficacy. The overall aim is to connect social science knowledge about political institutions to solutions to political problems. Workshop participants will examine eleven identified institutional contexts to develop both a diagnosis of the problem within that context as well as an institutional reform that can address that problem. 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

Galaxies are made of stars, gas, and black holes. The interaction between these components determines how a galaxy, like our own Milky Way, grows over time. Stars and black holes may change the chemical content of the gas reservoir and/or eject it completely out of the galaxy through winds. The latter outcome, particularly prevalent in interacting galaxy systems, tends to stop future generations of stars from being formed in those galaxies. The investigators will analyze new observations of merging galaxies to trace the movement of gas as it traverses the galactic ecosystem, enabling a detailed understanding of this dynamic process. The investigators will also augment the Observational Astronomy Workshop at Lick Observatory through increasing graduate student participation and by adding a new science communication module to enrich the education and professional development of a diverse range of students. Leveraging new Keck and JWST integral-field spectroscopic observations, the investigators will study the hot ionized and warm molecular gas for a representative sample of galaxy mergers to establish the intricate nature of gas fueling and feedback and its role in galaxy evolution. Outflowing gas masses and energetics will be measured and compared to predictions from the latest feedback models across the temperature--density regimes. Presenting a holistic view of gas dynamics from the dusty nuclear cores out to the circumgalactic medium, this project is extremely timely. 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 · 2024-07

PROJECT SUMMARY/ABSTRACT Pain is a public health problem, a major driver of health care seeking and medication use, a major cause of disability, and a key factor affecting quality of life and productivity. Music-based interventions (MBIs) including music therapy (MT) are known to be effective for managing pain in several populations. However, substantial gaps remain in understanding the mechanisms of action (e.g., cognitive, genomic, metabolomic, and neurologic) by which MBIs influence pain. Barriers to advancing this mechanistic r esearch have included: 1) lack of meaningful and inclusive collaboration between music therapists and mechanistic scientists; 2) inconsistent application and definition of MBIs, patient-reported outcomes, and biological measures; and 3) lack of funding and infrastructure to support interdisciplinary pilot projects. This proposal seeks to establish a NEW collaborative network: Effective Network to advance Scientific Evidence related to Mechanisms of music-Based interventions for pain and support coLlaborative Efforts (ENSEMBLE) to advance collaborative research efforts investigating the mechanisms by which MBIs influence various pain phenotypes. ENSEMBLE will be built on a foundation of well-integrated medical MT practice, strong mechanistic science in integrative health and medicine (IHM), research investigating MT and biological mechanisms of pain in SCD and the BraveNet Practice-Based Research Network. At the outset, SCD will serve as the pain-related condition of interest given the expertise of ENSEMBLE team members at present and strong preliminary data, but other pain conditions will be addressed in future years. ENSEMBLE will be led by investigators from University Hospitals of Cleveland/Case Western Reserve University, University of California Irvine, The Louis Armstrong Center for Music & Medicine, Icahn School of Medicine at Mount Sinai, and Emory University. ENSEMBLE will establish a vibrant collaborative network of music therapists, mechanistic scientists, music intervention researchers, IHM resear chers, and patient-advocacy organizations. The Specific Aims are to: (1) promote meaningful, inclusive, and interdisciplinary collaboration between music therapists, mechanistic scientists, and IHM researchers; (2) develop a comprehensive framework for conducting mechanistic studies in MBIs for pain management; and (3) advance multiple pilot projects investigating novel biological mechanisms of action underlying the effects of MBIs for various pain phenotypes. The IMPACT of ENSEMBLE will be instrumental in 1) promoting meaningful interdisciplinary dialogue; 2) building multi-institutional capacity for initiating MBI research in pain management; 3) generating preliminary data for future R21 or R34 grant proposals; 4) improving data infrastructure; 5) developing future MT clinician researchers; 6) focusing future scientific efforts; and 7) disseminating best practices.

NIH Research Projects · FY 2025 · 2024-07

Our goal is to build the UCI CTSA Hub as an innovative, nimble, and dynamic virtual laboratory that can implement NCATS’s bold vision for translational science. Fueled by unprecedented growth in UCI’s research portfolio, new inpatient and outpatient capacity, and robust collaboration with community stakeholders, our Hub is positioned to profoundly impact the science of translation and public health in our region and beyond. Two formative and synergistic themes guide our Hub’s strategy for the next funding cycle. The first, “From Lab to Life,” was developed by our community partners at the inaugural CTSA funding in 2010 and reflects the seminal and ongoing NCATS’s focus on nurturing the kernels of translational science that can be found in virtually all clinical research. We will catalyze a wide range of basic and applied innovations enabled by unique UCI and community talent, such as: 1) transforming clinical trials in rare diseases, 2) reimagining cell-based diagnostic and therapeutic technologies for a broad spectrum of health conditions, and 3) reconceptualizing the practice of neurorehabilitation through AI-based mechanistic use of haptic robotics. Our second theme, “From Hub to Health,” embraces NCATS’s and our Hub’s burgeoning focus and expertise on bringing new translational science discoveries to clinical practice and benefit of people in our region dealing with a wide range of diseases and health conditions. In preparing “From Hub to Health” objectives, we worked closely with the Orange County Health Care Agency (OCHCA), our county public health department, which serves more than 3.2M people, reflecting the healthcare needs not only in our region but seen across the U.S. The Healthy School Restart Program pioneered data-driven policy guidance for public and private schools during the pandemic and blossomed into a formal Hub-OCHCA collaboration. “From Hub to Health” projects for the next funding cycle are wide ranging and include: 1) the request from OCHCA for the Hub to serve as the translational science collaborator for a regional OC System of Care Think Tank to improve health care delivery in our region, 2) expanding our Hub Medical Student Research Program to achieve unprecedented gains in health science student participation in translational science, 3) leading a novel, nationally funded program to train a uniquely talented workforce in population-health informatics and data science, and 4) re-envisioning design of investigator-initiated clinical trials by developing, demonstrating, and disseminating our program of Quality-by-Design Studios. Our partnerships with UCI-affiliated Children’s Hospital of Orange County and the Long Beach Veterans Administration ensure that these essential populations will be well represented in all Hub activities. The Hub will support these projects by careful allocation of resource modules, training opportunities, and continuous quality improvement with a vigorous application of the translational science benefits model. In sum, we are positioned to promote “more treatments for all people more quickly,” the translational science goal that has guided our Hub since 2010.

NIH Research Projects · FY 2024 · 2024-07

PROJECT SUMMARY/ABSTRACT The Genomics Research and Technology Hub (GRT Hub), the sole UCI genomics shared resource, is applying for support to purchase a Hamilton LiquidScan NGS STAR (STAR). The GRT Hub was founded in 1999 and has served the campus for microarray, DNA genomic analysis and mapping, bulk and single cell RNA sequencing, and most recently multi-omics and spatial transcriptomics. Although physically located in the School of Medicine, the GRT Hub is a short walk from all user schools on the UCI campus. In the last fiscal year, the GRT Hub had $2.13 M in service recharges, the vast majority of which were to UCI investigators. The requested STAR system will automate significant aspects of these next generation sequencing and beadarray workflows, thus providing improved accuracy and reproducibility while relieving the stress of manual tasks currently performed by trained staff. The STAR system will be located within the existing controlled environment GRT Hub space. This workflow modernization is particularly critical with recent increases in throughput for both short- and long-read sequencing platforms and the generous planned UCI campus support for acquisition of Revio and NovaSeq X Plus in 2023 and 2024, respectively. Hamilton is an acknowledged leading manufacturer of robotic systems. The basic unit, the Hamilton STAR, has throughput capabilities for single samples with needle or tip loading and single up to 96 well parallel sample processing. Although every immediate workflow has associated programs, including long and short read sequencing and beadarray as well as a physical module for liquid cell and extracellular vesicle biomarkers, it is also readily programmable. The inclusion of an onboard thermocycler extends the end-to-end processing for next generation sequencing library preparations among other workstreams. This proposal has three specific aims: 1) automate NGS workflows for genomic and transcriptomic library construction to increase efficiency of sample throughput, reduce errors in sample tracking, and increase accuracy and precision in sample processing; 2) increase clinical genomic applications by attracting larger scale projects and developing a specialized unit for biomarker assays; and 3) encourage others to consider modernizing with a robotics training program for facility users.

NSF Awards · FY 2024 · 2024-07

Non-technical description: New functionalities could emerge in quantum materials when different yet related orders coexist, often referred to as “intertwined orders”. An important case is intertwined superconductivity and magnetism that are restricted to two dimensions, such as at the surface or interface. Such a scenario is extremely rare as the conditions for superconductivity and magnetism are usually mutually exclusive, yet the resulting new phases of matter are theoretically predicted to host exotic excitations useful as information carriers in quantum information technologies. In this work, the research team investigates the Fe-chalcogenide superconductors FeTe1-xSex (FTS), where intertwined superconductivity and magnetism have recently been discovered in the surface state. Precision magnetic microscopy and other experimental techniques are used to establish the rich magnetic and superconducting phase diagram, and to search for signatures of the predicted exotic excitations towards applications in magnetic sensing, energy-efficient electronics, and quantum information technologies. This project allows graduate and undergraduate students from underrepresented groups to take part in research and receive trainings in optics, cryogenics, precision measurement electronics, and programming. Through the outreach component, the research team reaches out to middle school students from disadvantaged regions in Santa Ana and motivates them to pursue careers in science and technology. Technical description: Highly correlated condensed matter systems are complex, with coexisting phases that are identified either by the topology of their electronic structure or through the spontaneous breaking of a certain symmetry. This complexity is recognized with “intertwined orders” due to their intimate relations and is technologically important due to the resulting new phases of matter. Of tremendous current interest is the correlated material system Fe-chalcogenide superconductors FeTe1-xSex (FTS) with rich intertwined orders. Using precision magneto-optic Sagnac imaging and transport techniques, the research team has recently established that the surface state is a topological magnetic metal with proximity-inherited superconducting order from the bulk, which remains superconducting but non-magnetic. As such, emerging phases of matter would occur in the surface state with predicted excitations called Majorana zero modes that promise important applications in quantum information technologies. In this project, the research team studies in an interconnected manner three forms of FTS: bulk crystal, exfoliated nano-flake, and atomic layers, to map out the phase diagram of intertwined orders as a function of chemical compositions, structure, and other external stimuli. The obtained information provides the basis for the search for signatures of predicted Majorana zero modes, their propagation at the boundary between adjacent crystal faces, as well as the manipulation of these excitations for potential devices. Through a hands-on outreach program, the research team interacts with students from the local disadvantaged Santa Ana area and motivates them to pursue careers in STEM. 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.