Search Grants — Free, No Account Required

NIH

Significance to VA: According to the Centers for Disease Control and Prevention, female infertility is a major health problem and affects about 6-10% percent (~7.5 million) of women at the reproductive age in the United States. The infertility rates for women Veterans is greater than the general population and is also greater than age-matched active duty women. This translates to well over 100,000 female Veterans. The issue of infertility in Veterans is recognized by the recently introduced Veterans Infertility Treatment Act of 2023 (HR 544) requiring VA to furnish infertility care to veterans and their partners. Ovarian senescence begins about age 30 and over the next 10 to 15 years is manifest by infertility and decreased steroid output. Although ovarian aging is a natural physiological process, cessation of ovarian function at midlife increases susceptibility to the development of co- morbidities, such as osteoporosis, which decrease quality of life and increases healthcare burden. There is currently no intervention for infertility or preventing/delaying the cessation of ovarian function, thus, highlighting an unmet need for novel approaches to tackle this problem. Innovation and impact: Innovation lies in the use of aging ovary models: granulosa cells recovered from young and older reproductive aged women and mice. Innovation lies in the context of understanding the actions of hCG in the aging ovary. Innovation is also derived from our ability to obtain and analyze granulosa cells from patients that have good or poor responses to IVF stimulation, which would facilitate patient phenotyping and personalized treatment plans. Innovation lies in the application of state-of-the-art multi-omics approaches, RNA-seq, CUT&RUN, and ATAC-seq, on matched samples to identify differential binding patterns of selected transcription factors and to profile chromatin accessibility between young and advanced reproductive aged women in response to hCG. The approach will identify and test new candidate genes as potential targets to improve fertility. Specific aims: (1) Determine the transcriptional programs in granulosa cells of young and advanced reproductive age mice and women. We hypothesize that key transcriptional regulators (YAP1 and TAZ) are differentially regulated during aging. We also hypothesize that genomic occupation of YAP1 and TAZ is altered in granulosa of patients who are good responders and poor responders to ovarian stimulation for IVF. (2) Identify and determine the role of hCG-responsive, YAP- and TAZ-target genes in granulosa cells of young and advanced reproductive age mice and women. We will test the hypothesis that YAP1-specific and TAZ- specific target genes will have distinct roles in modulating granulosa cell function. Furthermore, we propose that hCG-mediated, TAZ-responsive genes will improve the health and differentiation of aging granulosa cells, whereas hCG-mediated, YAP1-responsive genes will promote proliferation. Methodology: This project makes use of in vivo aging mouse models using granulosa cells recovered from young and older reproductive age women and mice. We will employ multi-omics (CUT&RUN, ATAC-seq, and RNA-seq) on the same samples to determine and validate specific gene targets to improve the diagnosis and treatment of infertility in women. Path to translation/implementation: This study impacts the VA-ORD Translational Pipeline (TP) Stages T0-1, Disease Biology / pathology (Foundational Studies), T0-2, Target Identification, Evaluation & Efficacy (Proof-of-Concept Studies) and T0-3B, Validation of biomarkers in different populations. We anticipate discovering unique differences in the actions of hCG in granulosa cells as a function of age and patient IVF response. This research will identify and validate new targets, which will facilitate patient phenotyping based on patient age and response. Next steps are to employ in vivo preclinical models using small molecule inhibitors to demonstrate efficacy for improvement of ovarian function and fertility.

Lima/Allen County Foundation

Lima/Allen County Foundation ($75M in assets) supports nonprofits in OH through grants focused on education, community development, health, arts. Awards range from $1,000 to $25,000.

National Institutes of Health

The Instrumentation Grant Program for Resource-Limited Institutions supports the purchase of state-of-the-art scientific instruments to enhance the research and educational missions of resource-limited institutions. Requested instruments may support biomedical research and education in basic, translational, biomedically-related behavioral or clinical fields. This is a Notice of Funding Opportunity (NOFO) for a Limited Competition that will invite application(s) from eligible organization(s) to apply. Please see Section III. Eligibility for additional information. In accordance with NIH standard peer-review processes, the application(s) will be peer-reviewed, and only meritorious application(s) will be considered.

National Institutes of Health

The Instrumentation Grant Program for Resource-Limited Institutions supports the purchase of state-of-the-art scientific instruments to enhance the research and educational missions of resource-limited institutions. Requested instruments may support biomedical research and education in basic, translational, biomedically-related behavioral or clinical fields. This is a Notice of Funding Opportunity (NOFO) for a Limited Competition that will invite application(s) from eligible organization(s) to apply. Please see Section III. Eligibility for additional information. In accordance with NIH standard peer-review processes, the application(s) will be peer-reviewed, and only meritorious application(s) will be considered.

National Institutes of Health

<p>The NIGMS Mature Synchrotron Resources for Structural Biology program supports mature technologies at synchrotron facilities that provide biomedical researchers with state-of-the-art X-ray beamlines, hands-on user training, and expert assistance to generate and analyze structural biology data. NIGMS intends to reissue a Notice of Funding Opportunity to continue to support these important national resources.&nbsp;</p><p>This is a Notice of Funding Opportunity (NOFO) for a Limited Competition that will invite application(s) from eligible organization(s) to apply. Please see Section III. Eligibility for additional information. In accordance with NIH standard peer-review processes, the application(s) will be peer-reviewed, and only meritorious application(s) will be considered<i>.</i></p><p>&nbsp;</p>

National Institutes of Health

The NIGMS Mature Synchrotron Resources for Structural Biology program supports mature technologies at synchrotron facilities that provide biomedical researchers with state-of-the-art X-ray beamlines, hands-on user training, and expert assistance to generate and analyze structural biology data. NIGMS intends to reissue a Notice of Funding Opportunity to continue to support these important national resources. This is a Notice of Funding Opportunity (NOFO) for a Limited Competition that will invite application(s) from eligible organization(s) to apply. Please see Section III. Eligibility for additional information. In accordance with NIH standard peer-review processes, the application(s) will be peer-reviewed, and only meritorious application(s) will be considered.

NIEHS - National Institute of Environmental Health Sciences

Lipoprotein-mediated Nanoplastic Uptake and Transport Across the Placenta Project Summary/Abstract: Micro and nanoplastics (MNPs), are increasingly pervasive in our environment. Microplastics are typically defined as plastic particles smaller than 5 millimeters (5mm), while nanoplastics are even smaller, measuring less than 1 micrometer (1 µm) Originating from the degradation of plastic materials entering our landfills, oceans, and water sources, micro and nanoplastics pose significant concerns for human health. Recent research has expanded its focus on investigating the interactions between microplastics and human placenta, with the understanding of the pivotal role that the placenta has in fetal health and development. This study introduces a groundbreaking perspective aimed at addressing the substantial knowledge gap present about how microplastics translocate into placental tissue and the critical role that chylomicrons may have in facilitating this process. The working hypothesis is that chylomicron-mediated microplastic uptake compromises placental barrier function, leading to the accumulation of microplastics within the placenta and ultimately alters barrier function and cellular response. Utilizing state-of-the-art quantitative methods in previous studies, we have established that the average human placenta at full term contains 130ug/g of total plastics, predominantly comprising polyethylene (53%), polyvinylchloride (10%), and nylon (8.7%). The combination of the prior and this proposed study promises to significantly advance our understanding of the intricate interactions of microplastics, placental function, and fetal development. By gaining a broader understanding of the crucial role of chylomicrons in facilitating microplastic uptake and the consequences, thereof, this research will guide how potential mitigation of microplastic contamination may play a role on maternal and fetal health outcomes.

NCI - National Cancer Institute

PROJECT SUMMARY / ABSTRACT Malignant pleural mesothelioma (MPM) presents a significant challenge in oncology due to its rarity, lethality, and heterogeneity. This complexity necessitates the development of innovative therapeutic strategies, particularly in light of the partial effectiveness and resistance issues associated with current immune checkpoint inhibitors (ICIs). Our research addresses these challenges by focusing on the identification and validation of liquid biomarkers to enable personalized treatment strategies and improve patient outcomes in MPM. Recent advancements in ICIs have offered new hope, with monotherapy showing about a 20% objective response rate, which can be significantly improved with combination therapies. However, resistance to these treatments remains a substantial barrier, affecting approximately two-thirds of MPM patients. We have identified key prognostic factors such as tumor PD-L1 expression, which is associated with unfavorable survival after conventional treatment without ICIs, and the beneficial impact of tertiary lymphoid structures, immune triads, intact 9p21.3 loci, and low soluble mesothelin-related peptide (SMRP) levels on ICI response. We propose a dual-aim research strategy to address the urgent need for precise biomarkers in MPM treatment. Aim 1 focuses on validating the combined utility of MHC genotype and SMRP levels to stratify patient survival and monitor disease progression, employing a predictive model validated through a cohort of over 400 MPM patients. Aim 2 seeks to elucidate the mechanistic connections between liquid multiomics profiles and the tumor immune landscape, using state-of-the-art technologies to identify and verify novel biomarkers and therapeutic targets. This integrative analysis of immune genotyping and circulating proteins aims to accurately map the tumor immune landscape, guiding the development of biomarker-driven therapeutic strategies. By leveraging liquid multiomics for molecular profiling, our project stands to significantly deepen the understanding of MPM biology, identify clinical-grade liquid biomarkers for treatment response prediction, and advance precision oncology. Our multidisciplinary team, with expertise spanning basic to translational research and advanced immunology, is uniquely positioned to make impactful contributions to precision cancer therapy for MPM. This research promises not only to enhance the precision and efficacy of MPM care but also to set new standards in the management of this challenging disease, marking a significant step forward in the pursuit of personalized oncology solutions.

NIGMS - National Institute of General Medical Sciences

This proposal requests funding for a Liquid Chromatography-Mass Spectrometry (LCMS) system to support biomedical research and educational initiatives across East Tennessee State University's Academic Health Science Center. The instrument will primarily serve researchers and students in the Colleges of Medicine and Pharmacy, while remaining accessible to investigators from the Colleges of Public Health and Arts and Sciences. The acquisition of this LCMS system addresses a critical infrastructure gap that emerged in 2022 when the university's previous LCMS instrument became non-functional. From 2009-2022, LCMS capabilities at ETSU facilitated significant research productivity across multiple investigative teams, resulting in over 40 peer-reviewed publications. This research spans an array of biomedical applications including: pharmacokinetic studies of therapeutic drugs and substances of abuse; development of novel drug delivery systems; quantification of endogenous biomarkers in disease states; stability studies of compounded pharmaceuticals; analysis of environmental contaminants; and investigation of lipid mediators in cardiovascular disease. This productivity has been severely hampered by the lack of this essential analytical capability since 2022. Beyond supporting faculty research programs, this instrument will provide exceptional educational opportunities for a broad spectrum of students, including PharmD, MD, PhD, MS, and undergraduate trainees. Hands-on training with sophisticated LCMS technology will equip these learners with specialized analytical skills highly valued in both academic and industrial research settings. This training represents an uncommon opportunity, particularly for undergraduate science students, enhancing their competitiveness for advanced educational programs and future employment. The strategic placement of this instrument within our shared research infrastructure will maximize its impact, supporting ongoing NIH-funded investigations in areas including pharmacokinetics, drug metabolism, natural product chemistry, biomarker discovery, and neonatal abstinence syndrome research. Additionally, the instrument will enable new collaborative research directions that align with institutional priorities in addiction science, infectious disease, and rural health disparities. In summary, this LCMS system will rejuvenate research capabilities that previously flourished at ETSU, while simultaneously enriching the educational experience of our student population in the biomedical sciences.

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT Antiretroviral therapy (ART) is remarkably successful at preventing AIDS but is unable to cure HIV infection due to a durable pool of latently infected cells carrying integrated HIV provirus. The persistence of this latent reservoir contributes to a growing population of people living with HIV whose lifespans are shortened by non-AIDS co- morbidities of chronic infection and in whom HIV infection can reactivate upon ART interruption. Selective targeting of the latent HIV reservoir is difficult due to the absence of either detectable viral antigens or cell- surface markers that would reveal viral reservoirs to the immune system. Alternative strategies to reactive latent HIV in these cells and promote susceptibility to immune attack are not sufficiently robust to facilitate elimination of an adequate quantity of the reservoir to achieve cure. Latent provirus in ART-treated HIV-1-infected patients highly enriched in a heterogeneous pool of CD4 T cells exhibiting variably elevated expression of sets of cell surface proteins, including programmed cell death-1 (PD-1) and very late antigen-4 (VLA-4). We believe that logic-gated chimeric antigen receptors (CAR) can be developed to facilitate highly selective killing of cells with these combination of markers (AND gate targeting of cells co-expressing PD-1 and VLA-4, for example) while sparing important uninfected immune effector cells with the similar features (NOT gate to prevent killing of CD8+ T cells). This strategy would permit virus-agnostic eradication of sets of cells with defined phenotypic features that encompass most latently infected cells. Such a strategy could be employed in the context of effective ART to shrink the viral reservoir to a level that can be restrained by antiviral immune responses to facilitate drug-free remission. In this proposal, we will build these CAR molecules and test their ability to durably endow human NK cells with highly selective functional activity against discrete subsets of T cells. In addition, we will characterize the expression of the targeted combination of receptors on latently infected tissue T cells. These studies will provide compelling evidence of the feasibility of these logic-controlled CAR regimens and validate a set of target markers in a pre-clinical latency model. These data will facilitate more advanced preclinical testing in non-human primates, humanized mice, and bona fide reservoir cells from people living with HIV.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY/ABSTRACT Advancements in neuroscience, including magnetic resonance imaging (MRI), have significantly improved our understanding of opioid use disorder (OUD) and brain function, yet due to the heterogeneity in the disorder and complexity of the brain, controlled comprehensive approaches in heterogeneous populations are a necessity to characterize individual variability. Here, longitudinal multi-parametric MRI is proposed to assess brain features associated with OUD in genetically heterogeneous stock rats sourced from the NIDA-funded Rat Oxycodone Biobank (U01DA051937), which provides rats with fully characterized genome and addiction-like behaviors, going through a state-of-the-art pipeline with escalation of oxycodone intake following extended access to intravenous oxycodone self-administration. Leveraging features from structural, diffusion, and functional MRI, our investigation seeks to capture the individual differences in the brain, at baseline before oxycodone exposure (Aim 1: pre-existing), and following the oxycodone extended self-administration paradigm during acute withdrawal (12 h) (Aim 2: oxycodone- induced), within the same rats that show vulnerability or resilience to developing oxycodone addiction-like behaviors. We hypothesize that there will be an interaction between the results from both aims. The I/START R03 proposal will allow for the introduction of MRI imaging into the PARC research environment, as a for the PI new, clinically relevant approach, which will complement her current preclinical work with single- cell whole-brain imaging and simplify the translation of the findings for human applications. The collaborative pilot with the Rat Oxycodone Biobank thus aims to set up the basis for larger follow-up studies that will allow for the generation of a heterogeneous, high-quality imaging dataset that will be made publicly available and complement already extensive genomic and behavioral characterization in the same animals. This data will significantly contribute to our understanding of the variable impact of opioids on the brain and individual differences in vulnerability to OUD, providing a unique opportunity to disentangle pre-existing differences from those that are a consequence of exposure to oxycodone. Ultimately, this research seeks to pave the way for improved prevention and personalized treatment strategies, thereby reducing illness and disability associated with OUD.

NIDCD - National Institute on Deafness and Other Communication Disorders

Project Summary Deaf children remain at elevated risk for persistent language delays with downstream impacts on literacy and health, even with newborn hearing screening and early intervention. Most signing deaf children move through early grades without consistent discourse-focused sign language intervention. This project will establish the first prospective, multi-site longitudinal cohort of signing deaf children followed systematically under Strategic and Interactive Signing Instruction (SISI), an intervention that develops sign language discourse and then guides translation into written English. This focus is motivated by large-scale longitudinal spoken-language research showing that discourse is a distinct dimension that uniquely predicts later literacy above and beyond vocabulary and grammar; the present study extends this principle in sign language. Approximately 500 children (ages 4-10; PreK-Grade 3) will be tracked for four years across 20 programs for the deaf. The study has three aims: (1) model growth trajectories in sign language development across ages 4-10; (2) test whether growth in sign language predicts growth in written language; and (3) identify child- and intervention-level moderators (e.g., language background, additional disabilities, dosage and fidelity) that accelerate or constrain growth. Children will contribute language samples twice annually in narrative, informational, and persuasive discourses, scored with the Sign Language Complexity Assessment (SLCA) and a parallel writing assessment. SISI fidelity will be monitored three times annually via video-recorded sessions scored with the SISI Fidelity Tool. Growth will be estimated with state-of-the-art longitudinal models. By establishing discourse-based benchmarks for expected growth, clarifying bilingual pathways, and identifying modifiable factors that shape outcomes, the study will enable earlier, more effective intervention, reducing the effects of language deprivation, and improving literacy and health.

Louisiana Community Foundation

Louisiana Community Foundation ($100M in assets) supports nonprofits in LA through grants focused on education, community development, health, arts. Awards range from $1,000 to $50,000.

Dept of the Army -- Materiel Command

**PLEASE REVIEW FULL SPECIAL NOTICE** Funding Opportunity Title: Low-Cost Chip-Scale Atomic Clock (LC CSAC) Funding Instrument Type: Technology investment agreement The aim of this Special Notice under the ARL BAA (W911NF-17-S-0003), under Grants.gov Opportunity W911NF-17-S-0003-SPECIALNOTICE-LC-CSAC, is to fund a team or multiple teams to design, manufacture, and deliver a battery-powered atomic clock that achieves identical (or better) size, weight, and power (SWaP) and performance to the commercially available chip-scale atomic clock (CSAC) with a selling price goal of < $300/unit in high volume. Precise timing is critical for numerous Army applications such as navigation, communications, surveillance, and synchronization of sensors and systems. Assured PNT solutions currently rely on acquiring GPS signals, which may not be readily available in increasingly contested environments. Commercially available silicon MEMS and quartz oscillators (TCXO, OCXO) are unable to provide GPS holdover in the event of a GPS outage, except for high-end OCXOs that may be considered large and power hungry for certain applications. To ease reliance on GPS, long-holdover clocks with SWaP-C appropriate for various DoD platforms are necessary to enable mission-critical functions even in contested environments. Current high-performance atomic clocks (maser, laser-cooled cesium fountain) serve as standards and are large, expensive, and require regular monitoring and exquisite environmental control. Since the early 2000s, the chip-scale atomic clock (CSAC) has been developed and successfully matured into a commercial product with DARPA and industry investment. While an Army/Air Force/OSD Manufacturing Technology effort further reduced the manufacturing cost1, the current selling price is still prohibitive for high-volume, low-SWaP DoD platforms. There is an opportunity to leverage the many advances in MEMS, photonics, and atomic physics over the past two decades to develop state-of-the-art, high-performance, battery-powered atomic clocks with improved manufacturability, significantly reduced cost, and improved performance. This special notice seeks proposals from one or more for-profit firms in accordance with 32 CFR 37.210. A consortium, led by a for-profit firm, is also encouraged. Points of Contact: Jonathan Hoffman jonathan.e.hoffman.civ@mail.mil Jenna Chan Jenna.f.chan.ctr@mail.mil

LTX Space Planning Committee

The LTX Space Planning Committee will lead a process to envision and gather input about the future development of a cultural space for Seattle's Latinx community. Community conversations incorporating arts activities will take place between winter 2017 and fall 2018. A multi-disciplinary planning team including a design professional will report on the findings of the outreach.

OD - NIH Office of the Director

PROJECT SUMMARY/ABSTRACT This proposal requests the purchase of a LUMICKS C-Trap Edge instrument for a Major User group at the University of Utah. C-Trap Edge is the first and currently only truly correlative tweezers-fluorescence system combining four core technologies: dual-trap continuous-wave optical tweezers, 3-color TIRF/widefield microscopy, label-free IRM, and intuitive software driven ultra-stable multi-channel micro-fluidics system with automated pressure-driven laminar flow. All combined, the system enables high-resolution single-molecule force- fluorescence measurements with greatly enhanced throughput. Single molecule force and fluorescence spectroscopies have revolutionized cellular and molecular biology, biochemistry, biophysics, and biomedical engineering studies to answer key biological and health-related questions. Currently, these tools are mainly restricted to laboratories with dedicated specific expertise and that have lab-built single molecule instruments. The C-Trap is designed as a turn-key system that allows laboratories without single molecule force or fluorescence spectroscopy expertise to perform state-of-art single molecule force, position, and fluorescence localization and FRET analysis at unparalleled spatial and temporal resolution. Importantly, the intuitive instrument and software interface and automation capabilities will allow non-expert users to run experiments and collect high-quality data after minimal training. The proposal is being submitted on behalf of eight Major Users (all with NIH R01 or R35 funding), who will utilize the bulk of the instrument time, and six Other Users (also all with NIH R01 or R35 funding). These Users represent six departments – Biochemistry, Chemistry, Physics, Microbiology & Immunology, and Mechanical Engineering at the University of Utah, as well as Chemistry & Biochemistry at Utah State University – and span multiple institutions across the state, including the University of Utah and Utah State University. The C-Trap will significantly advance the NIH funded projects of these researchers by enabling high impact single molecule mechanobiological and fluorescence studies on a range of scientifically important biomedical questions in areas or mechanical tension sensing, membrane remodeling, cell motility, nucleic acid packaging and processing enzymes, cell-cell interactions, and protein folding dynamics. The Major Users and technical advisors have extensive relevant expertise with the technology to provide guidance to all Users. The University of Utah are committing significant institutional resources (dedicated space and operating, service, and maintenance funds) to ensure sustained and effective use. The establishment of resource will significantly enhance numerous research programs at University of Utah and contribute to discovery of high impact scientific, biomedical and health-care related knowledge.

Belltown Community Center Super Heroes

Celebrating the Lunar New Year, artists will be featured in a 2-month-long exhibit with accommodating themed workshops tailored at makers, artists, and Asian culture. A gallery showroom at Slip gallery, 2301 1st Avenue, will feature an ongoing exhibition with Asian American artists living in Seattle and the surrounding local area. The gallery will be open regular hours during these months, and the gallery will be open during the Belltown Art Walk on January 13th and February 10th from 6-9PM. This project will be completed by March 31, 2023.

NHLBI - National Heart Lung and Blood Institute

Nucleic acid-based interventions have shown incredible growth over the last several years, especially with the advent of mRNA-based vaccines and new siRNA therapeutics. While this new class of medicine represents revolutionary progress, several shortcomings have been identified. Nucleic-acid based vaccines and their delivery systems can be highly-inflammatory. This may be advantageous in the context of vaccine applications, but can detrimental for therapeutics that require repeat administration, especially for inflammatory diseases. Systemically administered RNA interventions are largely hepatotropic, making effective targeted tissue delivery difficult outside of the liver. Without specific tissue or cellular targeting, many disease states remain impossible to address either because the nucleic acid intervention cannot reach the target efficiently or, if delivery is non- specific, lead to dose-limiting off-target effects. The lung, for example, is a highly desirable target for nucleic acid delivery for the litany of conditions that remain without treatment, such as acute respiratory distress syndrome/acute lung injury (ARDS/ALI), pulmonary hypertension, and fibrosis. However, a highly inflammatory drug substance would result in severe adverse effects due to the delicate nature of the organ. These disadvantages highlight the need for further research and development of nucleic acid carriers that can be formulated to reach specific tissues and cells where they can deliver payloads with surgical precision. Tiba’s approach to non-viral RNA delivery exploits a proprietary delivery system that is a potent alternative to current state-of-the-art lipid nanoparticles (LNPs). This chemical delivery platform, RNABL™, employs a unique RNA nanoparticle carrier technology based on dendritic aminoalkyl-branched lipidoids. Tiba Biotech has developed an extensive library of novel delivery materials and formulations that enable efficient extrahepatic delivery and avoid dose-limiting inflammatory effects that present a challenge to traditional LNP-based systems. Unlike competing polymeric systems, Tiba’s platform is also fully biodegradable and molecularly defined. The project proposed here aims to further advance the therapeutic application of a subset of RNABL delivery materials that exhibit highly specific siRNA transfection in lung tissue when administered intravenously. Preliminary studies have established that endothelial cells are the primary site of uptake, and transfected siRNA can alter protein expression when using these optimized formulations, making them an appealing target site of action for novel vasoprotective biologic treatments. To meet the need for improved, lung specific nucleic acid carriers, we proposed a three-part, in vivo project to: 1) identify the optimal RNABL formulation for selective siRNA delivery to lung endothelium; 2) test the knockdown potency of leading candidates targeting CD31 expression in the lung; and 3) determine the clinical potential of this knockdown approach using an LPS ARDS/ALI mouse model targeting a known mediator of disease progression, NOX4.

LVMH Foundation

Funds environmental sustainability, biodiversity, and arts through luxury group philanthropy.

Arnault Foundation

Supports arts, culture, education, and community development through luxury industry philanthropy.

M&T Bank Foundation

Supports community revitalization, workforce development, and arts in the Northeast and Mid-Atlantic.

NLM - National Library of Medicine

PROJECT SUMMARY Spatial omics is the new frontier in biotechnology – a series of innovations over the last ten years that give us exquisitely detailed views into molecular events and interactions inside cells, across all cells in a tissue sample. Some of these technologies can reveal a complete map of gene transcripts inside each cell and such “subcellular spatial transcriptomics” (SST) technology has immense and widely recognized potential for biomedical applications. Yet, current uses of this technology typically aggregate the available information at the level of an entire cell, rarely exploring the richness of subcellular information available from the assay. This project's goal is to develop a comprehensive toolkit for analyzing subcellular spatial transcriptomics (SST) data, extracting interpretable biological patterns and testable mechanistic insights into tissue function and pathology. The proposed approach will employ innovative spatial analysis techniques, leveraging state-of-the-art machine learning methods and robust statistical procedures. A major thrust will be on identifying subcellular spatial patterns involving individual genes, gene pairs and modules of genes, while being aware of biological variations from cell to cell. A new functionality in the toolkit will be to quantify changes in genes' subcellular distribution patterns between conditions, paving the way to a novel class of biomarkers. Planned approaches will build on recent publications from the PI's laboratory, improving the statistical power and scalability of state-of-the-art tools and exploring complementary modeling techniques. Another major goal will be to describe the subcellular space in useful ways, such as partitioning a cell's landscape into functionally distinct components, annotating axons and dendrites in brain data, and representing each cell's spatial transcriptome in a format that lends itself to machine learning algorithms. Tools developed for this goal will facilitate more accurate discovery of interpretable spatial patterns, charting of intercellular communication in brain SST data, and machine learning-based characterization of cells, ultimately leading to new ways of describing disease and biological conditions. The third plank of the proposed project is to discover how functional patterns at the subcellular level are encoded in gene sequences. For this task, machine learning tools will be implemented that relate gene sequence patterns to gene transcript distribution inside cells, and the discovered sequence patterns will then point to key regulators of those genes, thus providing potential targets for intervention. All functionalities of the proposed toolkit will be subjected to rigorous testing for robustness and reproducibility, and then applied to SST data sets from diverse biological systems, demonstrating their real-world utility. Furthermore, special attention will be given to software and data sharing, through adherence to “FAIR” (findable, accessible, interoperable, reusable) principles popularized by the NIH. This project will not only establish SST analytics on a firm footing, it will also generalize to other “omics” assays of subcellular resolution, that are under development today.

Madison Community Foundation

Madison Community Foundation ($350M in assets) supports nonprofits in WI through grants focused on education, community development, health, arts. Awards range from $2,000 to $100,000.

Maine Arts Commission

Arts Learning grants support K-12 schools and educational organizations integrating arts into curricula, bringing teaching artists into classrooms, and building sustainable arts education partnerships throughout Maine.