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National Institutes of Health

<p>This Notice of Funding Opportunity (NOFO) announces the restructured Shared Instrumentation Grant (SIG) Program that consolidates three existing shared-use instrumentation programs, i.e., the Shared Instrumentation Grant program, the High-End Instrumentation Grant program, and the Basic Instrumentation Grant program. The NOFO invites applications from groups of NIH-supported investigators to purchase or upgrade a single item of state-of-the-art commercially available instrument or an integrated instrumentation system. The instruments purchased through the SIG Program require to be optimally shared among the users to ensure efficient and cost-effective research operations, enable rigorous and reproducible measurements, and encourage collaborative research and benefit broad research communities at large. The minimum award is $300,000. There is no cap on total cost of the instrument; however, the maximum award is $5,000,000. Cost sharing is required for premium instruments or special use instruments.&nbsp;</p>

Sikh Foundation International

Supports Sikh studies programs at universities, Sikh art preservation, and educational materials about Sikh heritage and culture.

Sikh Foundation International

Supports Sikh studies at universities, art preservation, and educational materials about Sikh heritage and culture worldwide.

Silicon Valley Creates

Project and operating grants for arts organizations and individual artists from Silicon Valley Creates. Supports visual, performing, literary, and media arts.

Sioux Falls Area Community Foundation

Sioux Falls Area Community Foundation ($400M in assets) supports nonprofits in SD through grants focused on education, community development, health, arts. Awards range from $2,000 to $100,000.

NIA - National Institute on Aging

Project Summary Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of hyaline cartilage lining articular joints. A critical challenge for OA management is the development of an effective treatment that reverses cartilage damage. Our previous work indicates the existence of adult skeletal stem cells (SSCs) in postnatal cartilage. These SSCs are dormant yet can potentially repair damaged cartilage when stimulated by surgical procedures such as Microfracture (MF). While MF typically results in the formation of inferior fibrocartilage, we have demonstrated that MF-activated tissue-resident SSCs can be expanded and directed towards the formation of healthy chondrocytes and hyaline cartilage to regenerate full-thickness cartilage defects by pharmacologically modulating SSC activity and the microenvironment surrounding them. This method we termed Growth-factor Enhanced Microfracture (GEM). Our published studies and preliminary data demonstrate that GEM works well in young animals but is less effective in aged mice. Our data supported by recent findings of others further suggest that FGF7 (Fibroblast Growth Factor 7) expression in the SSC lineage is induced by an inflammatory aged and osteoarthritic bone marrow niche, which leads to pro-fibrotic lineage-skewing resulting in cartilage loss. We now build on additional preliminary results showing that direct and indirect blockade of FGF7 during GEM can reinstate stem cell-based cartilage formation in joints of aged and OA mice. The gained insights from the proposed study will help us to develop strategies to efficiently apply GEM even in impaired settings with a cellular microenvironment less conducive to articular cartilage regeneration. To that end, we are elucidating the cellular dynamics and molecular mechanisms that underlie SSC mediated cartilage repair. In Aim 1, we will expand our preliminary findings to confirm and mechanistically dissect how inhibiting FGF7 locally during GEM in aged and osteoarthritic mice can promote hyaline cartilage formation. In Aim 2, we will determine if epigenetic rewiring of local SSCs by a novel therapeutic compound is sufficient to overcome age-related impairments of GEM mediated cartilage regeneration. Our experiments will use state-of-the-art structural and functional readouts at the tissue level as well as latest technology to unravel cellular and molecular changes at the single cell level to assess regenerative properties and provide new biological insights into OA. Our team brings together expertise in skeletal stem cell biology, in-depth basic science and clinical knowledge of OA as well as bioengineering competency. We are using cutting-edge methods to pursue hypothesis-driven questions aimed at unlocking endogenous stem cells for cartilage repair. By taking advantage of a therapeutic window to skew local MF-activated SSC fate we want to generate new cartilage for the resurfacing of OA joints independent of age and disease state. Eventually, we wish to translate these preclinical studies.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY: SKIN-TARGETED METAL-ORGANIC FRAMEWORK-BASED SUBUNIT VACCINES Driven by their affordability, manufacturability, and safety benefits over traditional vaccines, subunit antigens are an important component of modern vaccinology. However, they exhibit poor immunogenicity and efficacy, and thus, new and rational strategies are required to improve their immunogenicity and efficacy. We propose a novel skin immunization platform (SIP) to address the limitations of vaccine development with subunit antigens. Our innovative and globally deployable SIP leverages emerging vaccine technologies, including (1) metal-organic framework (MOF) nanovaccine constructs; (2) a clinically de-risked adjuvant, and (3) needle-free, thermostable, and self-applied microneedle arrays (MNAs), as well as highly immunoresponsive skin niche for the development of effective and accessible subunit vaccines. The central hypothesis of our project is that in situ harnessing of the immunologically rich milieu of skin with our SIP in a spatially and temporally controlled manner will drive the generation of robust, durable antigen-specific humoral and cellular responses in a well-tolerated manner. Our SIP is engineered in the form of rapidly separable MNAs (rsMNAs) that consist of high-quality obelisk-shaped microneedles comprising dissolving polymer matrix tips loaded with MOF vaccine constructs and non-dissolvable stems with filleted bases attached to the backing layer. Unlike traditional MNAs that require relatively longer wear times (minutes), our rsMNA design, which is enabled by the unique ability of biodegradable MOFs in protecting vaccine components against denaturing organic solvents needed to form non-dissolvable stems of microneedles, facilitates the implantation of MOF vaccines into the skin in less than 10 s via shear force. Our SIP offers the superior vaccine delivery and immunogenicity characteristics compared to needle-and-syringe (N&S) vaccines and conventional MNA-based vaccines. As such, our SIP unlocks the true potential of the skin immune system for improved cutaneous vaccination strategies with subunit antigens. Ultimately, this project will yield a rapidly translatable SIP that will provide unparalleled flexibility and efficacy for vaccination with subunit antigens, which is unattainable with the state-of-the-art immunization platforms.

SODEC

SODEC supports Quebec's cultural enterprises including film, television, music, publishing, and performing arts through grants and financing programs.

OD - NIH Office of the Director

ABSTRACT/SUMMARY This proposal requests funds to purchase a Liberty Blue 2.0 solid-phase peptide synthesizer. At present, Vanderbilt lacks a comparable capacity for customized peptide synthesis, compelling researchers to rely on commercial vendors. While standard peptides can often be sourced at reasonable cost, the synthesis of peptides incorporating non-proteinogenic amino acids, macrocyclizations, or site-specific chemical modifications incurs prohibitive costs and prolonged lead times. These limitations negatively affect numerous NIH-funded research programs and severely lowers the chemical novelty accessible to investigators who make use of peptides in their research. Acquisition of an institutional instrument will directly address this gap, enabling timely and affordable access to high-quality, customized peptides that are increasingly central to modern biomedical research. This instrument will serve a large and scientifically expansive group of investigators across 15 departments in the College of Arts and Science, the School of Medicine Basic Sciences, and the Vanderbilt Institute of Chemical Biology. Investigators from the Vanderbilt University Medical Center will also have access. The user base spans a wide array of NIH-funded projects that rely on synthetic peptides. For example, one group synthesizes fluorophore-labeled peptides to monitor receptor trafficking. Another develops cleavable linkers that release antibiotics from antibody-drug conjugates designed to target methicillin-resistant Staphylococcus aureus. A third focuses on macrocyclic peptides that modulate the activity of CFTR and thus show promise as future therapeutics for cystic fibrosis. Several other groups engage heavily in structure- and AI-guided design and require rapid synthesis of candidate molecules to support downstream biochemical and cellular validation. The Liberty Blue 2.0, manufactured by CEM Corporation, uses microwave-assisted chemistry to accelerate synthesis cycles, improve coupling efficiency, and enhance overall yield and purity. The instrument accommodates a wide range of chemistries and scales, offering flexibility to support exploratory screening, structure-activity relationship campaigns, and early-stage preclinical development. Importantly, it also provides significant cost and time savings compared to commercial synthesis, especially for chemically complex sequences. The instrument will be housed within the Molecular Design and Synthesis Core, which has provided synthetic chemistry expertise and training to the Vanderbilt community since 2006. This core will oversee daily operation and user access, supported by administrative and financial contributions from the School of Medicine Basic Sciences and the College of Arts and Science. Acquisition of the Liberty Blue 2.0 will significantly enhance Vanderbilt’s infrastructure for chemical biology, lower the barrier to peptide-based experimentation, and accelerate discovery across multiple scientific disciplines and therapeutic categories.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY The project supports ongoing efforts in the Shea group geared at developing new computational methodologies and tools to study the liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs). Biomolecular condensates formed by LLPS play a range of vital physiological roles in the body, but under aberrant conditions, they can transition into amyloid fibrils, a process linked to disease. The project will meld artificial intelligence protein-language models with a multiscale computational framework to accurately simulate the dilute and dense LLPS phases, characterize the role of water, co-solvents, and high pressure in modulating assembly, and identify new LLPS-prone sequences in the human proteome. The proposal consists of three research projects. Project 1 involves the development of a tightly integrated multiscale computational approach bridging the atomistic to mesoscopic time and length scales. The relative entropy approach will be used to generate chemically accurate protein and water coarse-grained models from atomistic simulations, which will be used as input for efficient field theoretic simulations. The latter will be used to generate phase diagrams for the LLPS of the microtubule-binding Tau protein and Elastin-Like Polypeptides (ELPs), with field theoretic outputs backmapped to generate atomistic, solvated condensate structures that can be directly compared to experiment. Project two involves the development of new high pressure Kirkwood-Buff force fields for the osmolyte trimethylamine N-oxide (TMAO) from experimental Kirkwood-Buff Integrals, and their application to the study of TMAO’s counteraction of high-pressure denaturation of ELP condensates. Project 3 involves developing new artificial intelligence protein language model tools to mine the IDRome – the 28k proteome of intrinsically disordered regions – for new LLPS-prone and co-condensating sequences. The research will lead to state-of- the-art computational tools that will be deposited in Github and made freely available to the broad scientific community, to new physical insights into osmolyte and pressure modulation of LLPS, and to the discovery of new LLPS-prone sequences. The research will inform on conditions that promote functional forms of LLPS as well as lay the foundation for rational therapies for condensate-linked diseases.

NINDS - National Institute of Neurological Disorders and Stroke

ABSRACT: SourceSpikeNet – A biophysically grounded AI approach to spike detection in EEG Epilepsy affects approximately 3.4 million Americans, with 40% experiencing seizures despite medication and 50-60% continuing to have seizures after surgical intervention. Electroencephalogram (EEG) detection of interictal epileptiform discharges (IEDs) is crucial for diagnosis, medication selection, and surgical planning. However, current practice relies on subjective, qualitative identification of a small subset of IEDs, with significant inter-reviewer variability. State-of-the-art automated detectors suffer from high false alarm rates, creating an urgent unmet need for precise, objective IED identification. We propose SourceSpikeNet, a biophysically grounded artificial intelligence approach to IED detection that leverages known neurophysiology and electromagnetic physics to improve spatiotemporal accuracy. Our central hypothesis is that a biophysically informed AI can identify IEDs much more accurately than current methods. In Aim 1, we will characterize IED prototype timeseries patterns from 32,433 expert-annotated IEDs using inverse source modeling and self- supervised machine learning. In Aim 2, we will develop SourceSpikeNet by training a deep learning algorithm on an augmented dataset of 3,200,000 simulated spikes from 1,000 uniformly spaced cortical locations. In Aim 3, we will evaluate SourceSpikeNet's ability to detect all IEDs from 2,484 patients' continuous EEG recordings (3-7 days each) and compare comprehensive IED localization to traditional methodology. We expect that SourceSpikeNet will provide superior spatiotemporal localization of IEDs compared to current approaches, with lower false alarm rates and higher spatial resolution. The successful completion of this project will enhance the accuracy of IEDs as a biomarker for identifying seizure foci, potentially enabling higher surgical success rates and improved outcomes for epilepsy patients.

National Lottery Distribution Trust Fund

R2B+ ZAR annually for charities, arts, culture, sport, and the reconstruction and development fund.

South Arts

Project and operating grants for arts organizations and individual artists from South Arts. Supports visual, performing, literary, and media arts.

South Arts

Regional arts grants supporting touring performances, exhibitions, and cultural exchange. South Arts serves multiple states with NEA-funded programs for arts organizations.

South Carolina Arts Commission

South Carolina Arts Commission provides grants to support arts and cultural programming, artist fellowships, arts education, and community-based arts projects across SC.

South Carolina Arts Commission

The South Carolina Arts Commission provides annual operating and project grants to arts organizations statewide, supporting programming in visual arts, performing arts, literary arts, and arts education that enrich communities across the state.

South Carolina Arts Commission

Arts Education grants fund artist residencies, professional development for arts educators, and creative learning projects in South Carolina K-12 schools, expanding access to quality arts instruction for students across the state.

South Dakota Arts Council

The South Dakota Arts Council awards project grants to support arts programming, exhibitions, performances, and community arts activities that increase public access to the arts and strengthen cultural life across the state.

South Dakota Arts Council

Touring Arts grants help bring professional artists and performing arts groups to communities across South Dakota, particularly rural areas, ensuring all residents have access to quality arts experiences regardless of geography.

South Dakota Community Foundation

South Dakota Community Foundation ($400M in assets) supports nonprofits in SD through grants focused on education, community development, health, arts. Awards range from $1,000 to $50,000.

Southwest Washington Community Foundation

Southwest Washington Community Foundation ($75M in assets) supports nonprofits in WA through grants focused on education, community development, health, arts. Awards range from $1,000 to $25,000.

Spartanburg County Foundation

Spartanburg County Foundation ($200M in assets) supports nonprofits in SC through grants focused on education, community development, health, arts. Awards range from $2,000 to $75,000.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT SUMMARY / ABSTRACT Type 1 diabetes (T1D) is caused by T-cell mediated destruction of insulin-producing pancreatic beta cells. While notable progress has been made in predicting and delaying onset of T1D, our limited understanding of the factors that initiate and maintain this autoimmune attack continue to act as a major barrier to further progress. Increasing evidence points to the pancreas itself, including endocrine cells, exocrine cells, and the extracellular matrix, as possible contributors to the pathogenic immune activation. One factor that is known to contribute to immune cell activation, and that is altered in other pancreatic disease including cancer, is protein N-glycosylation, wherein complex carbohydrate chains called glycans are enzymatically attached to specific asparagine (called N-glycans) residues as proteins transit the endoplasmic reticulum and golgi complex. Glycosylation patterns influence protein stability, localization, and receptor binding, which can dramatically alter cell function and intercellular communication. Though the pancreatic glycome has been studied in pancreatic cancer, very little is known about how the glycome changes in diabetes pathogenesis, partially owing to the relative scarcity of appropriate human tissues to study and to the complexity of analysis methods required to measure protein glycosylation. While single cell transcriptomic data shows that expression of many of the enzymes involved in glycosylation are altered in T1D, it remains unknown how the pancreatic glycome changes during T1D pathogenesis, and whether altered glycosylation contributes to changes in pancreatic structure, cell composition, or immune cell infiltration. I hypothesize that N-glycosylation in the pancreas is altered as type 1 diabetes progresses, contributing to changes in immune cell localization and phenotype. I will employ two state-of-the-art imaging technologies to test this hypothesis in pancreas tissues from donors without diabetes, with positive auto-antibodies, or with recent-onset or long-standing T1D: 1) Imaging mass spectrometry will allow comprehensive quantitation of different N-glycans across entire tissue sections and at single-cell resolution, and 2) Multiplex immunofluorescence microscopy (CODEX) will be used to define pancreatic regions of interest and to quantify cell types and subtypes across the same tissue section. In Aim 1, I will test the hypothesis that the pancreatic N-glycome quantitatively changes throughout T1D progression. In Aim 2, I will test the hypothesis that regions of altered N-glycome signature are associated with changes in cellular composition and immune cell phenotypes. Completion of these aims will identify high level changes to post-translational protein processing signatures as T1D progresses. These results will lay the groundwork for future studies into mechanisms responsible for glycomic changes, identification of specific proteins that are affected, and definition of novel glycoprotein signatures that may be promising biomarkers or drug targets.

National Institutes of Health

Through this funding opportunity announcement (FOA), the National Cancer Institute (NCI) invites applications for P50 Research Center Grants for Specialized Programs of Research Excellence (SPORE). The program will fund P50 SPORE grants to support state-of-the-art investigator-initiated translational research that will contribute to improved prevention, early detection, diagnosis, and treatment of an organ-specific cancer or a highly related group of cancers. For the purpose of this FOA, a group of highly related cancers are those that are derived from the same organ system, such as gastrointestinal, neuroendocrine, head and neck, and other cancers. Other programmatically appropriate groups of cancers may include those centered around a common biological mechanism critical for promoting tumorigenesis and/or cancer progression in organ sites that belong to different organ systems. For example, a SPORE may focus on cancers caused by the same infectious agent or cancers promoted and sustained by dysregulation of a common signaling pathway. In addition, a SPORE may focus on cross-cutting themes such as pediatric cancers or cancer health disparities. The research supported through this program must be translational and must stem from research on human biology using cellular, molecular, structural, biochemical, and/or genetic experimental approaches. SPORE projects must have the goal of reaching a translational human endpoint within the project period of the grant.