Search Grants — Free, No Account Required

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Self-reactive B cells must distinguish self from foreign antigens (Ag), mounting immunogenic responses to the latter but not the former. However, the mechanisms they employ to do so are not fully understood. Long-term, we aim to exploit new molecular insight gained by filling this knowledge gap to restore B cell tolerance in autoimmunity, enhance anti-tumor B cell responses to self-like Ag, and optimize host defense. In this proposal, we leverage a unique and modular platform of liposomes decorated with model Ag, enabling independent control of epitope affinity and density. Using this system, we recently demonstrated that such particulate Ag are much more potent activators of B cells than identical Ag in soluble, monovalent form. We found that this stems not merely from avidity but from the ability of particulate Ag to evade inhibitory signaling pathways normally engaged by soluble Ag and mediated by the Src family tyrosine kinase Lyn. Moreover, we discovered that transcriptional programs and B cell functional responses to particulate and soluble Ag diverge markedly; despite an identical epitope recognized by the BCR, we found that particulate Ag produce robust NF- kB activation even in the absence of T cell help, while soluble Ag drive an NFAT-associated anergy program. We propose that biophysical characteristics of particulate Ag display serves as a stand-alone danger signal that evades tolerogenic transcriptional programs and elicits immunogenic responses by B cells. In this grant, we propose to: (1) Identify proximal biochemical pathways downstream of the Lyn Src family tyrosine kinase that enable B cells to distinguish tolerogenic and immunogenic Ag display. We will edit mouse and human B cells in vitro and in vivo to test candidate substrates of Lyn. We will complement this with an unbiased proteomics approach to identify novel negative regulators of B cell responses to self-like soluble Ag. (2) Elucidate how early signaling events triggered by particulate Ag are transformed into immunogenic transcriptional programming of B cell fate through robust activation of NF-kB but not NFAT pathways. We will take a genetic approach to manipulate the second messenger diacylglycerol (DAG) which we hypothesize toggles between these immunogenic and tolerogenic B cell transcriptional responses. We will test this in human B cells. We will pursue a genomic strategy to survey the epigenetic landscape of B cells in order to define the transcriptional architecture that translates pattern of Ag display into B cell fate. (3) Systematically map the lower boundary of Ag affinity, density, and particle dose, and test the biophysical properties (particle size, membrane fluidity, linker length) required to activate B cells, including anergic self- reactive cells. We will test the hypothesis that these thresholds are controlled by Lyn-dependent inhibitory signaling pathways.

NINDS - National Institute of Neurological Disorders and Stroke

SUMMARY Diffuse dissemination of tumor cells into the brain is one of the key problems impacting optimal treatment of gliomas. We hypothesize that distinct types of tumor cells harbor characteristic diffusion patterns. Specifically, we suspect that NPC-like cells predominate in the cortical layers and interact with the laminar extension of neuronal cells in the cortex, while OPC-like cells dominate subcortically and associate with axons and APC-like cells associate with vascular and immune cells. In order to provide four-dimensional reconstructions of tumor development and test our hypotheses, we will perform spatial transcriptomics on n = 254 image-mapped samples from n = 22 distinct tumors (aim 1). Tumor-microenvironment interactions will be evaluated separately for each patient and by comparing distinct locations across patients. Finally, we will develop an agent-based model using n = 179 samples from n = 20 individual with integrated imaging, DNA methylation and DNA sequencing information to reconstruct historical and forecast future tumor development in space and time (aim 2). The findings of these studies will allow for a high-resolution dissection of the identity and location of ancestral stem- like tumor cell populations, as well as the identification of sites of diffuse infiltration. A four-dimensional model of tumor cell dissemination will enable individualized local treatment planning and prognostication.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

ABSTRACT Islet transplantation is a promising treatment for type 1 diabetes but suffers from significant islet loss with the standard intraportal liver infusion, consequently requiring large numbers of costly islets, often multiple transplants, and suboptimal achievement of long-term insulin independence. This is because islet isolation protocols result in regression of islet-specific endothelial cells (ISECs), with the loss of the critical, supportive islet vascular niche resulting in islet death. Furthermore, strategies to achieve islet engraftment in an extrahepatic site have been stymied by poor vascularization and lack of knowledge of how β-cell interaction with ISECs contributes to β-cell homeostasis. The overall goal of this project is to engineer ISECs to uncover the cellular cross-talk between -cells and their specialized vascular niche, to ultimately augment transplanted islet engraftment in the subcutaneous space. Each organ is vascularized by unique, specialized endothelial cells (ECs) that provide a tissue-specific vascular niche that supplies angiocrine factors key in choreographing organ homeostasis and repair. Indeed, there is growing evidence that a functional and physical interplay exists between specialized ISECs and -cells. Employing single cell analyses, we obtained a molecular signature of ISECs, identifying the novel transcription factor NKX2-3. This proposal will explore if vascularization of islets with NKX2-3+ ECs will facilitate engraftment, function, and survival of subcutaneously transplanted islets. ISECs have the additional critical feature of modulating the expression and migration of immune mediators, with macrophages being the most abundant pancreatic immune cell. In turn, these macrophages supply growth and immunomodulatory factors to sustain the integrity of -cells. Therefore, we hypothesize that induction of NKX2-3 in ECs confers these cells with the specialized properties of ISECs which, by supplying defined angiocrine factors and proper polarization of pro-reparative macrophages, support islet function. Accordingly, we will test the hypothesis that NKX2-3 is necessary for the specification of ISECs, which have the capacity to support islets in vitro and in vivo, through the following aims: Aim 1: Assess the impact on islet function of selective and conditional loss of NKX2-3 in pancreatic ECs. Aim 2: Examine the efficacy of enforced NKX2-3 expression in human umbilical vein endothelial cells in augmenting durable subcutaneous engraftment of transplanted islets. Aim 3: Decipher the mechanism by which NKX2-3, through macrophage polarization, coordinates pro-regenerative and anti-fibrotic islet innate inflammatory responses within the pancreas. The proposed training will guide and enhance my development in core competencies, including immunology, bioinformatics, and stem cell-derived islets, that will enable me to transition to research independence as a surgeon-scientist dedicated to improving islet transplantation outcomes. Weill Cornell Medicine is an ideal environment to execute this training plan due to its outstanding physical resources and its robust intellectual community of researchers with strong records of mentorship of early-stage investigators.

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT Bacteria shield themselves from the exterior environment with a rigid cell wall. The major structural component of this exoskeleton is the mesh-like peptidoglycan (PG), a heteropolymer composed of glycan strands and crosslinked stem peptides. Glycan strand polymerization and transpeptidation are catalyzed by penicillin-binding proteins (PBPs). Organisms express multiple PBP isoforms with varied spatiotemporal activity. Transpeptidation is inhibited by the b-lactams, a family of covalent inhibitors that mimic the terminal dipeptide structure of the nascent PG monomer; PBP inhibition results in growth abnormalities and cell lysis. Despite the therapeutic successes of b-lactam antibiotics, the current antimicrobial resistance crisis underscores the importance of understanding of PBP activity and inhibition, and cell wall composition more broadly. The Carlson Group studies PBP activity with chemical probes; however, achieving isoform selectivity is difficult due to spatial conservation of the transpeptidase active site. Specifically, the field lacks a comprehensive description of how conserved motifs in this active site mediate substrate and inhibitor binding. There is also a lack of understanding of how changes in the PBP activity profile alter PG composition. While nonuniformity of PG composition has been demonstrated in the context of bacterial resistance and host immune response to infection, a lack of bioinformatic methods for the unbiased identification of PG fragments impedes analyses of cell wall digests using liquid chromatography coupled to mass spectrometry (LC-MS). To address these outstanding questions in PBP activity and cell wall maintenance, the proposed research will use an alanine scan to map and quantify the contribution of conserved active site motifs in PBP2x from the Gram-positive pathogen Streptococcus pneumoniae to native substrate processing and b-lactam inhibition. Following initial assessment with a commercially available probe, this approach will be extended to a chemically diverse suite of b-lactams in live cell, in vitro, and in silico experiments to clarify how the active site permits occupancy of multiple inhibitor classes. Additionally, this project will use activity-based protein profiling and LC- MS/MS analyses to investigate how conditions mimicking the acidic infection microenvironment perturb PBP activity and PG composition. This work will be coupled to experiments probing the effects of transpeptidase inhibition and PBP deletion on PG structural diversity. Bioinformatic analyses of LC-MS/MS data will serve as crucial validation of the application of -omics strategies to interrogate PG composition. Ultimately, these aims will provide insight into key mediators of cell wall synthesis and maintenance, inform understanding of how bacteria leverage cell wall perturbations as defense mechanisms to evade antimicrobial threats, and inspire future probe design. The training plan will facilitate instruction in chemical biology, computational biochemistry, and bioinformatic -omics analyses through education in the group of Erin Carlson, and through collaborations at the University of Minnesota.

NIGMS - National Institute of General Medical Sciences

Myosin-X (Myo10) is a molecular motor crucial for the formation and function of filopodia, finger-like protrusions cells use interact with their surroundings in processes such as brain development, blood vessel formation, and the spread of cancer cells. We have shown that Myo10 localizes to the tips of filopodia, increases the number and length of filopodia, and moves within filopodia in a process known as intrafilopodial motility. Our generation of Myo10 knock-out mice showed that loss of Myo10 causes developmental defects in brain, eye, and blood vessels, but is not essential for survival of adult mice. Myo10 promotes tumor growth and invasion in many cancers, including breast, lung, and melanoma. Myo10 also has important functions in cell division, where it is required for spindle orientation and for clustering the excess centrosomes that are a hallmark of cancer cells. Myo10’s important roles in biology, plus the need to understand the fundamental cell biology of filopodia, make it essential to investigate the molecular mechanisms of Myo10 and filopodial function at the cellular and organismal levels. To fill these knowledge gaps, we will address the following: -How does Myo10 promote filopodia and what are its molecular cargos? -What are the functions of headless Myo10, a form of Myo10 that lacks the motor domain and is expressed in brain and stem cells? -Purify filopodia and use modern proteomics approaches to identify and quantify the full set of their molecular components, including the filopodial cytoskeleton, tip, and plasma membrane. -What are Myo10’s organismal functions in epithelial tissues such as kidney where it localizes basolaterally and in eye where KO results in major developmental defects. Because filopodia are a major cellular organelle whose purification has not been reported, we will combine our recent progress purifying filopodia with quantitative proteomics to identify the molecular components of filopodia. We will also take advantage of the extensive set of tools and techniques we have established to investigate Myo10 and filopodia, including Myo10 floxed and knock-out mice, KO and stable cell lines, and deletion and point mutant constructs. Although the other members of the MyTH4-FERM family of myosins in vertebrates have important roles in human physiology and disease at the tips of other protrusions based on actin bundles like epithelial microvilli and inner ear stereocilia, Myo10 is the MyTH4-FERM myosin present in filopodia and most mammalian cells and tissues. This research will answer fundamental questions about Myo10 and filopodia as well as investigating Myo10 functions at the organismal level in health and disease.

NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases

Project Summary/Abstract Tissue restoration is essential to maintain skeletal muscles after injury, due to overuse, aging or disease. Repeated cycles of muscle damage and repair are associated with muscle stem cell (MuSC) dysfunction and impaired myogenesis. Telomeres protect and stability and telomeric proteins do not only the end of our chromosomes from deterioration but are main components of the stem cell progenitor cells `ignition' mechanism, which maintain tissue homeostasis and genome by repairing damage throughout life .Although the telomere protective machinery has been primarily established during carcinogenesis and aging; its importance during regeneration and particularly in muscle injuries, a tissue known for its high regenerative capacity and low propensity for carcinogenesis, is not well understood. We previously demonstrated that telomere attrition is a distinct feature of dystrophic MuSCs in both mice and patients, even at very young ages. More recently, we discovered that TRF2, a key telomere-capping protein, is dynamically regulated in skeletal muscles and has distinct functions, independent of its conventional telomeric role. We also developed genetic tools to define how this protein operates in uninjured, injured, and diseased skeletal muscles. The studies proposed here will determine the extent of previously unknown extra-telomeric functions of TRF2 in muscle stem cells (Aim 1), they will define its new role in regenerating myofibers upon acute and chronic injuries and will uncover new interacting proteins during this process (Aim 2). We expect that this project will fundamentally advance our understanding of the molecular mechanisms by which TRF2 maintains stem cell identity versus how it regulates reparative myogenesis and could effectively guide ways of promoting regeneration and function in healthy and diseased conditions.

NIH

Project Summary/Abstract Significance to VA During deployment to Operation Desert Storm as an Army Medical Officer the Pl of this project cared for many soldiers with severe diarrhea, later shown to be caused primarily by enterotoxigenic E. coli (ETEC)1. These infections remain a major cause of acute diarrheal illness worldwide, have been responsible for major outbreaks in the United States, and fuel the global spread of antibiotic resistance determinants. In addition, these pathogens are closely associated with long-term sequelae including malnutrition and wasting in young children, tropical sprue in adults, and Irritable Bowel Syndrome (IBS) in returning Veteran service members. Gaps addressed by these studies Our understanding of the molecular pathogenesis of gastrointestinal pathogens as well as the composition of the commensal microflora is exceedingly biased by models that fail to faithfully recapitulate key features of the human intestine, particularly the major immunoglobulin superfamily glycoproteins known as CEACAMs. The proposed studies seek to overcome these deficiencies using transgenic mice and human stem cell-derived gastrointestinal organoids that accurately reflect the molecular organization of human small intestine. Innovation and Impact: These studies center on the interaction of ETEC and other intestinal bacteria (including commensals) with Carcinoembryonic Antigen-related Cell Adhesion Molecules (CEACAMs), which we have recently shown in novel human intestinal organoid models and a transgenic mouse model to play essential roles in pathogen­ host interactions, as well as innate response to ETEC. While thousands of intestinal microbiome studies have been performed in conventional mice, they lack CEACAM genes normally expressed in the human gastrointestinal tract. We therefore anticipate that the proposed studies will significantly impact our understanding of intestinal bacteriology and approach to care. Specific Aims: 1. Define molecular interactions between ETEC, EV and CEACAMs. 2. Examine the interplay of CEACAMs, intestinal microbiota and ETEC 3. Examine the impact of ETEC pathogen-host interactions on gene expression. Methodology: Aim 1 we will use recombinant CEACAMs to investigate interactions between the bacteria and these receptors. In addition, we will map glycosylation sites on CEACAM6 before and after treatment with ETEC heat labile toxin by mass spectrometry, mutate the respective sites, and examine their impact as recombinant proteins and in transformed cells. Aim 2: Here we will examine the impact of CEACAM expression and the introduction of ETEC on defined microbiota in a gnotobiotic core facility by next generation metagenomic sequencing. Aim 3: To examine the impact of EV- interactions with ETEC we plan to perform RNA sequencing (RNAseq) of bacterial RNA following contact with CEACAM-laden extracellular vesicles (EV). In addition, we will explore the impact of heat-labile toxin on activation of gene expression pathways that lead to CEACAM upregulation by this toxin. Path to Translation/Implementation: Although basic in nature, we anticipate that these studies will provide a more detailed understanding of both host-pathogen interactions and the intestinal microbiota that can readily be applied to improving preclinical testing of orally delivered drugs, vaccines, and other therapeutics.

National Park Service

The Mosaics in Science (MIS) internships provide college students and recent graduates opportunities to work at National Park Service sites and units for the purpose of completing STEM (science, technology, engineering, and math) internship projects in NPS units across the country. The MIS Program provides young adults with structured, safe and challenging work and educational opportunities through employment projects that promote personal growth, the development of life skills, and an ethic of natural resource stewardship.

National Park Service

The purpose of the Mosaics in Science Internship Program is to link college students and recent graduates to National Park Service sites and units for the purpose of completing STEM (science, technology, engineering, and math) internships in National Park Service units across the country.

NINDS - National Institute of Neurological Disorders and Stroke

Abstract Brain organoids (BOs) derived from human stem cells bridge the gap between monolayer cell culture studies and animal models, which have well-documented limitations. Monolayer cell culture models fail to accurately replicate the 3D interconnectivity in the brain; animal models, while helpful, are limited due to interspecies differences, with most research focusing on rather phenotypical rather than mechanistic aspects. Concurrent with the advancement of BO models is the urgent need to develop 3D micro instrumentation supporting these organoids to investigate brain development and disease in their accurate physiological environment. Conventional microelectrode arrays (MEAs) used for neuronal cell culture studies are planar, which limits recording access to a small fraction of cells on the bottom side of the organoid. Also, conventional microfluidics is inherently planar, and while recent advances in 3D MEAs and 3D microfluidics have enabled electrical and chemical interrogation in 3D, combining both features with tunability and precision to allow independent and simultaneous control is challenging. Recently, we reported new 3D micro instrumentation in the form of 3D shell MEAs and demonstrated its applicability for electrical recording from BOs. They feature lithographically patterned and chip-integrated electrodes and self-folding polymer shells that can be triggered to wrap around BOs to measure electrical activity from the entire organoid surface. The 3D MEA shell system is modeled on and resembles a miniaturized electroencephalography (EEG) cap; the process used to make them is size-scalable, chip-integrated, and mass- producible. In the research, we aim to develop and validate 3D Micro Electrode Fluidic Array (MEFA) shells with multi-modal electrical recording and biochemical control capabilities, offering high spatiotemporal resolution, tunability, and scalability. Since 3D spatiotemporal patterns of neurochemicals play a critical role in molecular and cellular events of neural development and disease, we propose to apply and validate the MEFA shells in two studies that mimic neurodevelopment and monitor the spatiotemporal effects in neurological disorders and their treatments in vitro. We anticipate that the proposed 3D MEFAs would revolutionize brain sciences by permitting real-time, in-situ studies of electrical and chemical stimulation and interrogation of BOs in a high- throughput manner. The proposed 3D scalable, reproducible, and tunable 3D micro instrumentation for BOs has broad relevance to understanding brain development in utero and the development of anatomically accurate drug and toxicity screening platforms for brain sciences and neurological disorders.

NINDS - National Institute of Neurological Disorders and Stroke

PROJECT SUMMARY Animals depend critically on their capacity to choose the appropriate time to act. In the absence of explicit cues, these decisions are thought to depend on internal deliberation that dictates action timing to maximize outcomes. A broad range of previous observations suggest that internally driven timing decisions involve a distributed network of brain regions. However, it remains unclear how these regions interact during decision-making; mechanistic understanding is very limited and hypothesized interactions between brain regions remain untested. This critical knowledge gap stems from two main factors. First, the absence of explicit cues makes decision timing unpredictable, which historically has presented problems for experimental design. Second, previous methods for measuring and perturbing neural activity, and for quantifying the dependence relations between neural activity patterns, have been ill-suited for probing interactions between brain areas on the relevant timescales. To overcome these barriers, our collaboration combines a novel behavioral paradigm, multi-region spike- resolution neural recording, rapid neural activity perturbation, and a range of model-based computational approaches. In recent work, our analysis of activity on individual decision trials has demonstrated the prominent involvement of a deterministic process, in contrast to recent models that emphasize stochasticity. We have also developed an approach for analyzing multi-region recordings that has revealed a modular structure in the influence of several frontal cortical regions on the striatum, an influence thought to be central to timing decisions. Our preliminary results for this proposal point to a revised decision model that involves an urgency-like signal and a source of unpredictability distinct from that of prevailing models. We have also begun to examine interactions between prefrontal and somatomotor circuits that are also thought to be central to timing decisions. Here we have found evidence of an interaction mediated primarily by corticocortical connections, and one that has a modular structure. Our proposed work would build on these results to test our new model and identify its neural substrates (Aim 1), and test existing ideas about prefrontal-somatomotor interactions (Aim 2). Here we will use multi-region Neuropixels recordings, and an approach we have recently demonstrated for fast optogenetic silencing during internally driven timing decisions. We will compare our new model to others using rigorous statistical methods for model selection. We will identify neural substrates by analyzing best-fit models and perturbation results. We will also continue to develop our new methods for quantifying interregional interactions from activity recordings. Collectively, our work will quantify relevant interactions between brain regions that could not be resolved with previous approaches, leading to improved models. This will provide a new foundation for understanding the neural mechanisms of a basic aspect of natural behavior with relevance to cognition.

NIGMS - National Institute of General Medical Sciences

Project summary Understanding the dynamic change of cell-type composition, functional evolution, migration, and interaction of single cells within complex tissue or in vivo environments is essential for advancing our knowledge of developmental, pathological, and therapeutic processes. Yet current single-cell analytical methods such as flow cytometry, histological staining, sequencing, and mass cytometry are inherently destructive and provide only static views of dynamic cellular processes. While intravital microscopy with multiphoton technology enables nondestructive real-time imaging of single-cell behavior in three- dimension (3D) tissue environment, its multiplexing capacity is constrained by reliance on a narrow range of spectrally distinct colors. As a result, we remain unable to continuously track live cells and their functional evolution in physiologically relevant environments. My research program addresses this critical gap by developing Spatiotemporal Multiplexed Antigen Revealing Technology (SMART), an innovative platform for multiplexed, longitudinal imaging of live cells. SMART enables repeated cycles of labeling and erasing of fluorescent signals on cell surface, allowing continuous tracking of dozens of extracellular markers on the same cells over time. By reconstructing these signals across cycles, SMART provides a dynamic view of cell phenotypes, migration, differentiation, and communication that current methods cannot achieve. Over the next five years, my laboratory will develop and establish SMART as a versatile and reliable tool through applications in PBMCs (peripheral blood mononuclear cells) phenotyping, immune cell migration and function, stem cell differentiation, and neuron–astrocyte interactions. These studies will demonstrate SMART’s ability to uncover how cellular states evolve and how microenvironmental interactions shape biological outcomes. Looking ahead, my long-term vision is to extend SMART into living organisms, enabling noninvasive, real-time, multiplexed imaging of cellular dynamics in vivo. This advance would transform our ability to study immune responses, stem cell fate, and neural development directly in their native environments, providing insights that cannot be obtained with current technology. Ultimately, SMART has the potential to redefine how biomedical research observes and understands cellular behavior across diverse biological systems.

NIGMS - National Institute of General Medical Sciences

ABSTRACT / SUMMARY Reactive oxygen species (ROS) and regulation of redox pathways are critical to human health and disease, as they influence cellular metabolism, signaling, and stress responses. Disruptions in redox homeostasis contribute to the pathophysiology of numerous disorders, including neurodegenerative diseases, muscular degeneration, and drug-induced cardiotoxicity. However, the tools for monitoring redox dynamics in living human cells remain limited in dimensionality, sensitivity, and applicability to disease-relevant models. To overcome these challenges, my research program aims to develop a next-generation, multiplexed optical platform for quantitative redox phenotyping and apply it to disease modeling and drug screening in human induced pluripotent stem cell (iPSC)- derived systems. Over the past five years, my lab has engineered two advanced genetically encoded hydrogen peroxide (H₂O₂) sensors, oROS-G and oROS-HT, exhibiting improved dynamic range, kinetics, and spectral flexibility. We established a high-throughput optical screening platform and integrated machine learning approaches to accelerate protein sensor engineering. These sensors have been applied in diverse host systems, including iPSC-derived neurons and cardiomyocytes, and have revealed new aspects of redox signaling in cell health. Building on this foundation, our future research will continue along three complementary directions. First, we will complete the development of a fully multiplexed, intensity-based TreDox sensor suite to simultaneously monitor oxidative pressure and antioxidant capacity with single-cell resolution in real time. Second, we will engineer lifetime-resolved redox biosensors and use fluorescence lifetime imaging microscopy (FLIM) to enable robust, expression-independent quantification of intracellular redox states. Third, using single-cell optical phenotyping, we will apply these tools to profile redox imbalances and early cytotoxicity signals in human iPSC- derived cardiomyocytes, neurons, and skeletal muscle cells. We aim to detect subtle cellular imbalances in redox pathways that precede cellular dysfunction and are often missed by traditional high throughput assays. This research program will fill critical gaps in our ability to study redox biology in human-derived host systems by integrating state-of-the-art protein engineering, advanced imaging, and human stem cell models. The tools and knowledge generated will improve our understanding of redox-linked disease mechanisms, enhance the predictive power of preclinical drug testing, and establish a flexible, generalizable platform for functional phenotyping at single-cell resolution.

NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development

Project Summary Pelvic floor disorders (PFDs) are common conditions that affect -25% of U.S. women. PFDs are morbid, with more than 50% of afflicted patients rating them as "worse than death·. As vaginal delivery is the greatest epidemiologic risk factor for PFDs-likely due to the pelvic floor muscle (PFM) dysfunction it often incites greater understanding of vaginal delivery biomechanics and birth injury is needed. But in order to accurately study the mechanical behavior of the PFMs during childbirth, their structure, function, and integrity just before childbirth must be known. Acquiring this knowledge is not trivial given the degree of pregnancy-induced remodeling that soft tissues undergo during gestation. Thus, this study aims to implement multiscale experimental and computational methods to characterize and simulate pregnancy-induced remodeling of PFMs. Phase 1 (K99) is the experimental arm of this proposal. In Alm 1 cell culture of primary 1) skeletal muscle stem cells and 2) fibro-adipogenic progenitors isolated from female rat PFMs will be used to determine the impact of sex hormones (e.g., estrogen) and mechanical stretch on resulting 1) myotube growth and 2) collagen secretion by fibroblasts, respectively. After the cultured cells have differentiated, myotube size, fusion index, and the amount of collagen secreted (quantified as a percentage of the sampled area) will be quantified via bright field (myotubes) and fluorescence (fibroblasts) microscopy. These will serve as proxies for muscle fiber growth and collagen deposition in vivo, allowing for the determination of the effect of sex hormones and mechanical stretch on the contractile and extracellular matrix (ECM) components of the PFMs. Meanwhile, Alm 2 will define changes in whole PFM active and passive mechanics across the nonpregnant-postpartum continuum. Whole PFMs will be harvested from rats at various stages throughout the pregnancy and postpartum, and then ex vivo active and passive mechanical testing will be performed. This will establish changes in force generating capacity (active properties) and load bearing capacity (passive properties) across the continuum, revealing how the function of both the contractile (active) and ECM (passive) components of PFMs are altered by pregnancy and childbirth. Phase 2 (ROO) is the computational arm of this proposal. Aim 3 will generate intracellular signaling network (cell level) and finite element (whole muscle level) models, calibrate and validate those models using literature and Phase 1 data, and then couple those models; resulting in a multiscale computational model of pregnancy-induced PFM remodeling. This coupled model will consider sex hormone levels, the degree of mechanical stretch acting on myofibers and the ECM, myofiber growth, and collagen deposition collectively while simulating their impact on whole PFM active and passive function. Together, these aims will characterize the multiscale (intracellular and whole muscle) mechanisms of pregnancy-induced PFM remodeling and identify the most influential sex hormones and mechanical properties driving these adaptations; thus, promoting translational studies evaluating the PFMs' ability to withstand vaginal birth and avoid injury.

U.S. Mission to Oman

The Public Diplomacy Section of U.S. Embassy Muscat announces an open competition to support projects that advance U.S. foreign policy priorities in Oman while strengthening the long-standing partnership between the United States and the Sultanate of Oman. This Annual Program Statement outlines strategic funding priorities, eligibility criteria, and application guidelines for grants ranging from $1,000 to $50,000, with project durations of up to 12 months. Successful proposals should clearly demonstrate how their projects support U.S. public diplomacy goals; showcase American excellence, expertise, innovation, and values, and strengthen the bilateral relationship. The goals of U.S. policy in the region are to: 1) secure opportunities that advance U.S. commercial and strategic interests; 2) promote trusted cooperation in emerging technologies, innovation, and space; and 3) deepen people-to-people ties that showcase American excellence. Applicants should clearly explain how their projects support U.S. public diplomacy goals, strengthen the U.S.-Oman partnership, and highlight American expertise, leadership, and innovation. Programs should include a clear U.S. element, such as engagement with U.S. experts, institutions, companies, universities, artists, athletes, alumni, or professional networks; the use of American models, standards, technologies, or best practices; or activities that increase understanding of the United States and its partnership with Oman. Program Description1. Project Background, Goals, and Objectives The Public Diplomacy Section of U.S. Embassy Muscat is pleased to invite applications for federal assistance funding opportunities, pending availability of funds, through its Public Diplomacy Small Grants Program. This Annual Program Statement outlines the Embassy s funding priorities, strategic themes, and procedures for submitting proposals. Applicants should carefully follow all instructions below. The Public Diplomacy Section seeks proposals for programs that advance U.S. foreign policy priorities in Oman while strengthening the long-standing partnership between the United States and Oman. Competitive proposals should clearly demonstrate how the proposed project makes the United States safer, stronger, or more prosperous; and showcases American excellence, expertise, innovation. Programs should include a clear U.S. element, such as engagement with U.S. experts, institutions, companies, universities, artists, athletes, alumni, or professional networks; the use of American models, standards, technologies, or best practices; or activities that increase understanding of the United States and its role as a trusted partner for Oman. 2. Program Objectives Applicants may submit proposals that address one of the program goals below. Proposals should focus on one or more of the priority outcomes, but applicants may also recommend their own objectives if they clearly align with U.S. Embassy Muscat priorities. Goal 1. Advancing U.S.-Oman Commercial Ties, and Shared Prosperity: This goal supports programs that make the United States more prosperous by expanding U.S.-Oman economic cooperation, strengthening commercial ties, and highlighting the value of trusted U.S. expertise, technology, standards, and business practices. Projects may support Omani entrepreneurs, students, business leaders, and institutions in sectors that advance shared economic priorities, including innovation, trade and investment, tourism, logistics, clean energy, creative industries, and other areas linked to Oman s economic diversification goals. Programs should demonstrate how engagement with U.S. experts, companies, universities, or professional networks can help Omani audiences develop practical skills, build market-oriented solutions, and identify opportunities for long-term U.S.-Oman commercial cooperation. Project Audience(s): Entrepreneurs, students, business professionals, chambers of commerce, academic institutions, economic organizations, youth, and relevant civil society partners. Priority Outcome(s): Applicants may focus on one or more of the outcomes listed below. Applicants are encouraged to propose additional objectives and innovative activities that address this priority program area. Increased awareness among Omani audiences of opportunities for U.S.-Oman trade, investment, entrepreneurship, and private-sector collaboration. Stronger connections between Omani entrepreneurs, students, or business leaders and U.S. experts, companies, universities, or professional networks. Greater understanding of American business practices, innovation models, market-based solutions, and trusted U.S. standards in sectors important to Oman s economic growth. New partnerships or project ideas that position the United States as a preferred partner for economic cooperation, entrepreneurship, and commercial innovation in Oman. Goal 2. Strengthening Sports Diplomacy, Youth Leadership, and Major-Event Expertise: This goal supports programs that use sports to advance U.S. public diplomacy goals, strengthen people-to-people ties, and share American excellence in sports management, coaching, athletic development, sports entrepreneurship, and major-event planning. As the United States prepares to host major global sporting events, including the Olympics, proposals may draw on U.S. experience in organizing, managing, and leveraging sports events to support youth development, community engagement, tourism, and economic opportunity. Projects should demonstrate how U.S. sports expertise can benefit Omani athletes, coaches, sports institutions, youth organizations, and communities while strengthening positive perceptions of the United States and expanding long-term U.S.-Oman cooperation in the sports sector. Project Audience(s): Youth, athletes, coaches, sports federations and clubs, schools, universities, sports entrepreneurs, community organizations, and relevant public or private-sector partners. Priority Outcome(s): Applicants may focus on one or more of the outcomes listed below. Applicants are encouraged to propose additional objectives and innovative activities that address this priority program area. Increased exchange of U.S. and Omani expertise in sports management, coaching, leadership, athletic development, and major-event planning. Expanded professional connections between Omani sports institutions, coaches, athletes, or youth organizations and U.S. sports experts or institutions. Greater understanding of how sports diplomacy can support entrepreneurship, education, health, tourism, and community development. Increased recognition of the United States as a global leader in sports innovation, major-event management, and sports diplomacy. Goal 3. Showcasing American Excellence in Culture, Heritage, and Creative Industries: This goal supports programs that showcase American excellence, creativity, innovation, and cultural leadership while strengthening cultural understanding between the United States and Oman. Projects may connect American and Omani artists, cultural institutions, heritage professionals, designers, filmmakers, musicians, writers, museum professionals, and creative entrepreneurs. Programs may highlight the role of culture and heritage in strengthening national identity, mutual understanding, tourism, and economic opportunity. Projects may also showcase U.S. excellence in creative industries, including film, music, design, museums, digital storytelling, gaming, publishing, architecture, cultural entrepreneurship, and other creative sectors where the United States has global influence. Projects under this goal should support marking the 250th anniversary of the founding of the United States. Freedom 250 programs should highlight American history, constitutional traditions, innovation, entrepreneurship, creativity, civic ideals, and the people-to-people ties that connect the United States and Oman. Project Audience(s): Artists, cultural institutions, museums, heritage professionals, students, youth, creative entrepreneurs, educators, writers, filmmakers, designers, alumni, and the public. Priority Outcome(s): Applicants may focus on one or more of the outcomes listed below. Applicants are encouraged to propose additional objectives and innovative activities that address this priority program area. Increased collaboration between U.S. and Omani cultural, creative, or heritage professionals and institutions. Greater public understanding of the United States through American arts, culture, history, innovation, and creative industries. Strengthened skills among Omani artists, cultural professionals, or creative entrepreneurs through engagement with U.S. experts, institutions, or models. Programs that connect Omani heritage and American creative expertise through exhibitions, workshops, public programs, digital storytelling, or joint cultural initiatives. Freedom 250 programs that increase awareness of American history, constitutional freedoms, innovation, entrepreneurship, and the long-standing U.S.-Oman partnership. Goal 4. Advancing Emerging Technologies, Space Cooperation, and Innovation: This goal supports programs that make the United States safer, stronger, and more prosperous by expanding U.S.-Oman cooperation in emerging technologies, space science, and innovation. Projects should showcase U.S. leadership in science, technology, and space while supporting Omani talent, institutional capacity, and innovation ecosystems in areas of shared strategic interest. Projects may focus on artificial intelligence, cybersecurity, data science, digital transformation, advanced manufacturing, biotechnology, clean technology, trusted digital infrastructure, satellite technology, Earth observation, STEM education, commercial space, or space entrepreneurship. Competitive proposals should include a clear U.S. connection, such as collaboration with U.S. universities, research institutions, technology companies, NASA-related educational resources, private-sector innovators, U.S. exchange alumni, or American experts. Programs should demonstrate how U.S. expertise, standards, and innovation models can help Omani students, researchers, entrepreneurs, educators, and professionals develop practical skills, build trusted partnerships, and contribute to long-term U.S.-Oman cooperation in technology and space. Project Audience(s): Students, youth, universities, researchers, entrepreneurs, technology professionals, STEM organizations, science communicators, educators, civil society organizations, and relevant public or private-sector partners. Priority Outcome(s): Applicants may focus on one or more of the outcomes listed below. Applicants are encouraged to propose additional objectives and innovative activities that address this priority program area. 1. Increased understanding among Omani audiences of U.S. leadership, standards, and best practices in emerging technologies, advanced technologies, space science, and innovation. 2. Stronger connections between Omani students, researchers, entrepreneurs, or professionals and U.S. technology, STEM, or space-related experts, institutions, and innovation networks. 3. Practical skills development in areas such as artificial intelligence, cybersecurity, data analysis, digital entrepreneurship, technology governance, STEM education, satellite technology, or space entrepreneurship, utilizing American platforms and providers. 4. Greater awareness of trusted, responsible, and secure U.S. technology solutions that support innovation, economic growth, institutional resilience, and shared security. 5. Programs that encourage U.S.-Oman collaboration in space education, Earth observation, climate and environmental monitoring, commercial space, science communication, or related fields.

NIAID - National Institute of Allergy and Infectious Diseases

Abstract Support is requested for a Keystone Symposia conference entitled “Myeloid Cells: Functional Heterogeneity with Therapeutic Promise,” organized by Drs. Charlotte L. Scott, Shalin H. Naik and Thomas Fabre, with scientific programming input from Keystone Symposia. The meeting will take place February 23–26, 2026 at the Keystone Resort in Keystone, Colorado, USA. Myeloid cells play crucial roles in the innate immune system, responding to infections and maintaining tissue homeostasis. Despite their significant therapeutic promise, the potential of myeloid cells is yet to be fully realized. This Keystone Symposia meeting aims to bring together key leaders in academia and industry to discuss recent insights regarding myeloid cell functional heterogeneity and how to target these cells for therapeutic interventions. This conference will highlight recent advances in our understanding of the role of myeloid cells in different disease settings, including cancer, infection and other immune-mediated disorders, which will enable new translational perspectives for understanding, treating, and preventing infectious and immunologic diseases. The meeting program will provide opportunities for attendees to gain a deeper understanding of unique and conserved myeloid cell populations across tissues and diseases and explore how these might be leveraged therapeutically. Through rigorous discussions, this meeting aims to outline key questions for future research that will harness the power of myeloid cells and showcase current and emerging technologies. A key feature of this meeting is that it will be co-located with another Keystone Symposia conference, “Hematopoiesis.” This partnership will provide valuable insights into the interconnected roles of hematopoietic stem cells and myeloid lineages in both health and disease. Inclusive poster sessions, panel discussions, shared meals and social activities will promote networking, encourage the sharing of cross-disciplinary insights and provide broader scientific perspectives important for future research collaborations towards the development of successful therapeutic strategies.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY Oxidative stress caused by dysregulated reactive oxygen species (ROS) plays a critical role in neurodegenerative diseases, cancer, and aging. Despite its importance, the boundary between ROS beneficial signaling and harmful oxidative stress remains poorly defined, in part due to limited tools for precise, real- time measurement of redox dynamics in live cells. Clarifying how cells respond to different ROS levels is essential to understanding redox regulation and developing strategies to mitigate oxidative damage. A better grasp of these mechanisms could impact diverse fields including neuroscience, cancer biology, and metabolic disease. The Usselman Lab at Florida Tech brings a unique combination of redox biology, hyperspectral imaging, and quantum sensing expertise. As a teaching-intensive institution, we also engage undergraduates directly in hands-on research, building the next generation of STEM leaders through immersive, high-impact training. We will engineer chemogenetic systems using D-amino acid oxidase (DAAO) to generate H₂O₂ with spatial and dose control in mammalian cells. Redox dynamics will be quantified using ratiometric biosensors, Seahorse metabolic assays, and a novel optically detected magnetic resonance microscopy (ODMRM) platform with nanodiamond quantum sensors. These tools will allow us to define oxidative thresholds, measure mitochondrial responses, and track real-time redox changes with subcellular resolution. This multidisciplinary approach offers a powerful framework for understanding redox adaptation and stress, with broad implications for human health.

NASA Langley Research Center

The National Aeronautics and Space Administration (NASA), Langley Research Center is releasing a Cooperative Agreement Notice (CAN) in support of the NASA Langley Office of Education entitled NASA Digital Learning Network (DLN). The CAN will be available upon its release by opening the NASA Research Opportunities homepage at http://nspires.nasaprs.com/external/ and then linking through the menu listings Solicitations to Open Solicitations. The overall goal of the proposed cooperative agreement is to manage and support the DLN infrastructure through staffing, operations, and content development/delivery of NASA-related distance learning experiences for students and teachers. NASA DLN objectives are to 1.) Plan, prepare, produce, deliver, and evaluate NASA-related STEM content modules for students and professional development experiences for educators. 2.) Establish and maintain collaborations with other distance learning professional organizations. 3.) Research and adopt new and emerging educational technologies that address NASA s eEducation goals. 4.) Provide distance learning services to NASA Education Projects associated with the three NASA Office of Education Divistions: Elementary-Secondary/eEducation, Higher Education, Informal Education. 5.) Promote the DLN at professional conferences, with the formal and informal education communities, and other appropriate partners in order to establish a broad level of engagement in NASA distance learning activities. Proposals from outside the United States will not be considered and all NASA education and training grant funds, as required by 14 C.F.R. Sections 1260.12 (c) (2) and 1260.12 (c) (3), support students and faculty that are U.S. citizens. An organization s relevant current and past performance will be one of the evaluation criteria for selection (all evaluation factors will be defined in the CAN). As defined in the NASA Grant and Cooperative Agreement Handbook recipients of NASA cooperative agreements may not be paid a profit. Electronically submitted Notices of Intent to propose are requested addressed to the contact identified below. Proposal due date and exact location of submissions will be identified in the CAN. Proposals received after that deadline will not be considered. For this notice, the provisions contained in the NASA Grant and Cooperative Agreement Handbook (NPR 5800.1) apply. Additional information on Cooperative Agreements with NASA may be found at: http://prod.nais.nasa.gov/portals/pl/index.html . Offerors are responsible for monitoring the NSPIRES site for the release of any amendments. Recipient eligibility will be based upon the requirements that are set forth in the CAN. Potential offerors are responsible for downloading their own copy of the solicitation and amendments (if any). All correspondence and or direct questions regarding this CAN shall be addressed to the primary point of contact in writing (e-mail) at Karen.C.Dempster@nasa.gov., NASA Langley Research Center, Mail Stop 126, Hampton, VA 23681.

NASA Headquarters

Awards will be made as grants, cooperative agreements, and inter- or intra-agency transfers depending on the nature of the proposing organization and/or project requirements. The period of performance for an award may be one to five years. Note that it is NASA policy that all investigations involving non-U.S. organizations will be conducted on the basis of no exchange of funds. An optional pre-proposal teleconference will be held on Feb 20, 2013 from 1:00 p.m. Eastern Time to 3:00 p.m. Eastern Time. Prospective proposers are requested to submit any questions in writing to CP4SMP@jpl.nasa.gov no later than 4 business days before the teleconference so that NASA will be able to cover as much information as possible at the teleconference. NASA plans to post written questions and answers and teleconference charts to the NSPIRES website. An opportunity to ask questions and solicit clarification will be provided in the teleconference. To dial into the teleconference, call 1-888-469-1385. The participant passcode is CP4SMP. For relay services for the hearing impaired, call 711 at least 30 minutes before the call is to begin. Only non-profits that are legally recognized by a federal, state or local authority, including all types of NASA Visitor Centers (e.g., private, state or federal entities) located in the United States or its Territories that provide science, technology, engineering and mathematics (STEM) education programming (such as but not limited to exhibits) are eligible to apply for this NASA Research Announcement (NRA). An eligible institution does not need to have the words museum, visitor center, science, or planetarium in its legal name. No later than the due date for proposals, proposers to this NRA are required to have: 1) a Data Universal Numbering System (DUNS) number, 2) a valid registration with the System for Award Management (SAM) [formerly known as the Central Contractor Registry (CCR)], 3) a valid Commercial And Government Entity (CAGE) Code, 4) a valid registration with NASA Solicitation and Proposal Integrated Review and Evaluation System (NSPIRES) (this also applies to any entities proposed for subawards or subcontracts.) Consult Section VII. Eligibility Requirements of this NRA for the complete detailed explanations and caveats related to institutional and all other eligibility criteria. Principal Investigator Requirement: Principal Investigators (PIs) must be the President, Vice President, Chief Executive Officer, Chief Financial Officer, Chairman of the Board, or similarly ranked executive (e.g., Planetarium Director, Director of Sponsored Research) from an eligible institution. Limit on Number of Proposals per Organization: Eligible organizations shall submit only ONE (1) proposal per DUNS number. If an eligible organization submits more than one proposal using the same DUNS number, then none of the proposals will be evaluated. The NASA Office of Education, in cooperation with NASA Headquarters' Offices of Communications and Chief Technologist, Mission Directorates (i.e., Aeronautics Research, Human Exploration and Operations, and Science), and Mission Support Directorate solicits proposals to support NASA-inspired space, science, technology, engineering, or mathematics (S-STEM) informal education projects, including exhibits and partnerships with K-12 schools or districts, to support inquiry-based education. This NRA or solicitation seeks projects featuring NASA-themed content in space exploration, aeronautics, space science, Earth science, or microgravity, or a combination of these topics (See Section III of this document) to support NASA education outcomes. Leadership of the proposed projects must reside at informal education institutions (IEI); partnership relationships are highly encouraged (See Appendix C for partnership discussion). Proposed projects should address NASA's most current Strategic Plan and propose efforts that are well-aligned with NASA and do not duplicate other federal investments. Proposals also should address substantiated (e.g., through an existing needs assessment or other evidence) national, regional or local educational needs or challenges and offer solutions with potential for significant impact. Examples of eligible projects include but are not limited to: exhibits (permanent, traveling, or virtual); STEM programming serving educators, students, youth, parents, and the general public; STEM programming for informal education providers and staff professional development (e.g., youth groups, out-of-school-time programs, youth group leaders, workshop or activity leaders, curriculum developers, docent managers, exhibit designers, library professionals, community education leaders, education and public outreach (EPO) professionals); informal learning research in STEM, informal education programs, data usage and analysis; curriculum support for informal science education, technology development, performing arts, or activities that are culturally focused on targeted populations, such as women and minorities. Grantee institutions have the responsibility for budgeting and documenting compliance with Code of Federal Regulations, 14 CFR 1230, commonly referred to as "the Common Rule for the Protection of Human Subjects." Research to develop NASA-themed exhibits, programs, curriculum products, etc., may involve full human subjects review through an Institutional Review Board or IRB or it may be exempt. An IRB also certifies when research is exempt. Every institution that intends to submit a proposal to this NRA, including the proposed prime award or any partner whether an informal education institution, other non-profit institutions, state and local Government agencies, and other organizations that will serve as subawardees or contractors, must be registered in NSPIRES. Electronic submission of proposals is required by the due date and must be submitted by an authorized official of the proposing organization. Such registration must identify the authorized organizational representative(s) who will submit the electronic proposal. All principal investigators and other participants (e.g. co-investigators) must be registered in NSPIRES regardless of submission system. Potential proposers and proposing organizations are urged to access the system(s) well in advance of the proposal due date(s) of interest to familiarize themselves with its structure and enter the requested information. Electronic proposals may be submitted via the NASA proposal data system NSPIRES or via Grants.gov. Organizations that intend to submit proposals via Grants.gov must be registered 1-- with Grants.gov and 2--with NSPIRES. Additional programmatic information for this NRA may develop before the proposal due date. If so, such information will be added as a Frequently Asked Question or FAQ or formal amendment to this NRA and posted on http://nspires.nasaprs.com . It is the proposer's responsibility to regularly check NSPIRES for updates to this NRA. When the CP4SMP+ portal page on NSPIRES is updated a notice will be added to the NASA Education Express weekly news service. To subscribe to NASA Express, go to http://www.nasa.gov/education/express .

National 4-H Council

Funds 4-H youth development programs including STEM, healthy living, and agriculture.

Department of Defense

National Defense Education Program (NDEP) Science, Technology, Engineering, and Mathematics (STEM) Consortia Request for Information (RFI) for the Office of the Under Secretary of Defense (Research & Engineering)

NGCP

Supports collaborative STEM programs for girls and women.

National Grid Foundation

Supports energy affordability, workforce development, STEM education, and environmental sustainability in National Grid service areas.

NASA Headquarters

OPPORTUNITY FOR THE USE OF THE INTERNATIONAL SPACE STATION BY DOMESTIC ENTITIES OTHER THAN U.S. FEDERAL GOVERNMENT AGENCIES 1.0 INTRODUCTION AND BACKGROUND The National Aeronautics and Space Administration (NASA) is operating a share of the United States accommodations on the International Space Station (ISS) as a national laboratory in accordance with Section 507 of the NASA Authorization Act of 2005 (P.L. 109-155) and to seek to increase the utilization of the ISS by other federal entities and the private sector. To facilitate and increase such utilization of the ISS, NASA is providing access to the ISS for the conduct of basic and applied research, technology development and industrial processing (collectively, R&D) to U.S. federal, state and local government entities, and to U.S. private entities (including, but not limited to, commercial firms, non-profit entities, and academic institutions) as part of the national laboratory. In preparation for the ISS post-assembly phase and during the post-assembly complete phase, NASA is seeking proposals from domestic entities other than U.S. federal government agencies for the conduct of R&D activities on the ISS as a national laboratory. NASA anticipates using its authority to enter into Space Act Agreements to support national laboratory activities, including providing necessary access to NASA facilities, personnel and technical information, however, there will be no provision of funds in connection with this opportunity. Respondents will be responsible for financing their own activities. Participation in this National Lab Opportunity will be contingent upon selection by NASA and negotiation of an appropriate Agreement between NASA and the proposer. Proposed activities should involve R&D, including, but not limited to, life sciences, sensors, communication equipment, engineering testbeds, spacecraft design and testing, or education and should demonstrate potential benefit to the public, such as development of future products and services contributing to U.S. industrial capacity and economic growth or improving STEM education. This opportunity is not exclusive; NASA, at its discretion, may negotiate with other parties for access to ISS under this opportunity. Response Date: This announcement is open through December 31, 2014. NASA will engage in ongoing review of proposals as received prior to the Response Date of December 31, 2014. NASA reserves the right to amend or withdraw this Announcement at any time prior to the Response Date. NASA will not issue paper copies of this Announcement. NASA reserves the right to select for Space Act Agreement negotiations all, some, or none of the proposals submitted in response to this Announcement. NASA provides no funding for reimbursement of proposal development costs. Material submitted in response to this Announcement will not be returned. It is the policy of NASA to safeguard all proposals as confidential and privileged information, as provided by law. NASA will not, without permission of the proposers, use the proposal contents for other than evaluation purposes. It is not NASA's intent to publicly disclose proprietary information obtained during this solicitation. To the full extent that it is protected pursuant to the Freedom of Information Act and other laws and regulations, information identified by a respondent as "Proprietary or Confidential" will be kept confidential. NASA may use contractor support personnel to assist in providing expertise regarding proposals. Any support contractor involved in the evaluation process shall be free of conflicts of interest, will be bound by appropriate non-disclosure agreements to protect proprietary and competition sensitive information. By submitting a proposal under this Announcement, the proposer is deemed to have consented to release of data in its proposal to NASA contractors supporting evaluation of proposals. 2.0 GENERAL INFORMATION Agency Name: NASA (National Aeronautics and Space Administration) Opportunity Title: Opportunity for the use of the International Space Station by Domestic Entities Other than U.S. Federal Government Agencies Response Date: Electronic Proposals must be received by December 31, 2014 at 4:30 P.M. EST via email to jason.c.crusan@nasa.gov. Proposals may be submitted at any time before the response date. Points of Contact: If you have any questions concerning this opportunity please contact: Marybeth Edeen Manager, ISS National Lab Office Telephone: 281-483-9122 Fax: 281-244-8292 Email: marybeth.a.edeen@nasa.gov Jason Crusan SOMD Agreement Manager 202-358-0635 202-358-3530 jason.crusan@nasa.gov Instrument Type(s): It is anticipated that awards under this Opportunity will be in the form of Space Act Agreements, executed under the authority of 42 U.S.C. 2473(c)(5). Selection Recommendation Committee: Government personnel from NASA, other Federal agencies, and NASA contractors may participate in the evaluation of proposals. All contractor personnel participating in the evaluation will be bound by conflict of interest provisions and appropriate non-disclosure requirements to protect proprietary information. Selection Notification Date: Selection for negotiations is anticipated to be within 60 days of receiving a proposal. Submission Instructions: All Proposals under this Announcement must be emailed to jason.c.crusan@nasa.gov. Paper submissions will not be reviewed. Proposals may be submitted at any time before the Response Date. You are encouraged to submit as early as practicable prior to the Response Date. Proposals received by the Government after the Response Date will not be accepted. If a proposer is concerned about information security during transmission NASA has the ability to accept secure transmission. Contact the Point of Contact for secure transmission requirements. Files can be submitted in MS Word, PDF, or RTF. 3.0 ELIGIBILITY INFORMATION All categories of domestic entities other than U.S. federal government agencies are eligible to submit proposals in response to this Announcement. NASA will not consider proposals which do not include a domestic entity as the lead proposer. 4.0 PROPOSAL EVALUATION AND SELECTION 4.1 Evaluation and Selection Process All proposals will be initially screened to determine their compliance to the eligibility (section 3.0) and proposal instructions (section 5.0) of this Announcement. Proposals that do not comply may be declared noncompliant and rejected without further review. A submission compliance checklist is provided in section 5.0. This checklist provides proposers a list of the items that NASA will check for compliance before releasing a proposal for evaluation. Proposals deemed in compliance with this Announcement will be assessed against the evaluation criteria outlined in Section 4.2 by the Selection Recommendation Committee. Proposed collaborators should be aware that during the evaluation and selection process, NASA may request clarification of a specific point or points in a proposal. Such a request and the proposed collaborator's response shall be in writing. NASA reserves the right to suggest collaboration between proposers where it will enhance the effort, in which case proposers will be given the opportunity to accept or decline participation with other proposers prior to selection. The Selection Recommendation Committee members will conduct independent assessments of the proposals according to evaluation criteria outlined in Section 4.2. 4.2 Evaluation Criteria The evaluation factors below are of equal weighting during evaluation. Factor 1: Approach to Proposed Effort: The overall merit, rationale, feasibility, and suitability of the proposed effort or concept and its relevance to R&D that access to the ISS provides. Highest priority will be placed on an approach or concept that will create substantial increases in the current state-of-the-art. Describe how the proposer proposes to receive resulting data and/or samples from orbit. Factor 2: Level of Benefit to the Public: The proposed effort or concept's anticipated benefit to the public, in terms such as development of future products and services, and contribution to U.S. industrial capacity and/or economic growth. Factor 3: Level of Financial Commitment and Business Plan: The description of the level of financial commitments supporting the proposed efforts, including any third party financing required. Include a brief business plan for the proposed efforts or describe how the proposed efforts contribute to existing business plans. Identify the non-U.S. Government market potential for the R&D efforts. The proposed space activity is essential to product research, development, or processing, and is targeted to an addressable market. A roadmap exists; it includes the essential activities to bring the product to market beyond the development space activities. In addition, describe all cargo to be transported between Earth and the ISS that your proposed efforts require and how your business plan addresses meeting those requirements including any sample return and disposition of the on-orbit equipment/payloads. In addition, NASA reserves the right to assess information outside the proposal as it relates to the factors listed above. 4.3 Selection Factors As described in Section 4.1, the results of the proposal evaluations based on the criteria above and the subsequent Selection Recommendation Committee deliberations will be considered in the selection process. The Selection Recommendation Committee may take into account a variety of programmatic factors in deciding whether or not to select any proposals, including, but not limited to, available on-orbit resources, and compatibility to the ISS. The Selection Authority shall be the Associate Administrator for Space Operations. The Selection Authority will make the final selection of those approved for this opportunity after the completion of negotiations, depending on the outcome of the negotiations. 4.4 Selection Notification NASA will notify all proposed collaborators of the results of the evaluation and selection process. Selection does not guarantee a launch opportunity. Selection does guarantee NASA will provide the on orbit resources and trained crew to perform the experiment once it is on board. After the completion of the evaluation and selection process, NASA will begin negotiations with the selected proposer(s). The purpose of the negotiations is to define the terms and conditions of the Agreement supporting the participation of the proposers and to align the selected proposals with the anticipated on-orbit resource availability. All work will commence after the parties execute the Space Act Agreement. 5.0 PROPOSAL INSTRUCTIONS Proposals must comply with the following requirements. Page Limitations Proposal Section - Total Pages Proposal Cover Page - 1 Proposal Title Page - 1 Points of Contact - 1 Proposal Abstract - 750 words Proposal Detail - 10 Appendix Resumes - No Page Limit Additional Documentation - No Page Limit Pages in excess of the page limitations for each section will not be evaluated. A page is defined as one (1) sheet 8 x 11 inches using a minimum of 12-point font size for text and 8-point for graphs. There is no limit on appendix documentation. The intent is to allow proposals to include current documentation in its current format without having to alter any documents. The proposal must include the following sections, in this order: Proposal Cover Page: Solicited Proposal Application - Title of Announcement and Proposal Contact Information. An optional graphic image may be included. Proposal Title Page, with Notice of Restriction on Use and Disclosure of Proposal Information, if any. Points of Contact: List contact information for all Points of Contact including a Technical Point of Contact. Provide: a. Name b. Title c. Address d. Phone and Fax e. Email Proposal Abstract: Executive summary describing the prominent and distinguishing features of the proposal. Proposal Detail: The proposal shall contain sufficient information to enable reviewers to make informed judgments to assess the three criteria of the proposed effort. Proposal Appendix: * Resumes o Resumes may be included for key personnel. In general, resumes should be limited to no more than 1-2 pages each. * Additional documentation Include any documentation in the appendix that validates or supports the proposal Compliance checklist and required documents o The proposer is a domestic entity other than U.S. federal government agency o Proposal includes demonstration of the overall merit, rationale, feasibility, and suitability that access to the ISS provides o Proposal includes a description of the level of benefit to the public o Proposal includes a description of the level of financial commitment and business plan o Proposal includes a schedule for remaining development required before flight o Proposal includes a management/ project plan for remaining development o Proposal includes funding commitment letters demonstrating sufficient financial support for remaining development or financial milestones required to complete development