Grants

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Mapping the Complex Processes and Outcomes of Care Planning

NINR - National Institute of Nursing Research

Advance care planning (ACP) supports patients in identifying and communicating their preferences for medical care and is a key component of individualized care. The Patient Self Determination Act of 1990 narrowly defined ACP as documentation of preferences for end-of-life procedures (e.g., resuscitation), resulting in a focus on advance directive completion. Since then, ACP has evolved to include a focus on preparing patients and caregivers for communication and decision-making across the illness trajectory, which is better conceptualized as “Care Planning” (CP) because the process includes both advance and in-the-moment decisions over the life course. While health systems have invested in CP as a requisite component of individualized care and it is reimbursed by the Centers for Medicare and Medicaid Services, wide heterogeneity of CP implementation and measurement remain, and the perspectives and needs of patients, caregivers, and interdisciplinary experts (e.g., nurses, attorneys, chaplains, etc.,) have not been considered. Unprecedented basic science (NIH Stage Model, Stage 0) is required to map the complexity of the entire CP process. Implementation science and human factors engineering offer a path towards clarity. This proposal advances the field of CP and implementation science by leveraging interdisciplinary expert, patient, and caregiver perspectives and human factors engineering methods to map implementation processes of CP and to identify clinically relevant CP outcomes across clinical and community settings and illness trajectories. We will apply the well-validated Consolidated Framework for Implementation Research (CFIR) model to illuminate CP’s complexity. CFIR domains include CP innovation characteristics (e.g., discussions) that operate in an inner setting (e.g., inpatient, outpatient, nursing home, hospice) and outer setting (e.g., policy) centered around subject matter experts (e.g., patients, caregivers, healthcare professionals, community leaders, legal/policy experts) involving a range of implementation components (e.g., initiating, facilitating, documenting, storing, accessing, updating CP wishes). This complexity is amplified by patients’ illness trajectories and setting. Our study aims are to: 1) Define processes of CP for varying settings (community, outpatient, acute care, long-term care, hospice), illness trajectories (healthy/chronic illness, serious illness, end-of-life) and healthcare access by creating CP Workflow Archetypes; and 2) Identify clinically relevant outcomes for each component of the CP Workflow Archetypes. Using CFIR and human factors engineering, we will map essential implementation factors of CP through focus groups and interviews and use Delphi methods to identify important implementation outcomes. Our long-term goal is to set the direction for future CP policy, research, and implementation.

Up to $836K

2029-03-31

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Mapping the determinants of bedaquiline resistance in Mycobacterium tuberculosis

NIAID - National Institute of Allergy and Infectious Diseases

SUMMARY Bedaquiline (BDQ) is recently developed antibiotic that is used to treat extensively drug-resistant Mycobacterium tuberculosis (Mtb). The vast majority of BDQ resistance mutations are in the non-essential mmpR gene (Rv0678). Resistance to many anti-Mtb drugs can be inferred directly from gene sequences; however, this is not the case for BDQ resistance, largely because there are insufficient data linking specific mmpR mutations with resistance. In this proposal, we will use saturating mutagenesis to create a comprehensive database of mmpR loss-of-function mutations that lead to BDQ resistance. This database can be used together with whole-genome or amplicon sequencing approaches to rapidly diagnose resistance in clinical isolates. In parallel, we will test the ability of this database to predict BDQ resistance in clinical isolates of Mtb. Our long-term goal is to incorporate BDQ resistance profiling into existing genetic analysis pipelines.

Up to $404K

2028-03-31

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Mapping the Epigenomic and Spatial Transcriptomic Landscape in Parkinson's Disease

NINDS - National Institute of Neurological Disorders and Stroke

Project Summary Alzheimer’s disease (AD) and Alzheimer’s disease-related dementia (ADRD) and Parkinson’s disease (PD) are chronic neurodegenerative disorders characterized clinically by cognitive impairment and neuropathologically by abnormal protein accumulations (Aβ and α-Synuclein). Recent advances in understanding transcriptomic changes in AD and PD have focused on specific cell subpopulations and brain regions, such as microglia in the parahippocampal gyrus in AD and dopaminergic neurons in the substantia nigra in PD. Although significant, this narrow focus has diverted attention on other cell types and brain regions implicated in those diseases. Recognizing this shortfall, our project broadens the scope of studied cell subpopulations and brain regions with a special emphasis on deciphering impaired cellular cross-talk, detecting perturbed spatial interactions with morphological markers, and identifying gene regulatory programs driving AD and PD progression. In our previous work, we have established two resources through single-nuclei profiling. The first is a cross-disorder atlas that includes data from the prefrontal cortex of 1,494 donors with seven major brain-related disorders, including AD, PD, and other dementia. The second is a PD-specific atlas derived from 100 PD donors, encompassing five different brain regions. Our current proposal aims to leverage data from both AD/ADRD and PD datasets to systematically describe the differences in the transcriptional landscape of those diseases and augment the PD-centric atlas by integrating epigenomics and spatial transcriptomics. In Aim 1, we will characterize shared and distinct transcriptional changes between AD, PD and related dementia and identify cell types with significant proportional shifts associated with the disease progression. For the prefrontal cortex, included in both previously generated resources, we will conduct detailed comparative analyses between those diseases with a special focus on the interplay between AD and PD neuropathology measured by the Braak scoring system, i.e. accumulation of neurofibrillary tangles and Lewy bodies. Aim 2 focuses on developing an atlas of brain regulome changes in PD, which will pinpoint altered epigenetic regions leading to disruptions in chromatin structure. Utilizing both epigenomics and transcriptomics data will help us uncover enhancer-driven gene regulatory networks and model how these networks shape the transcriptome during disease progression by manipulating key epigenome regulators and related TFs. By integrating epigenome data with genome-wide association studies on PD, we will identify cell subtypes with increased PD heritability and refine the mapping between risk loci and the causal genes. Aim 3 will utilize integrative spatial genomic assays to detect differential cell-to-cell interaction networks, pointing to the gain or loss of ligand-receptor relationships and spatial relationships with morphological markers. Collectively, these studies will enable us, at unprecedented resolution, to explore brain region- and cell-type-specific transcriptomics and epigenomics responses in PD and distinguish them from those employed in AD and ADRD.

Up to $670K

2030-12-31

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Mapping the Fascicular Anatomy of Human Sciatic Nerve to Inform Electrode Designs and Placement Locations to Improve Standing Neuroprostheses

NIH

1 Our ultimate objective is to help Veterans with spinal cord injuries (SCI) regain the ability to stand through 2 peripheral nerve stimulation (PNS), specifically targeting the sciatic nerve (SCN). Traditional standing 3 neuroprostheses aim to selectively activate nerves that control key muscles in the knee, hip, and trunk to 4 maintain standing. Independent activation of muscles in the lower limb with control algorithms paired with 5 sensory feedback further improves standing performance with such neuroprostheses. However, achieving 6 selective activation of the muscles innervated from the upper sciatic nerve has been historically proven to be 7 difficult. The neural fascicles that control multiple major muscle groups are all contained within the proximal SCN 8 (i.e., prior to their distal branching into discrete motor unit components). This makes it more difficult to individually 9 activate the hip extensor muscles, particularly the hamstrings, which are critical in positioning the mass of the 10 head, arms, trunk, and pelvis over the legs. To address this, our SPiRE award project has two main goals. First, 11 we plan to create a 3D model of the SCN fascicles, using microCT and histology techniques. Second, we will 12 characterize nerve and fiber morphology (using Histology) to inform electrode placement and design 13 approaches. This information will ultimately guide the design and surgical placement of new multi-contact nerve 14 cuff electrodes to improve the performance of standing neuroprostheses for SCI patients. During Aim 1, we will 15 develop a 3D model of the fascicles of the SCN, from sciatic notch to the distal branch points, using µCT 16 and histology. The spatial orientation between nerve fibers of the fascicles with respect to neural stimulation 17 electrode placement determines the functional performance of standing neuroprostheses. Hence the 18 development of a 3D model of SCN is crucial to computationally evaluate various electrode designs (electrode 19 geometry, placement, number of contacts and size of contacts) to ultimately achieve increased fiber recruitment, 20 and improved selectivity of fiber recruitment, of the hamstring muscles. During Aim 2, we will complete the 21 most comprehensive histological characterization of the proximal sciatic nerve performed to-date. We 22 will quantify the morphology of the SCN along the nerve at high-resolution. The output of this aim will be used to 23 a) inform the feasibility of invasive electrode approaches, b) validate our fascicle morphology findings from 24 microCT, and c) establish the parameters required to create accurate computational models in the future.

2027-12-31

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Mapping the humoral immune response to the surface glycoproteins of the mumps virus

NIAID - National Institute of Allergy and Infectious Diseases

Abstract Mumps virus is one component of the MMR vaccine, which has been successful in the global effort against measles, mumps and rubella. However, of the three viruses, protection against mumps is the least effective. Cycles of mumps virus outbreaks continue to occur, especially among young adults and even in the vaccinated. 10% of patients in a recent San Diego County outbreak were hospitalized. Breakthrough infections could be linked to sequence differences between the vaccine strain and the newly emerged mumps genotype G. Surprisingly, although we have had this vaccine since 1971, medical science still does not know what the human antibody response is against mumps virus, from either vaccination or natural infection. No human antibodies against mumps have been yet described, and no structures of any antibodies against mumps have yet been determined. Thus, we are lacking understanding of which antibodies and which epitope target sites on the surface proteins HN and F are most effective, and we are lacking the antibodies themselves which might be incorporated into post-exposure treatments. In this program, we will develop panels of human monoclonal antibodies against mumps HN and F from both vaccinated and convalescent individuals. Results obtained from this program will illuminate what humans target in their immune responses, and which target sites, or epitopes, lead to broadest viral genotype recognition, especially between vaccine-derived genotype A and currently circulating genotype G of the virus. The results of this program will also provide the essential mAbs themselves from which we may develop post-exposure treatments and guide development of boosters.

Up to $279K

2028-04-30

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Mapping the m3C epitranscriptome in cancer

NCI - National Cancer Institute

Mapping the m3C epitranscriptome in cancer Project Summary RNA modifications are critical regulators of gene expression, with over 170 types identified across RNA molecules. Among these, m6A, m5C, and m1A are quite extensively studied for their roles in mRNA transcription, stability, and translation. In contrast, 3-methylcytidine (m3C) has been predominantly associated with tRNA modification and function, and is required for normal mRNA translation. The potential role of m3C in mRNA remains poorly understood and controversial due to conflicting experimental evidence. Mass spectrometry has suggested the presence of m3C in poly(A)-enriched RNA, but transcriptome-wide studies using chemical cleavage and next-generation sequencing have yet to provide definitive confirmation. Current methods like HAC- seq, ARM-seq, and DM-tRNA-seq are effective for tRNA modifications but inadequate for low-abundance or sub- stoichiometric m3C in mRNA. To address these limitations, this proposal will establish a highly sensitive and precise method (HARP-seq) to map m3C modifications in mRNA at single-nucleotide resolution. By integrating advanced chemical labelling & enrichment strategie, high-throughput sequencing, and bioinformatics analysis, this research will comprehensively characterize the distribution of m3C in mRNA. We will apply the newly developed method to investigate m3C modifications in mRNA across various cancer cell lines, primary tumor samples, and matched normal tissues. These findings will not only resolve current controversies regarding m3C's presence in mRNA but may provide insights into cancer-associated m3C epitranscriptomic changes and advance our comprehension of epitranscriptomic contributions to oncogenesis.

Up to $168K

2028-04-30

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Mapping the Mechanome: A Systems-level Understanding of Mechanical Mediators and Pathways

NIGMS - National Institute of General Medical Sciences

ABSTRACT The central goal of this application is to harness cellular mechanobiology to achieve predictive control over cellular behaviors that are critical for physiological and disease contexts. A growing number of diseases are attributed to dysfunction in cellular mechanical regulation; mechanical and physical cues are now known to regulate cellular behaviors in diverse contexts from muscle regeneration to cancer progression to cellular reprogramming. Although specific mechanical signaling mediators and pathways have been well-studied at molecular and cellular scales, these mechanistic studies use a bottom-up approach that focuses on a single protein or pathway in a single cell type. However, cells integrate signals from various sources across timescales and length-scales to produce a coordinated response, which requires a top-down or systems-level understanding of the ‘mechanome’—the set of genes, proteins, and pathways that regulate cellular mechanotype—and represents a major gap in the field. If we had a systems-level understanding of the mechanome this would enable fundamental knowledge of cellular mechanobiology. Such knowledge of the mechanome would allow us to intervene and control the time-dependent trajectories of cells and is crucial for effective interventions for human health as well as engineering self-assembling cellular structures and tissues with spatio-temporal control. Building on my lab’s recent research achievements and new preliminary data, the Rowat lab will pursue two future lines of research: 1) To identify novel mediators of cell mechanical behaviors, we will take an unbiased approach using the high throughput cell filtration platform that my lab has developed to conduct a genome-wide pooled shRNA screen. Follow up studies will validate the top hits using complementary measurements of cell mechanics, force generation, and motility across cell types. We will further investigate mechanisms of how top candidates as well as the novel mechanical mediator, NUDT5, which we previously identified in an initial deformability screen, mediate the mechanical behaviors of fibroblasts and immune cells. 2) To define mediators of mechanical memory, we will engineer a small molecule screen to identify molecules that mediate cellular mechanical behaviors that persist over generations after mechanical priming, using cellular morphology as a readout for cells plated on a compliant substrate following culture on a stiff substrate. Follow up studies will define mechanisms of how the top candidate mediators control mechanical memory by quantifying effects on cell mechanical behaviors and subcellular phenotypes. Taken together, findings will provide a platform for generating unbiased, systems-level knowledge of the mechanome. Findings will also provide the foundation for an interactive, web-based mechanome atlas, a resource that will be accessible to broader research communities.

Up to $433K

2031-01-31

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Mapping The Molecular Architecture Of Biomolecular Condensates With Crosslinking Mass Spectrometry

NIGMS - National Institute of General Medical Sciences

Project Summary/Abstract Biomolecular condensates have become the subject of intense interest across the biological, biophysical, and biomedical communities because they represent an elegant form of higher-order organization that cells can use to create dynamic compartments; they also are connected to a wide range of diseases, particularly those related to ageing and neurodegeneration. However, we lack a detailed structural model for any natural biomolecular condensate. Mapping the architecture of these assemblies is challenging because they are heterogeneous, liquid-like, prominently feature intrinsically disordered regions (IDRs), and are exquisitely sensitive to their environment. Crosslinking mass spectrometry (XL-MS) is uniquely suited to map the architecture of biomolecular condensates because it can freeze structural information about proteins when they are in their native cellular context and is equally adept at probing folded and disordered regions. In vivo XL-MS has not yet been applied to map native condensates in situ. The investigator has a unique combination of technical expertise in XL-MS and background in protein folding and biophysics; hence, is particularly well suited to this task. This proposal consists of three broad thrusts. Firstly, we seek to advance tools and methodology to map condensate structure, by (i) expanding the capacity of existing methods to capture protein-RNA interactions through photo-crosslinking and (ii) developing computational workflows that combine artificial intelligence, crosslinking data (as experimental restraints), and molecular dynamics for integrative/hybrid modeling of large assemblies. The other two thrusts focus on two specific condensate systems, the Caulobacter crescentus PopZ granule and the mammalian nucleolus. PopZ forms a polar 150-nm microdomain that regulates cell division and physiological changes during Caulobacter's lifecycle. We aim to understand how this condensate's structural properties evolve over the course of cellular development, and hypothesize that structural models of this assembly will provide a molecular basis to the processes responsible for differentiating the cell's two poles. The nucleolus is a larger, more complex condensate responsible for ribosome biogenesis in eukaryotes. Whilst some proteins within it are well-understood, including the structured ribosome assembly factors and a few high-abundance scaffolding proteins, many of its proteins are quite disordered and poorly characterized. We will obtain high- coverage crosslinking maps of the nucleolus with a range of techniques that will additionally focus on rRNA- protein crosslinking. These experiments will also characterize interactions among ribosome assembly intermediates and the whole host of nucleolar proteins, thereby uncovering potentially new ribosome biogenesis factors and functional roles for IDRs. A further goal is to map contacts between scaffold proteins (fibrillarin and NPM1) to other nucleolar proteins to interrogate the role of heterotypic interactions in supporting the organelle's unique tripartite substructure. To summarize, the PI seeks to lead efforts to apply structural proteomics to build high-resolution models of native biomolecular condensates. The PI anticipates this will represent a third of his research program, with other complementary efforts on protein folding biophysics and aging/neurodegeneration.

Up to $415K

2031-02-28

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Mapping the mutational landscape of CD4bs broadly neutralizing HIV antibodies

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Broadly neutralizing antibodies (bnAbs) that target the CD4 binding site (CD4bs) on the HIV envelope glycoprotein (Env) are an attractive target for an HIV vaccine and antibody-based therapy for HIV protection. However, eliciting CD4bs bnAbs in a vaccine is challenging, and current CD4bs bnAbs are insufficient to provide long-term HIV suppression. This difficulty in CD4bs bnAb-mediated treatment stems from Env mutations near the CD4bs referred to as “loop D,” including the gain of a glycan at N276 that has yet to be dependably overcome in vaccine regimens. Although improvements in antibody isolation have provided mechanistic and evolutionary insight into some CD4bs bnAbs, it remains poorly understood how CD4bs bnAbs evolve breadth and potency from their naïve precursors, complicating attempts to elicit them via vaccination. To address this issue, high-throughput deep mutational scanning (DMS) techniques will be used to characterize the effect of all possible single-amino acid mutations at each position in the variable domains of the VRC01 and IOMA CD4bs bnAbs that represent two stereotyped mechanisms of Env CD4bs recognition. VRC01 and IOMA variant libraries will be expressed on the cell surface of yeast. Using this yeast-surface display (YSD) platform, both VRC01 and IOMA variant binding affinities will be measured against various Env proteins using fluorescence-activated cell sorting and high-throughput sequencing (FACS-seq), facilitating the measurement of the binding properties of these bnAb libraries in parallel. Aim 1 will determine the mutations in CD4bs bnAbs that enable HIV Env N276 glycan accommodation. DMS, YSD, and FACS-Seq will be performed on libraries of mature VRC01 and its naïve precursor to determine their binding affinities to two closely related donor-autologous Env proteins that contain and lack the N276 glycan. These experiments will reveal routes to overcome common barriers in CD4bs bnAb development and illuminate how the next generation of immunogens will better elicit broad and potent bnAbs. Aim 2 will map the mutational landscape that confers CD4bs bnAbs breadth and potency. DMS, YSD, and FACS-seq will be performed on mature VRC01 and IOMA to measure the impact of all single mutations on binding to a previously established panel of 12 heterologous Env strains that comprise a reference of global Env diversity. These results will illustrate how mutations in these antibody scaffolds confer binding to divergent Env strains versus promoting strain-specific binding, fully defining the functional constraints and flexibilities of these CD4bs bnAb classes. The results of this proposal will illustrate a new approach to investigate the evolution and engineering of HIV CD4bs bnAbs, setting the stage for the development of improved immunogens and therapeutic antibodies against HIV. More broadly, the methodological innovation herein will provide a new platform for antibody engineering for the treatment and prevention of various infectious diseases.

Up to $43K

2028-05-31

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Mapping the patterns of hydrology, geochemistry, and plant species distributions that influence abundance and persistence of Puccinellia howellii

National Park Service

FINANCIAL ASSISTANCE: NOTICE OF INTENT TO AWARD. This announcement is not a request for applications. This announcement is to provide public notice of the National Park Service s intention to award a task agreement under a previously competed master cooperative agreement.

Up to $30K

natural resources

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Mapping the sequence-function landscape of a small reactive protein in ultra-high-throughput

NIGMS - National Institute of General Medical Sciences

Project Summary/Abstract Understanding how a protein’s amino acid sequence controls biophysical properties like stability, folding, and reactivity is key to designing better enzymes. However, this task remains challenging due to the complexity of protein conformational ensembles and the scarcity of functional data across sequence space. As a result, computational enzyme design is difficult, and most designed enzymes fail to function without clear indications why. Large-scale experiments can help uncover how specific residues and higher-order interactions affect function, offering the basis for improved computational models and better strategies for enzyme design. However, most surveys of sequence space either cover relatively few variants, or sample only a very narrow region of sequence space deeply. Combining high-throughput functional mapping with de novo design of new enzymes has been out of reach due to the size and complexity of enzymes typically targeted in such experiments. To this end, we propose to map the sequence-function landscape of SpyCatcher, a small reactive protein that forms a covalent bond with its substrate SpyTag, investigating both natural and de novo sequences. While not a true enzyme, SpyCatcher’s small size (80 residues) and simple reaction mechanism make it a tractable minimal model for enzyme-like reactivity. In Aim 1, we will use cDNA display-based to measure the reactivity, substrate binding kinetics, and stability of ~ 1 million natural SpyCatcher variants. The unprecedented scale of these functional measurements on a uniquely simple system will allow us to rigorously explore additive and non-additive sequence-function relationships and identify predictive patterns using machine-learning models. In Aim 2, we will leverage de novo design to explore further reaches of sequence space and test different design strategies in high-throughput, creating SpyCatcher-like proteins with sequences far from natural ones. These designs (three rounds of ~500,000 sequences) will be assayed with the same high-throughput assays to iteratively inform our design process and improve criteria for designing proteins with functional reactivity. We aim to generate high-quality, large-scale datasets spanning both natural and unnatural sequence space in order to uncover fundamental "rules" of reactive protein design, which can inform future engineering efforts. By producing interpretable data that links sequence to biophysical properties, we aim to enhance our ability to design proteins with tailored functions.

Up to $75K

2028-11-30

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Mapping, Condition Assessment, and Interpretive Plan for Bear Lake Mounds Archeological District

National Park Service

The project objective is document, provide cartographic mapping, conduct a detailed condition assessment, and develop an interpretive plan for the Bear Lake Mounds Archeological District in the Flamingo District of the Park

sciencetechnology

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MAPS RFP Draft 5, Virtual Listening Session & Survey!

DEPT OF DEFENSE.DEPT OF THE ARMY.W6QK ACC-APG

MAPS RFP Draft 5, Virtual Listening Session & Survey!

2028-12-31

general

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MAPT-targeting genome editing therapy for Alzheimer's Disease

NINDS - National Institute of Neurological Disorders and Stroke

Alzheimer’s disease (AD) is a devastating condition without effective treatment. Novel approaches to improving treatment are greatly needed. Accumulating evidence suggests tau as a viable target for AD therapy. Recent preclinical studies have shown promise in tau-targeting molecular therapy through suppression of the tau-coding gene MAPT using antisense oligonucleotides (ASOs). These findings have led to clinical tests, showing tau reduction therapy to be generally safe and well-tolerated. However, ASO-based therapy is transient, requiring frequent administration for long-term efficacy. Conversely, CRISPR-based genome editing technology can induce genetic knockouts at the genomic level, offering persistent therapeutic benefits. The most significant hurdle for clinical translation of genome editing therapies has been the lack of safe and efficient delivery methods for the CRISPR machinery to the brain. In this application, we aim to leverage our recent success in development of stimuli-responsive traceless engineering platform ribonucleoproteins (STEP RNPs) for delivery of CRISPR-based genome editing to the brain to demonstrate the potential of tau-targeted genome editing therapy for treatment of AD. In preliminary work, we showed that a single intrathecal administration of genome editing therapy via cRNP, a lead STEP RNP, enabled brain-wide editing of neuronal cells and achieved long-term therapeutic effects for neurodevelopmental diseases. Building on this progress, we propose to optimize STEP RNPs for delivery of genome editing to neuronal cells for tau reduction in Aim 1, to characterize MAPT-targeting genome editing therapy for AD treatment in mouse models in Aim 2 and to preliminarily characterize RNP delivery and tau reduction in nonhuman primates (NHPs) in Aim 3. Successful completion of this application could result in a long-lasting therapy for effective AD management through a single administration and provide a non-viral system for safe and efficient delivery of genome editing to the brain, adaptable for targeting other AD-causing or associated genes.

Up to $1.4M

2031-03-31

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MARAD Maritime Internship

National Park Service

The long term aim of this Task Agreement is the reestablishment of the Maritime Internship program within the Historic American Engineering Record of the National Park Service s Heritage Documentation Programs.

$1 – $15K

Education

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MARAD Ships Documentation

National Park Service

Under this task agreement, Heritage Documentation Programs, Washington, DC, and the Recipient will document architecture and engineering on historical vessels throughout the United States.

$1 – $100K

other

Free to search & build · $99 one-time to unlock the application pack · No subscription

MARBLE VALLEY REGIONAL TRANSIT DISTRICT

Community DevelopmentEquity & Access

Transportation Agency

MARBLE VALLEY REGIONAL TRANSIT DISTRICT

Up to $20K

2026-06-30

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MARC Undergraduate Student Training in Academic Research, Institutional National Research Service Award (NRSA) Research Training Grant (T34)

National Institutes of Health

-The National Institute of General Medical Sciences (NIGMS) will award Minority Access to Research Careers (MARC) Undergraduate Student Training in Academic Research (U-STAR) National Research Service Act (NRSA) Training grants to eligible institutions as a means of supporting undergraduate research training to help ensure that a diverse and highly trained workforce is available to assume leadership roles related to the Nation s biomedical and behavioral research agenda. -The intent of the MARC U-STAR program is to provide competitively trained undergraduate science/math students from minority/minority-serving institutions the opportunity to engage in mentored research, develop the skills and knowledge to successfully pursue Ph.D. degrees and future careers in biomedical and behavioral research, and to strengthen the science course curriculum and research training environment at minority-serving institutions. -This program does not support short-term research training programs at minority-serving institutions of higher education. Note that programs solely for short-term research training should not apply to this announcement but rather the separate (T35) NRSA Short-Term Institutional program (see http://grants1.nih.gov/grants/guide/pa-files/PA-05-117.html).

Healthhealthcare

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March of Dimes — Maternal & Infant Health Grants

maternal healthinfant healthpremature birth

March of Dimes

Funds maternal and infant health research and community programs.

$50K – $250K

Annual

Free to search & build · $99 one-time to unlock the application pack · No subscription

MARCH6-ERAD in hepatic lipid metabolism and MASLD

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

MARCH6-ERAD in hepatic lipid metabolism and MASLD SUMMARY The liver plays a pivotal role in lipid metabolism, and its dysregulation is central to the progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), including steatosis, fibrosis, and nonalcoholic steatohepatitis (NASH). The endoplasmic reticulum (ER) maintains lipid homeostasis, with sterol regulatory element-binding protein 1 (SREBP1) acting as a critical ER-resident transcription factor. Elevated SREBP1 levels drive lipogenesis and hepatic steatosis in MASLD, underscoring the need for tight regulation. While SREBP1 degradation is essential for lipid homeostasis, the mechanisms governing its turnover remain poorly understood. ER-associated protein degradation (ERAD) plays a crucial role in maintaining protein homeostasis, targeting both misfolded and functional proteins for degradation. Among ERAD-specific E3 ubiquitin ligases, MARCH6 is underexplored in the liver, representing a significant gap in understanding hepatic metabolism. Preliminary studies reveal that MARCH6 functions as a sterol sensor, modulating lipid homeostasis through SREBP1 ubiquitination and degradation. Loss of MARCH6 in hepatocytes results in excessive lipid accumulation, increased expression of lipogenic genes, and exacerbated MASLD progression. This research proposes that MARCH6-ERAD serves as a critical negative regulator of lipogenesis, counterbalancing the positive regulation by HRD1-ERAD. To test the hypothesis that MARCH6-ERAD regulates hepatic lipid homeostasis via SREBP1 ubiquitination and degradation, this study proposes two specific aims: Determine the functional significance of MARCH6-ERAD in maintaining lipid homeostasis and its role in MASLD. This aim will explore the responsiveness of MARCH6 to metabolic signals, establish its role as a regulator of lipid synthesis and uptake, and assess its therapeutic potential in MASLD (Aim 1). Establish the role of MARCH6-ERAD in regulating lipid metabolism through SREBP1 ubiquitination and degradation. This aim will confirm SREBP1 as a substrate of MARCH6, delineate the ubiquitination-degradation mechanism, and assess its impact on MASLD (Aim 2). This study will provide groundbreaking insights into the post-translational regulation of hepatic lipid metabolism, positioning MARCH6-ERAD as a sterol sensor and a critical factor in preventing MASLD progression. RELEVANCE TO HUMAN HEALTH: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a growing global health concern linked to obesity and diabetes. This study investigates the role of MARCH6-ERAD as a critical regulator of hepatic lipid metabolism, demonstrating its ability to modulate SREBP1 degradation and maintain lipid homeostasis. By uncovering MARCH6's therapeutic potential, this research aims to inform novel strategies to prevent or treat MASLD and improve patient outcomes.

Up to $662K

2031-03-31

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Marcus Foundation Jewish & Community Grants

Jewish educationIsraelveterans+2

Marcus Foundation (Bernie Marcus)

Co-founded by Home Depot co-founder. Supports Jewish education, Israel, veterans, autism, and free enterprise programs.

$25K – $1M

Rolling

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Margaret and Wallace McCain Family Foundation

early-childhoodEducationchild-development

Margaret and Wallace McCain Family Foundation

Supports early childhood education and development programs across Canada, with particular focus on evidence-based approaches.

$10K – $500K

Rolling

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MARGINS Program

U.S. National Science Foundation

The MARGINS program was initiated by the scientific community and the National Science Foundation and has been designed to elevate our present largely descriptive and qualitative knowledge of continental margins to a level where theory, modeling and simulation, together with field observation and experiment, can yield a clearer understanding of the processes that control margin genesis and evolution. Although continental margins have been traditionally assigned to three distinct tectonic settings, i.e., convergent, divergent and translational, the approach used by the MARGINS program recognizes that a range of fundamental physical and chemical processes that form and deform the surface of the Earth operate at all margins. Tectonic setting may govern the specific expression of a particular process that may vary in different environments. However, a relatively small number of processes, i.e., lithospheric deformation, magmatism, other mass/energy fluxes, sedimentation, and fluid flow, are fundamental to the evolution of the margins. Study of these basic processes, wherever they are best expressed, provides a more logical line of inquiry for understanding the complex nature of continental margins.This process-oriented approach to understanding the entire system of margin evolution requires broadly based interdisciplinary studies and a new class of major experiments. The MARGINS science plan, developed from a series of well attended workshops over the past decade, advocates concentration on several study areas (focus sites) targeted for intensive, multidisciplinary programs of research in which interaction between field experimentalists, numerical modelers and laboratory analysts would occur. MARGINS fosters the involvement of a broad cross-section of investigators in focused, multidisciplinary experiments at these focus sites, to achieve the objectives that could not be accomplished otherwise. Thus the MARGINS Program concentrates on four scientific initiatives at these focus sites - this list will be periodically reviewed and modified.Rupturing Continental Lithosphere Experiment (RCL) ?? Gulf of California and Red Sea focus sitesSubduction Factory Experiment (SubFac) ?? Izu-Bonin-Marianas and Nicaragua-Costa Rica focus sitesSeismogenic Zone Experiment (SEIZE) ?? Nankai and Nicaragua-Costa Rica focus sitesSource-to-Sink Experiment (S2S) ?? Fly River/Gulf of Papua New Guinea and Waipaoa River New Zealand focus sitesInformation and a science plan for the program detailing each initiative can be found on the MARGINS website at http://www.margins.wustl.edu/Home.html. The expected level of funding will be approximately $6.0 million per year for the foreseeable future.

$500K