Grants

18,711 grants found

24 grants worth up to $5.0M match your search

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Manufacturing Extension Partnership (MEP) Center for Nebraska

National Institute of Standards and Technology

NIST invites applications from eligible applicants for funding projects that provide manufacturing extension services to primarily small- and medium-sized manufacturers in the United States. Specifically, NIST seeks applications to re-establish an MEP center in Nebraska.

rolling

sciencetechnology

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

Manufacturing Extension Partnership (MEP) Centers for Arizona, Maryland and Rhode Island

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National Institute of Standards and Technology

NIST invites proposals from eligible proposers for funding projects that provide manufacturing extension services to primarily small- and medium-sized manufacturers in the United States. Specifically, NIST seeks proposals for projects to establish MEP centers in Arizona, Maryland and Rhode Island.

rolling

sciencetechnology

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

Manufacturing Extension Partnership (MEP) Centers for South Dakota and Kentucky

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National Institute of Standards and Technology

NIST invites proposals from eligible proposers for funding projects that provide manufacturing extension services to primarily small- and medium-sized manufacturers in the United States. These projects will establish MEP centers in South Dakota and Kentucky.

rolling

sciencetechnology

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

Manufacturing Extension Partnership (MEP) Projects - Growth Transformation

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National Institute of Standards and Technology

The National Institute of Standards and Technology (NIST) invites proposals from qualified organizations for projects that address new and emerging competitive needs of manufacturers in areas consistent with the NIST MEP Program s five Strategic Growth Areas (Supply Chain, Sustainability, Technology Acceleration, Workforce and Continuous Improvement). Funded projects will improve the competitiveness of industries in the applicant s region, and contribute to the long-term economic stability of the region. Please see the NIST MEP website, www.nist.gov/mep for details on these strategies. Competitive projects will use innovative or collaborative approaches to develop and demonstrate integrated tools, training and methodologies for growth transformation that meet the Strategic Growth Area needs and to share those approaches with the MEP National System. It is important that these awards be well aligned with the MEP national system of extension service providers in order to maximize the potential and impact of existing resources available to manufacturers through the MEP Program. Further information regarding this MEP Program is provided in the information packet, which can be obtained at www.grants.gov with additional background information provided at www.nist.gov/mep. The proposal should include plans for integration into the MEP national system and linkages to appropriate national resources.

rolling

other

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

Manufacturing Extension Partnership (MEP) Projects - Strategic Growth Areas

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National Institute of Standards and Technology

The National Institute of Standards and Technology invites proposals from eligible organizations for projects to develop client engagement or business models and deployment strategies that integrate two or more of the MEP Strategic Growth Areas. The projects should further demonstrate in its proposed client engagement or business model, the benefit of this integration and how the approach can expand service capability and capacity of the MEP system. The five MEP Strategic Growth Areas are: supply chain, sustainability, technology acceleration, workforce and continuous improvement. Proposals should include a plan, a client engagement or business model and deployment strategy for the project, and an approach for leveraging existing tools, resources and partnerships. The objective of these projects is to demonstrate the ability to strengthen, through an integrated transformational growth services model, the global competitiveness of small- and medium-sized U.S. based manufacturing firms. Project specific performance measurement and management approaches, including key milestones, are crucial to the evaluation of these projects. NIST is seeking projects that present novel and new approaches to delivering and communicating performance measurement and evaluation. For example, those projects that incorporate the following factors will be considered competitive: internal performance measurement for management control, external evaluation for assessing outcomes of the activity, and customer satisfaction measures of performance. This could include approaches to gathering outcome information, comparisons of outcomes achieved by project clients or other approaches to performance measurement and evaluation. The MEP program places high importance on ensuring that projects be well aligned with the work of MEP service providers in order to maximize the potential and impact of existing resources. Additional background information on MEP service providers is provided at http://www.nist.gov/mep.

rolling

other

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Manufacturing Machines and Equipment

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U.S. National Science Foundation

The MME program supports fundamental research leading to improved manufacturing machines and equipment, and their application in manufacturing processes. Key goals of the program are to advance the transition of manufacturing from skill-based to knowledge-based activities, and to advance technologies that will enable the manufacturing sector to reduce its environmental and societal impacts. A focus is on the advancement of manufacturing machines and related systems engineering that will enable energy manufacturing on a large scale. The program also supports research on additive manufacturing machines and processes encompassing feature scales from microns to meters (nanometer scale additive manufacturing is supported under the Nanomanufacturing program).Investigators wishing to serve on a proposal review panel should email the Program Director with a short biographical sketch, a list of areas of expertise and a link to their home page. REU/RET supplement requests should be submitted by March 31 each year.

$1 – $300K

rolling

sciencetechnology

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

Manufacturing Systems Integration

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U.S. National Science Foundation

Manufacturing Systems Integration

Rolling

STEM

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

Manufacturing Systems Integration

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U.S. National Science Foundation

The Manufacturing Systems Integration (MSI) Program supports fundamental research addressing the opportunities and challenges that digital technologies present for the next industrial revolution, with particular emphasis on the digital integration of design and manufacturing within the larger life cycle ecosystem. Manufacturing Systems Integration proposals should address underlying principles and advances that are generalizable for globally competitive and world leading industries. Connectivity, automation, and secure collaboration are examples of areas that are integral to digital environments capable of supporting the innovation, realization and sustainment of manufactured products and systems in the value creation process. Fundamental generalizable research for manufacturing systems integration might include, for example: <ul type="disc"> <li>Digital representation, protocols, and/or processes for integration and collaboration in manufacturing systems (machines and/or humans)</li> <li>Intelligent self-organizing production systems</li> <li>Ease of use, interoperability and seamless integration of technologies, machines, and humans</li> <li>Service-oriented architectures and systems</li> <li>Data sets that are compatible and usable across platforms</li> <li>Reliable and secure communications within and across the manufacturing value chain</li> <li>Integration of distributed manufacturing systems across time and space, including incorporating both legacy and leading-edge equipment and technologies</li> <li>Methods for assessing the impact and value of externalities throughout the life cycle within the digital environment</li> </ul> Interdisciplinary, convergent proposals that bring diverse perspectives, populations, disciplines, and capabilities together are welcome. It is strongly encouraged and expected that investigators discuss their ideas with a MSI program director well in advance of proposal submission.

Rolling

science_technology_and_other_research_and_development

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

Manufacturing Systems Integration

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U.S. National Science Foundation

The Manufacturing Systems Integration (MSI) Program supports fundamental research addressing the opportunities and challenges that digital technologies present for the next industrial revolution, with particular emphasis on the digital integration of design and manufacturing within the larger life cycle ecosystem. Manufacturing Systems Integration proposals should address underlying principles and advances that are generalizable for globally competitive and world leading industries. Connectivity, automation, and secure collaboration are examples of areas that are integral to digital environments capable of supporting the innovation, realization and sustainment of manufactured products and systems in the value creation process. Fundamental generalizable research for manufacturing systems integration might include, for example: Digital representation, protocols, and/or processes for integration and collaboration in manufacturing systems (machines and/or humans) Intelligent self-organizing production systems Ease of use, interoperability and seamless integration of technologies, machines, and humans Service-oriented architectures and systems Data sets that are compatible and usable across platforms Reliable and secure communications within and across the manufacturing value chain Integration of distributed manufacturing systems across time and space, including incorporating both legacy and leading-edge equipment and technologies Methods for assessing the impact and value of externalities throughout the life cycle within the digital environment Interdisciplinary, convergent proposals that bring diverse perspectives, populations, disciplines, and capabilities together are welcome. It is strongly encouraged and expected that investigators discuss their ideas with a MSI program director well in advance of proposal submission.

rolling

sciencetechnology

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

Manufacturing Technology Acceleration Center (M-TAC) Pilot Projects

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National Institute of Standards and Technology

NIST invites proposals from eligible applicants to conduct approximately two (2) pilot projects that will inform future NIST investment leading to the development of a network of Manufacturing Technology Acceleration Centers (M-TACs). The emphasis of these pilots will be to demonstrate the conduct of technology transition and commercialization activities with small and mid-sized U.S. manufacturers to foster their readiness to adopt and/or adapt advanced technologies into their manufacturing processes and products. The pilots will specifically focus on addressing the technical and business challenges encountered by small and mid-sized U.S. manufacturers as they attempt to integrate, adopt, transition, and commercialize both existing and emerging product and process technologies into their operations to help them grow and compete within manufacturing supply chains as innovative, value-adding components of our nation s economy.These pilots will be operated by existing Manufacturing Extension Partnership (MEP) Centers and are expected to work in collaboration with other existing resources, including research consortia and institutions such as those operating as part of or in conjunction with the National Network for Manufacturing Innovation (NNMI), state and local technology-based economic development intermediaries, industry associations, industry-university partnerships, and manufacturing organizations. The pilots will create and test business models for potential, future operationalized M-TACs that can scale up on a national level to serve the needs of significant numbers of small and mid-sized manufacturers on the order of thousands on an annual basis. The pilots will also document successes and challenges.

rolling

sciencetechnology

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MAP Fund Performance Grant

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MAP Fund

Grants for the creation and development of new live performance works that are artistically excellent and socially relevant.

$10K – $60K

2026-10-15

performancelive art

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

MAP International Medical Aid Grants

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MAP International

Provides medicines, medical supplies, and health programs to people in need in 100+ countries. Focus on disease prevention and treatment.

$10K – $200K

Rolling

medical aidmedicineshealth programs+1

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Map Validation at Organ Pipe Cactus NM.

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National Park Service

The goal of this project is to partner with the recipient to support research internships with undergraduate-level students to conduct work related to vegetation mapping for management and planning purposes, at Organ Pipe Cactus National Monument, as part of the NPS Vegetation Inventory.

$1 – $41K

rolling

natural resources

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

MAPK signaling cascade: multi-stability and dynamic information transfer

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NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ABSTRACT Inflammation is a natural physiological process that initiates and orchestrates the immune response, but an overreaction in magnitude or time can have serious health consequences, including death. Inflammation is initiated when immune sentinel cells, especially macrophages, sense the presence of pathogen or tissue damage and produce inflammatory cytokines. Recipient cells respond to those cytokines by adapting their functions via induced gene expression programs. The signaling pathways associated with inflammation are NFκB and MAPK. The NFκB pathway controls the cellular response to inflammation signals: our recent studies have revealed that the dynamics of NFκB activity is stimulus-specific and robustly distinguishes between different ligands and doses (Immunity 2021; 54:916, Science 2021; 372:1349). In contrast, whether inflammatory cytokines are secreted by macrophages is controlled by MAPK activities p38 and ERK (Cell Syst 2017; 4:330, Genes Dev 2014; 28:2120). Our recent studies found that MAPK p38 activation shows remarkably high heterogeneity (MSB 2024; 9:898), suggesting that the functional role of high MAPK heterogeneity is to limit the production of inflammatory cytokines to a minority of cells, thereby reducing the risk of inflammatory overload. However, what controls the heterogeneity of MAPK signaling remains unclear. An overarching hypothesis of this proposal is that the heterogeneity of MAPK p38 and ERK signaling is the result of the topology and mechanism of the biochemical network that controls activation of these kinases. Specifically, we hypothesize that the two layers of dual-phosphorylation kinase cascades generate a complex multi-stability landscape that can exacerbate molecular noise to generate cell-to-cell heterogeneity. To address this hypothesis, we will investigate both noise exacerbation and buffering emerging from intrinsic characteristics such as the number and relative position of the available stationary states, determined by the kinetic parameters of each pathway and strength of external signals. This will allow us to characterize, through experimentation and detailed biochemical mechanistic modeling, how stimulus information transmission and stimulus-response activities of MAPK p38 and ERK pathways avoid inflammatory overreaction through cell-to- cell variability. By pursuing both synergistic approaches in parallel we will gain a deep understanding of how noisy cytokine secretion is controlled and identify novel strategies of analysis, diagnostics, therapeutics.

Up to $191K

2028-01-31

health research

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

Maple Leaf Park Slope and Meadow Restoration

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Friends of Maple Leaf Reservoir Park

Friends of Maple Leaf Reservoir Park intend to 1) hire a restoration company to remove invasive and exotic species in the eastern 11,000 sf of zone 2 of the approved Habitat Enhancement plan. 2) Increase density of native meadow wildflowers in the tall grass meadows of the upper park.

Up to $18K

Rolling

general

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

Maple Leaf Summer Social 2023

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Maple Leaf Community Council

The Maple Leaf Summer Social 2023 is a free and public party in Maple Leaf Reservoir Park featuring food (including LOTS of free ice cream), games, music, art, and most importantly, the opportunity for participants to make vital post-pandemic connections with old and new neighbors.

Up to $23K

Rolling

artsAgriculture

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

Mapping Activated Microglia and Their Effect on Cognitive Deficits in Adults with Sickle Cell Disease

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NHLBI - National Heart Lung and Blood Institute

Project Summary Sickle cell disease (SCD) is associated with progressive cognitive deficits beginning in infancy and which cause significant impacts on academic achievement and later job attainment. Increasingly there is evidence from preclinical SCD mice and other human neurodegenerative disorders that neuroinflammation, and specifically activated microglia, independently contribute to these cognitive deficits. Recent advances in diffusion MRI (dMRI) have led to validated neuroimaging biomarkers of neuroinflammation. When microglia are activated, alterations in cell shape and density can be detected based on changes in water dispersion within and around microglia. We hypothesize that individuals with SCD have a significantly greater density and distribution of global and regional activated microglia, particularly in the hippocampus and frontal lobes compared to healthy controls and that the density of activated microglia is inversely correlated with executive functioning and attention abilities. In this proposal, we aim to: 1) measure the density and distribution of regional and whole brain activated microglia in 45 individuals with SCD compared to 15 healthy controls frequency matched for age, sex, and race using this novel dMRI sequence; and 2) determine the correlation between global and/or regional activated microglial density and the presence of cognitive deficits using the NIH Toolbox: Cognition Battery. Finally, in an exploratory aim, we will quantify systemic inflammatory and neurodegeneration markers and will assess for correlation with the density of activated microglia in all study subjects. In the long term, the knowledge gained from this study will have both clinical and investigational implications, to monitor for and follow the development of neuroinflammation in the brains of individuals with SCD and as a means for assessing response to interventions targeting neuroinflammation and cognitive deficits. Dr. Karkoska’s long-term goal is to become an independent investigator focused on understanding the pathophysiology of cognitive deficits in adults and children with SCD and identifying/implementing interventions to slow or even prevent SCD-related cognitive decline. She will pursue the following career development objectives during her K23 training through a combination of formal coursework, practical experiences with mentors/collaborators, and conference/seminar attendance: 1) focus on the design and implementation of translational and multisite research trials; 2) acquire skilled training and collaboration in advanced neuroimaging techniques, processing, and analysis as a foundation for future independent study design; and 3) obtain formal training in cognition and neuropsychological battery selection and interpretation. The completion of these objectives, along with the study aims will place Dr. Karkoska in the ideal position to apply for NIH R-level funding during this proposed funding mechanism.

Up to $187K

2031-03-31

health research

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

Mapping anti-filovirus humoral immune responses in broadly seroreactive individuals

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NIAID - National Institute of Allergy and Infectious Diseases

Project Summary/Abstract: Filoviruses encompass a broad group of highly lethal pathogens, including orthoebolaviruses (Ebola (EBOV), Bundibugyo, Sudan, and Taï Forest viruses) and orthomarburgviruses (Marburg (MARV) and Ravn viruses). These viruses cause sporadic disease outbreaks, but which virus will emerge and where cannot be predicted. As such, residents of affected areas, as well as military, aid workers and travelers in Central and West Africa continue to be at risk of infection. Further, currently approved monoclonal antibody (mAb) treatments and vaccines are available only for EBOV. A few known mAbs can cross-react among orthoebolaviruses, but none are yet known to offer broad filovirus neutralization. It is possible that our ability to uncover human mAbs of broad neutralization was limited by the nature of the human samples used for discovery. Prior antibody discovery campaigns to date isolated antibodies from individuals who had been infected once with just one of these viruses (usually EBOV, one with MARV, etc.), and many studies were performed on returning Americans who would not have had more than one filovirus exposure. This proposal, however, utilizes a different cohort. Serology studies in the Democratic Republic of the Congo, where multiple filoviruses are endemic, revealed 23 individuals with extraordinarily broad and strong antibody responses against a broad range of filovirus surface glycoproteins (GP). Some of these individuals have strong reactivity to all of them: all four pathogenic orthoebolaviruses and both orthomarburgviruses. These individuals have lived all or most of their lives in remote villages that have had known outbreaks and have occupations that likely led to multiple filovirus exposures over time. In this project, we will analyze, in detail, the antibody repertoires of these multiply exposed individuals. We will analyze reactivity at the polyclonal and monoclonal levels alike. We expect that mAbs identified in these individuals will have greater breadth and broader filovirus activity than have been discovered before. The results from this study could lead to the discovery of a novel, broad-spectrum filovirus mAb therapeutic, guide the development of more broadly applicable vaccines, and will deepen our understanding of how a lifetime of exposure shapes the humoral immune response to these viruses.

Up to $279K

2028-03-31

health research

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

Mapping Cardiovascular and Infectious Risk of JAK inhibitors in patients with Rheumatoid Arthritis: Comparative Safety

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NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases

PROJECT SUMMARY/ABSTRACT Janus kinase inhibitors (JAK}---including tofacitinib, baricitinib, and upadacitinib-have emerged as promising oral treatment options for patients with rheumatoid arthritis who experience an inadequate response to conventional therapies. However, major safety concerns, including increased risk of cardiovascular events, venous thromboembolism, and serious infections, have prompted FDA black box warnings and remain major barriers to widespread use. These safety concerns largely stem from potential signals in integrated analyses of premarketing studies and the ORAL Surveillance trial, which reported a dose-dependent elevated risk of cardiovascular and thromboembolic events with tofacitinib compared to tumor necrosis factor (TNF) inhibitors. However, the ORAL trial has left some critical questions unanswered-specifically, whether the observed risk elevation is attributable to a specific JAK inhibitor toxicity, a protective effect of TNF inhibitors, or both; or how the safety profile of specific JAK inhibitors may compare to approved alternatives, such as interleukin-6 inhibitors. Approved JAK inhibitors have differences in selectivity and target binding affinity, which may translate into differences in adverse health outcomes. As a pan-JAK inhibitor, tofacitinib targets multiple JAK isoforms (JAK1, JAK2, JAK3), while newer agents such as upadacitinib and baricitinib exhibit greater selectivity for JAK1. The current FDA black box warning applies to all JAK inhibitor class members, but comparisons among specific class members are lacking. Moreover, all currenUy approved JAK inhibitors are metabolized via cytochrome P450 3A4 (CYP3A4), making them susceptible to clinically significant drug-drug interactions {DDls). Co-administration with moderate or strong CYP3A4 inhibitors, such as diltiazem, can substantially increase plasma JAK inhibitor concentrations, and potentially increasing the risk of adverse events. In this R01, we propose a comprehensive examination of the safety of JAK inhibitors among patients with rheumatoid arthritis. We will use the estimand framework and target trial emulation methods to compare cardiovascular, thrombotic, and infectious risks between JAK inhibitors and other commonly used therapies, overall and by agent. We will also evaluate how co-prescribed CYP3A4 inhibitors modify these risks. Our findings will directly inform clinical guidelines and prescribing decisions for patients with rheumatoid arthritis.

Up to $3.2M

2030-05-31

health research

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

Mapping cerebellar influence in FTD: unraveling the role of the cerebellum in social cognition and clinical trajectory

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NIA - National Institute on Aging

PROJECT SUMMARY/ABSTRACT Behavioral variant frontotemporal dementia (bvFTD) is a devastating neurodegenerative disorder characterized by early and profound social cognitive deficits, including impairments in theory of mind, emotion reading, and empathy, which cause significant distress and burden for caregivers. While research has traditionally focused on cortical degeneration in bvFTD, mounting evidence highlights the cerebellum’s critical role in cognitive and social processing. Despite comprising 80% of the brain’s neurons and demonstrating early atrophy in bvFTD, the cerebellum’s contributions to social cognition and its potential as a biomarker for disease progression remain underexplored. This study aims to address this gap by investigating the cerebellum’s influence on social cognitive deficits and its value for predicting clinical trajectories in bvFTD. Leveraging cross-sectional and longitudinal neuroimaging and clinical data from the University of California San Francisco (UCSF), Memory and Aging Center and the multisite ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study, this project is structured to achieve two primary aims. Aim 1 will use cross-sectional data from UCSF to characterize the relationship between social cognition and cerebellar structure and function in bvFTD across disease stages, using neuroimaging to identify compensatory and degenerative mechanisms. Aim 2 will use longitudinal data from ALLFTD to assess the predictive value of early cerebellar atrophy for later social, cognitive, and psychiatric decline, enhancing understanding of the cerebellum’s impact on clinical outcomes. This research is poised to fill critical gaps in our understanding of bvFTD by highlighting the cerebellum’s involvement beyond traditional motor functions, thereby offering new insights into brain network dynamics and their clinical implications. Findings from this study have the potential to enhance diagnosis and inform novel intervention strategies targeting cerebellar circuits, ultimately enhancing patient management in bvFTD. This project supports Dr. Chen’s career development goals of becoming an independent researcher specializing in advanced quantitative neuroimaging and neuropsychology in individuals with neurodegenerative disease. The K99 phase will provide training in cognitive neuroscience, interpretation of social cognition testing, and multimodal neuroimaging, enhancing her ability to integrate clinical and neuroimaging data to study neurodegenerative disease mechanisms. The R00 phase will support the establishment of her research program at a leading academic institution, leveraging advanced neuroimaging techniques to address key questions in dementia diagnosis, disease monitoring, and intervention. Dr. Chen’s training will take place in a highly collaborative, resource-rich environment at UCSF, which offers cutting-edge neuroimaging facilities, access to a well- characterized dementia cohort, and mentorship from experts in neurodegeneration, social cognition, and imaging analytics. This comprehensive training will position her to lead an impactful independent research program that advances our understanding of bvFTD and related neurodegenerative disorders.

Up to $120K

2028-02-29

health research

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

Mapping HIV reservoir establishment in human tonsil organoids

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NIAID - National Institute of Allergy and Infectious Diseases

Project Summary Combination antiretroviral treatment has transformed HIV (Human immunodeficiency virus) infection from a fatal disease to a manageable chronic condition. It requires, however, regular antiretroviral medication. Attempts to cure HIV fall short because of the existence of long-lived HIV reservoirs comprised of cells harboring non- productive proviruses. While HIV is integrated into the genome of these cells, no viral proteins are expressed, leaving the cells indistinguishable from uninfected cells, preventing clearance by antiviral treatments or the immune system. My proposal seeks to define the properties and features of nonproductively infected cells circulating in the blood or residing in lymphoid tissues. My project will leverage a dual-reporter virus which allows for the physical separation of cells nonproductively infected with HIV from those that are productively infected and uninfected cells. Additionally, we have worked to develop methods of culturing and infecting lymphoid cells derived from human tonsils to mimic infection in tissues. Utilizing these model systems, we will work to understand cellular and viral factors which influence nonproductive HIV infection. In Specific Aim 1, I will utilize spectral flow cytometry to phenotype the cell types present in our tonsil organoid model, delineating the cells that harbor non-productive proviruses. We will compare these results to those found in blood derived CD4+ T cells and measure the impact of other bystander cell types on the relative frequency of productive to non-productive infections. We will use RNA sequencing to compare the transcriptomic landscapes of nonproductively infected cells to those of productively infected cells. In Specific Aim 2, we will utilize established and novel techniques to identify viral characteristics which correlate with nonproductive HIV infection. We will use digital PCR technologies to measure proviral intactness, and parallel sequencing techniques to identify HIV integration sites. These experiments will collectively identify host and viral factors which play a role in HIV latency establishment in relevant primary human cells and organoid model systems. This research will be supervised by Dr. Viviana Simon, a recognized leader in the field of virology. I will additionally be aided by esteemed collaborators both at our institution and beyond, who will assist with technical aspects as well as my development as a budding researcher. My fellowship proposal will generate new insights into the non-productive HIV reservoir, provide opportunities to learn advanced techniques both on the bench and in data analysis, and prepare me for a successful career as an independent academic researcher and mentor.

Up to $50K

2029-05-31

health research

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

Mapping How Trajectories of Perinatal Substance Use and Depression Impact Neonatal Brain Development

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NIDA - National Institute on Drug Abuse

PROJECT SUMMARY/ABSTRACT The perinatal period is marked by heightened vulnerability to mental health challenges, with perinatal substance use (PSU) and perinatal depression (PD) presenting significant concerns for maternal well-being and child development. PSU and PD often co-occur and pose bidirectional risks that exacerbate caregiving challenges. Despite evidence of their influence and overlap, research has yet to investigate how the interplay between PSU and PD impacts infant hippocampal development. Prior work in this area has been limited by assuming uniform impacts across the perinatal period and neglecting to evaluate these dynamic and bidirectional risk factors within the same model. Moreover, insights into how characteristics of PSU and PD (e.g., intensity, comorbidity, chronicity) may modify risk for development remains highly debated. To address these gaps, this study will be the first to model the longitudinal interplay between PSU, PD, and their combined impact on infant brain development. We hypothesize that utilizing person-centered, longitudinal, data-driven trajectories, rather than relying on static global reference values or clinical cutoffs, will provide more clinically valuable metrics for intervention, fostering intergenerational benefits. This study aims to (1) Characterize the interplay between PSU and PD and their reciprocal unfolding over the perinatal period. Specifically, testing whether within- or between-subjects models better capture the bidirectional interplay and change between PSU and PD across time to identify key windows and metrics of risk. (2a) Examine the impact of PSU/PD comorbidity on infant hippocampal volume and growth and test whether within- or between-subjects models better capture risk for offspring neurodevelopment. (2b) Compare models informed by developmental theory (Mismatch vs. Cumulative Stress vs. Mood Entropy) to evaluate which best characterizes the impact of PSU/PD on neurodevelopment in the first year of life. This research is responsive to the goals of NIDA’s 2022-2026 strategic plan to leverage data science to understand real-world complexity—including how comorbid mental health conditions and risk and protective factors interact to influence drug-related outcomes. Findings have the potential to refine screening practices, optimizing their timing and content to identify at-risk individuals more effectively. This work could ultimately enhance the capacity of healthcare systems to deliver timely and targeted interventions, improving health outcomes for families impacted by PSU and PD and reducing intergenerational consequences.

Up to $107K

2028-02-14

health research

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

Mapping MicroRNA-target Interactions in the Zonated Liver

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NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

ABSTRACT The lens of metabolic zonation is extremely pertinent to liver pathophysiology, and can be applied to both acute and chronic/progressive conditions like acute liver damage and MASLD/MASH. The long term goal is to better understand the role of microRNAs in liver physiology, microRNA dysregulation in pathophysiology, and to improve clinical outcomes for patients with acute and chronic liver diseases. The overall objective of this application is to unravel the specific mechanism by which microRNAs maintain metabolic zonation by mapping and validating microRNA-target interactions across the lobule with high fidelity to identify new biomarkers and inform therapeutics in the context of the healthy and diseased liver. The central hypothesis is that the phenomenon of metabolic zonation is at least partially controlled by miRNA-target networks that can be taken advantage of both therapeutically and diagnostically. The central hypothesis will be tested by pursuing two specific aims: 1) Mapping and validation of miRNA-target interactions in liver cells along the lobular axis with high fidelity and 2) Assessing dysregulation of miRNA-target networks in a model of acute and chronic liver disease. Under the first aim, we will use Spy3-Ago2-pulldown and sequencing (SAPseq) in mice with a Cre-inducible Spy3-tag on microRNA effector protein Ago2 (Cre +iSpy mice) to create a single high-fidelity map of differential miRNA-target regulation in spatially sorted hepatocytes, validate miRNA zonation using miRNA-sensing reporter constructs and independently validate node-level and global miRNA-target interactions using N-acetylgalactosamine conjugated miRNA sponging ASOs and vectors that deliver miRNA-blocking peptide ddT6B. For the second aim, we will use spatial sorting and SAPseq to evaluate miRNA-target changes in response to pericentral toxin APAP and periportal toxin allyl alcohol over time in Cre+ iSpy mice, miRNA-target changes in Cre+ iSpy mice fed a choline-deficient, L-amino acid defined, high fat diet over time (induces MASLD/MASH), and use serum SAPseq to evaluate circulating miRNA changes in both conditions. Our proposal is innovative as it utilizes technical advances in microRNA biology and Ago2 structure to expand our understanding of liver physiology with applications in addressing pathologies. Ultimately, this work will have a significant, direct, and positive impact in improving treatment options for patients with chronic liver diseases and diagnostics for acute liver diseases. Beyond the liver, it will have wide-reaching effects in the fields of cell, gene, and immunotherapy. The proposed work will be conducted at The Scripps Research Institute, under guidance of mentors in RNA biology, liver biochemistry, and clinical care. This proposal will be vital to supplement my dual-degree training to become an independent physician-scientist and domain expert in clinical RNA biology.

Up to $37K

2030-04-30

health research

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

Mapping mitochondrial NADPH utilization by exploiting hypomorphic variants of NADK2

open

NINDS - National Institute of Neurological Disorders and Stroke

PROJECT SUMMARY Mitochondria are multifaceted organelles responsible for cellular energy production and nutrient catabolism, efficiently performing these tasks as distinct metabolic compartments. Such compartmentalization requires fine- tuned regulation of not only catabolic enzymes but also their associated co-factors. One such compartmentalized co-factor is nucleotide adenosine diphosphate phosphate (NAPDH), which enables numerous metabolic pathways within mitochondria including unsaturated fatty acid oxidation, lysine catabolism, type II fatty acid synthesis, and proline biogenesis, amongst others. Due to its broad utilization, perturbation of NADPH synthesis would have widespread, detrimental effects on mitochondrial metabolism. Indeed, human mutations in a key NADPH-producing enzyme, NADK2, can lead to Progressive encephalopathy with leukodystrophy due to DECR deficiency, an ultra-rare disease presenting with failure to thrive, pronounced hypotonia, and microcephaly. However, a recently identified patient harboring hypomorphic NADK2 alleles presented with a much milder disease profile and only select metabolic defects, suggesting that full loss of NADK2 broadly compromises mitochondrial metabolism, while partial loss of NADK2 affects only select pathways. We hypothesize that mild- to-intermediate loss of NADPH production disproportionately affects select pathways to spare more “essential” pathways, leading to a “priority code” of mitochondrial co-factor usage. As NADK2 represents a central NADPH- producer within mitochondria, we propose that an in-depth functional assessment of disease-associated NADK2 variants will illuminate a “priority code” for mitochondrial NADPH allocation, while simultaneously providing a mechanistic framework to understand disease heterogeneity. In this proposal, we will generate a series of cell lines that harbor NADK2 variants of uncertain significance with different predicted mutational burdens: low, moderate, or high. We will first establish and characterize these mutants by expressing each variant in NADK2 knockout HAP1 cells and measuring the extent to which these mutants can rescue mitochondrial respiration as well as organellar and cellular NADPH levels. We will then profile these cell lines with multiomic analyses of lipids and metabolites to understand the extent to which metabolic pathways become compromised upon limiting NADK2-produced mitochondrial NADPH. Completion of the proposed work will, as a proof of principle, demonstrate the power of cellular models of rare disease, as well as the breadth of dysfunction associated with specific mutational burdens, which could inform accurate diagnoses or therapeutic options for patients with NADK2 or DECR deficiency. Furthermore, these cells will provide a comprehensive toolkit to study how NADPH perturbations affect mitochondrial metabolism, providing a rich dataset of the dynamic nature of organelle-wide NADPH-consuming pathways.

Up to $156K

2028-05-31

health research

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