Grants

16,469 grants found

24 grants worth up to $6.4M match your search

Enter your email to see grant names, funders, and application links

Notice of Request for New Informaiton Collection; Urban Agriculture and Innovative Production (UAIP) Grants

Agriculture Department

In accordance with the Paperwork Reduction Act of 1995, this notice invites the general public and other public agencies to comment on this proposed information collection. This collection is a revision of a currently approved collection; for reporting progress on a Urban Agriculture and Innovative Production Grant.

See notice

Agriculture

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

Notice of Rescission of Funding Opportunity for the Rural Energy for America Program

open

Agriculture Department

The Rural Business-Cooperative Service (RBCS or the Agency), a Rural Development (RD) agency of the United States Department of Agriculture (USDA) issued a Notice of Funding Opportunity (NOFO) published in the Federal Register (FR) at 89 FR 83449 on October 16, 2024 to announce acceptance of grant, guaranteed loan, and combined grant and guaranteed loan applications under the Rural Energy for America Program (REAP). The NOFO was issued for Fiscal Years (FY) 2025, 2026, and 2027. The purpose of this notice is to rescind the October 16, 2024, NOFO. The Agency is currently promulgating regulatory changes to the REAP program and available funding will be announced after publication of said changes. Applicants who previously submitted applications will be required to submit a new application and must comply with the new regulation. This applies to any applicant that does not possess a fully executed Financial Assistance Agreement. As provided for in 7 CFR 4280.122 and 7 CFR 4280.156, the Agency, by this notice, is providing alternate procedures for processing applications. Grant applications will be processed according to the funding notice that will be available on the Agency website after the new regulations are issued.

See notice

Agriculturerural development

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

Notice of Technical Assistance for Remote Alaska Communities Energy Efficiency Competition

open

Golden Field Office

Modification 3: The purpose of this amendment is to divide Phase 2 of the NOTA into two topic areas. The Phase Areas and Scope of Activities , the Content and Form of the Application and the Review Criteria sections of the NOTA have all been modified to account for dividing Phase 2 into 2 topic areas. Additional language was added to clarify allowable TA for integrated renewable energy. Modifications to the NOTA have been highlighted in yellow. All other parts of the NOTA remain unchanged. Modification 2: The Purpose of this amendment is to extend the deadline for submitting applications for Pledge Designation (Phase 1) until 5 p.m. ET on February 2, 2016. The purpose of the Modification is to revise the Pledge Form.The purpose of this Notice of Technical Assistance (NOTA) is to support the goals of the Department of Energy s (DOE) Remote Alaskan Communities Energy Efficiency Competition (RACEE Competition), announced by President Obama. The RACEE Competition will empower Alaskan communities and native Alaskan villages to develop effective tools to advance the use of reliable, affordable, and energy efficient solutions that are replicable throughout Alaska and other Arctic regions. This NOTA is intended to implement the first two phases of the RACEE Competition: Phase 1 will designate qualified Alaskan communities that pledge to reduce energy use as Community Efficiency Champions . These Champions will gain access to a peer network and become qualified to apply for Phase 2, which will provide Technical Assistance to selected Community Efficiency Champions. Applicants that become designated as Community Efficiency Champions will be expected to actively share information, best practices and lessons learned with their peers related to their energy efficiency plans and actions through reporting to DOE and Peer Networks.The full NOTA is posted on the EERE Exchange website at https://eere-exchange.energy.gov. Applications must be submitted through the EERE Exchange website to be considered for award. The applicant must first register and create an account on the EERE Exchange website. A User Guide for EERE Exchange can be found on the EERE website http://eere-exchange.energy.gov/Manuals.aspx after logging in to the system. Information on where to submit questions regarding the content of the NOTA and where to submit questions regarding submission of applications is found in the full NOTA posted on the EERE Exchange website.

$1 – $2

rolling

energyclean energy

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

Notice of Withdrawal and Reissue for Notice of Funding Opportunity for Projects Located Off the Northeast Corridor for the Fiscal Year 2024 Federal-State Partnership for Intercity Passenger Rail Program

open

Transportation Department

On October 2, 2024, FRA published a Notice of Funding Opportunity (NOFO) in the Federal Register announcing the availability of funding and procedures to obtain grant funding for eligible projects located off the Northeast Corridor for the Fiscal Year (FY) 2024 Federal-State Partnership for Intercity Passenger Rail Program (FSP- National). The full text of the October 2, 2024, NOFO can be found at www.Grants.gov using the funding opportunity ID FR-FSP-24-003. In order to comply with subsequent Executive Orders and to incorporate additional funding, FRA is withdrawing the full text of the October 2, 2024, notice and re-issuing a notice for FSP-National. The full text of the reissued NOFO can be found using the funding opportunity ID FR-FSP- 23-004. The total funding available for awards under the reissued NOFO is up to $5,070,784,989.

See notice

general

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

Notice of Withdrawal of Guidance Circular 4704.1A

open

Transportation Department

By this notice, the Federal Transit Administration (FTA) withdraws guidance document Circular 4704.1A, Equal Employment Opportunity (EEO) Requirements and Guidelines for Federal Transit Administration Recipients.

See notice

public transit

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

Notice of Withdrawal of Guidance Circular 4704.1A

open

Transportation Department

See notice

general

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

Notification of Rescission of the 2022 Interpretation of Section 188 of the Workforce Innovation and Opportunity Act

open

Labor Department

This notice rescinds guidance that defines the term "sex" for purposes of the Department of Labor's anti-discrimination provisions of its workforce funding and development programs. Specifically, the guidance that is the subject of this notice construed the term "because of . . . sex" to include transgender status and gender identity, based on the Supreme Court case Bostock v. Clayton County. The Department of Labor now rescinds this guidance because later court cases found that the term "sex", as it is used in the context of education funding in Title IX, does not include transgender status or gender identity, and that the holding in Bostock v. Clayton County, which was about Title VII, does not apply to Title IX. This rule is effective immediately and rescinds the former guidance in its entirety.

See notice

Educationinnovationworkforce

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

Notification of Withdrawal of Fair Housing and Equal Opportunity Guidance Documents

open

Housing and Urban Development Department

This notice informs the public that the Office of Fair Housing and Equal Opportunity (FHEO) has withdrawn the guidance documents identified below.

See notice

Housing

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

Notion for Nonprofits

open

Notion (via TechSoup)

50% off Notion Plus plus up to 4 hours of pro bono support for nonprofits to build wikis, docs, and project tools.

Up to $2K

Rolling

technologycapacity_building

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

Nova Scotia Arts Council (Arts Nova Scotia)

open

Arts Nova Scotia

Provides grants to artists and arts organizations in Nova Scotia for creation, professional development, and arts presentation.

$1K – $75K

Rolling

artsculture

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

Nova Scotia Communities, Culture, Tourism and Heritage Grants

open

Government of Nova Scotia

Grants for community development, cultural programs, heritage preservation, and tourism development across Nova Scotia.

$2K – $200K

Rolling

communitycultureheritage+1

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

Nova Scotia Innovation Hub Grants

open

Innovacorp / Nova Scotia Innovation Hub

Innovacorp supports early-stage technology companies in Nova Scotia through grants, investment, and acceleration programs.

$10K – $500K

Rolling

innovationtechnologystartups

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

Novant Health Community Investment Grants

open

Novant Health

Invests in community health improvement programs addressing social determinants of health, health equity, and access to care in the Carolinas and Virginia.

$5K – $500K

Rolling

social determinantshealth equityaccess to care+1

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

Novel Antibody-drug Conjugates for Gamma-Delta T-cell Cancers

open

NCI - National Cancer Institute

Project Summary Gamma-delta T-cell leukemias and lymphomas (GD T-cell cancers), affect ~1000 patients in the United States each year. Patients with GD T-cell cancers respond poorly to chemotherapies, with some patients experiencing a median survival of only 10 to 15 months. Significant challenges in improving survival for these patients are our poor understanding of the genomic mutations that drive GD T-cell cancers and our inability to selectively kill the GD T-cell cancer cells without harming the normal cells. Recent studies performed by multiple groups including ours have identified genomic mutations in critical signaling pathways that converge on the oncogene MYC. MYC is required for cell proliferation and survival in normal cells and increased MYC activity has been linked to the development of multiple solid cancers. Thus, we surmise that the mutations observed in GD T-cell cancers lead to an overactive MYC signaling which may be driving tumorigenesis in GD T-cell cancers. In addition, we postulate that selective inhibition of MYC activity in GD T-cell cancers will kill the cancer cells without harming the normal cells. For Aim 1, we propose to establish a mechanistic link between the genomic alterations observed in GD T-cell cancers and MYC-driven oncogenesis. We will engineer the mutations in normal cells and quantify how these changes lead to increased MYC activity leading to increased cell proliferation that ultimately leads to cancer. To selectively deliver drugs to block MYC activity in GD T-cell cancers, we developed an antibody that targets the GD T-cell receptor, which is only expressed in GD T-cell cancers and normal GD T cells. We coupled the antibody with drugs that block MYC activity and demonstrated that the antibody-drug conjugate (anti-GD ADC) selectively blocks MYC, leading to the death of cancer cells and normal GD T cells. We previously used similar methods to generate ADC to target other T-cell cancers and the ADC is scheduled to enter a phase 1 clinical trial (Nichakawade et al., Nature 2024). As normal GD T cells are a minor percentage (~5%) of immune cells, their loss is expected to be well tolerated in patients. For Aim 2, we will test the anti-GD ADCs in mouse models that closely resemble the human GD T-cell cancers. However, as such mouse models are currently unavailable, we will implant patient-derived and cell line-derived GD T-cell cancers in mice to closely replicate the diverse phenotypes and genomic profiles of GD T-cell cancers observed in patients. We will then test the safety and efficacy of the anti-GD ADCs in our mouse models. Lastly, most cancers treated with ADCs tend to develop resistance leading to cancer relapse. Thus, for Aim 3, we will identify possible resistance mechanisms that may develop in cancer cells to our anti-GD ADCs. We will then generate methods to counter the resistance and test the methods in our mouse models. Our studies aim to establish the mechanism by which normal GD T cells turn into cancer cells. In addition, the studies will provide the pre-clinical validation required to initiate a clinical trial of anti-GD ADCs and may improve the survival of patients with GD T-cell cancers.

Up to $645K

2031-04-30

health research

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

Novel Approaches for Gestational E-Cigarette Vaping-Induced Neuronal Adaptations

open

NIEHS - National Institute of Environmental Health Sciences

PROJECT SUMMARY Electronic cigarette (e-cig) use during pregnancy has become a major health concern in recent years and is perpetuated by the perception that e-cigs are less harmful than traditional combustible cigarettes. Recent estimates show 7% of women use e-cigs in pregnancy, and 45% view them as less harmful and may help them quit or reduce combustible cigarettes in pregnancy. An extensive knowledge gap persists regarding their health impact when aerosolized, especially during pregnancy. Using our well-established pregnant rat model, we obtained preliminary data utilizing a state-of-the-art e-cig system with a commercial e-cig unit and atomizer that offered a translational inhalation delivery and generated vapor profiles directly comparable to human vaping. Our preliminary data demonstrated that a cardinal outcome of e-cig use was a significant fetal and neonatal growth deficit. Concomitant with growth restriction, our exciting preliminary data provides direct evidence that e-cig vaping significantly alters developmental brain hippocampal mTOR system. As a critical node, mTOR regulates essential brain metabolic activities, including protein synthesis and autophagy. Interestingly, our new preliminary data indicate that these mTORC1 and mTORC2 signaling adaptations were accompanied by altered fetal hippocampal dendritic morphology and hippocampal-dependent long term memory deficits. We subsequently generated critical preliminary data that demonstrated that optimizing mTORC1/C2 activity via in vivo administration of the 3rd gen mTORC1/C2 blocker (RapaLink-1) concomitant with e-cig aerosol exposure reversed specific e-cig-induced fetal developmental phenotypes. Thus, we hypothesize that the mTOR system plays a central role in e-cig induced alterations in fetal brain hippocampal adaptations. To test this hypothesis, we will (1) seek to answer fundamental questions about the impact of e-cig aerosol exposure on hippocampal mTORC1/C2 system using novel mechanistic in vivo studies, (2) assess the role of mTOR in e-cig-induced fetal brain hippocampal developmental adaptations using morphometric, stereological and behavioral approaches, and (3) identify e-cig-induced protein signal propagation pathways leading to activation of mTOR and signal propagation downstream of mTORC1/C2 utilizing mass spectrometry- based phosphoproteomics followed by stochastic optimization and reinforcement learning algorithms. We will then compare and interpret the signature pathways impacted by e-cig vaping with and without mTOR blocker using machine learning models. Upon successful completion of these aims, we will have comprehensively characterized the mTOR signaling cascade as it transduces cues from e-cig vaping into molecular action, enabling the identification of potential strategies to mitigate e-cig-induced neurodevelopmental deficits in the hippocampus. The proposed studies develop a strong etiological framework and directly address a “major research area” of developmental impacts under Theme One of NIEHS Strategic Plan 2018-2023, titled “Advancing Environmental Health Sciences”.

Up to $2.1M

2030-05-31

health research

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

Novel Approaches to Advance Precision Aging and Cognitive Health

upcoming

National Institutes of Health

The National Institute on Aging (NIA) intends to publish a Notice of Funding Opportunity (NOFO) to solicit applications that develop or incorporate novel, cutting-edge study designs/methods/analytic approaches through the use of machine learning, artificial intelligence, and adaptive designs to allow the discovery of health/function profiles at the level of the individual and that could lead to the implementation of personalized prevention plans/interventions for cognitive/brain health in older adults. The initiative would allow for both basic research in animal models, as well as the development of profiles for humans, which would span levels of analysis from cellular to societal. Applications are not being solicited at this time. Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. This NOFO will utilize the R01 activity code. Investigators with expertise and insights into this area of aging research are encouraged to begin to consider applying for this new NOFO.

2026-10-06

Health

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

Novel Approaches to Advance Precision Aging and Cognitive Health

upcoming

National Institutes of Health

The National Institute on Aging (NIA) intends to publish a Notice of Funding Opportunity (NOFO) to solicit applications that develop or incorporate novel, cutting-edge study designs/methods/analytic approaches through the use of machine learning, artificial intelligence, and adaptive designs to allow the discovery of health/function profiles at the level of the individual and that could lead to the implementation of personalized prevention plans/interventions for cognitive/brain health in older adults. The initiative would allow for both basic research in animal models, as well as the development of profiles for humans, which would span levels of analysis from cellular to societal. Applications are not being solicited at this time. Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. This NOFO will utilize the R01 activity code. Investigators with expertise and insights into this area of aging research are encouraged to begin to consider applying for this new NOFO.

2026-10-06

Healthhealthcare

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

Novel Approaches to Enhance Animal Stem Cell Research (R21)

open

National Institutes of Health

The purpose of this funding opportunity announcement (FOA) is to encourage the submission of applications for research to enhance animal stem cells as model biological systems. Innovative approaches to isolate, characterize and identify toti-potent and multi-potent stem cells from nonhuman biomedical research animal models, as well as to generate reagents and techniques to characterize and separate those stem cells from other cell types is encouraged. Studies involving human subjects are not allowed under this FOA. Because the nature and scope of the proposed research may vary from application to application, it is anticipated that the size and duration of each award may also vary. The total amount awarded and the number of awards will depend upon the numbers, quality, duration, and costs of the applications received. Mechanism of Support. This FOA will use the NIH Exploratory/Developmental (R21) grant mechanism and runs in parallel with a FOA of identical scientific scope, PA-07-303, that solicits applications under the R01 grant mechanism. Funds Available and Anticipated Number of Awards. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. Budget and Project Period: The total project period for an application submitted in response to this funding opportunity may not exceed two years. Direct costs are limited to $275,000 over an R21 two-year period, with no more than $200,000 in direct costs allowed in any single year.The R21 is not renewable. Eligible Organizations: Public/State Controlled Institution of Higher Education; Private Institution of Higher Education; Hispanic-serving Institution; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); Alaska Native and Native Hawaiian Serving Institutions; Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education); Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education); Non-domestic (non-U.S.) Entity (Foreign Organization); Small Business; For-Profit Organization (Other than Small Business).

Up to $200K

rolling

Education

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

Novel approaches to predict strength and breadth of influenza vaccine response

open

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Influenza vaccines remain the most cost-effective tool for reducing infection and disease burden. However, despite decades of research and development, the protection they provide is often suboptimal. A key challenge is the wide variability in vaccine induced immune responses among individuals, which is poorly understood. Addressing this knowledge gap is crucial for improving vaccine efficacy and vaccination strategies. Predictive modeling, with its demonstrated success in advancing medical research and public health, holds significant promise in this regard. By harnessing predictive models, we can tailor vaccination strategies to individuals, optimizing protection and improving outcomes. Current predictive models, however, suffer from critical limitations. Most rely solely on static, pre- vaccination data and focus narrowly on antibody responses to a single vaccine component (in current vaccines, these are H3N2, H1N1 and one or two of the B lineages). Existing models do not account for the dynamic nature of the immune system or the role of heterologous, non-vaccine-specific antibody responses, reducing their accuracy and practical utility. These shortcomings hinder the development of more comprehensive, adaptable models for predicting vaccine efficacy across diverse populations and viral strains. This project aims to overcome these limitations by developing and validating advanced predictive models for influenza vaccine responses. Our approach integrates systematically collected, longitudinal data with state-of-the-art statistical and machine-learning methods. Specifically, we will: 1. Develop predictive models that incorporate long-term antibody response trajectories and heterolo- gous strain data to improve predictions for vaccine strain responses. 2. Expand the scope of these models to predict heterologous breadth and overall antibody responses, offering a more complete understanding of vaccine-elicited immunity. 3. Generate and analyze high-throughput antibody landscape data to further refine and enhance our predictive models. By combining these innovations, we aim to establish a new framework for individualized vaccine re- sponse prediction. This framework will significantly improve upon existing models, enabling tailored vac- cination strategies designed to optimize protection for each individual. Ultimately, this work will provide a robust scientific foundation for guiding future influenza vaccination efforts, contributing to better public health outcomes worldwide.

Up to $806K

2031-04-30

health research

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

Novel approaches to support therapeutic development in ultra-rare cancers

upcoming

Food and Drug Administration

The purpose of this program is to support new approaches that can be applied to facilitate therapeutic development in ultra-rare pediatric and adult cancers, including molecularly-defined subsets of more common cancers.  Specific areas of interest include, but are not limited to, the following examples:• Development of infrastructure for a coordination network and data repository for patient-level data across institutions and internationally to support drug development and regulatory decision-making for one or more ultra-rare cancers.• Investigations to explore opportunities to develop and validate early clinical endpoints and other novel efficacy endpoints for evaluation of treatments for ultra-rare cancers.• Development and implementation of a collaborative multi-stakeholder effort to support generation and use of real-world data leveraging a registry framework for use in development of new therapies for pediatric patients with diffuse midline glioma (DMG) (including diffuse intrinsic pontine glioma, DIPG). • Innovative approaches to identify new biologically-driven opportunities for clinical development of previously approved drugs or biologics (hereafter referred to as drugs), including drugs for which development has been discontinued, in ultra-rare cancers.• Research to develop novel approaches to preserve the availability of drugs for which commercial developers have discontinued adult development that have strong potential in ultra-rare cancers but lack financial incentives for commercial development• Development of methods to incorporate use of telemedicine and/or pragmatic trial design elements (e.g., collecting laboratory and/or imaging data from local facilities) for patient assessments to facilitate enrollment of patients with ultra-rare cancers• Development of nanoparticle-based delivery approaches for therapeutic nucleic acids targeting onco-fusion transcription factors in metastatic tumor animal models using targeted bioPROTAC degradation or genomic editing strategies. Successful efforts should demonstrate effective delivery and expression in-vivo to tumor cells, and downregulation of the target transcription factor protein while minimizing off-target effects and limiting sequestration of the nanoparticle by the liver, spleen, and lungs.• Research to exhaustively characterize the plasma-membrane protein expression (surfaceome) of an ultra-rare cancer and the presumed healthy tissue of origin, as well as the resident-tissue stem cells, by single-cell transcriptomics and proteomics. These studies, and available correlative database analyses, should be designed to identify possible combinatorial signatures of plasma membrane proteins unique to the ultra-rare tumor. Tumors of interest include Sclerosing epithelioid fibrosarcoma and atypical teratoid rhabdoid tumors (ATRT).

Rolling

Agricultureconsumer_protectionfood_and_nutrition

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

Novel approaches to support therapeutic development in ultra-rare cancers

upcoming

Food and Drug Administration

Novel approaches to support therapeutic development in ultra-rare cancers

Rolling

general

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

Novel Artificial Intelligence approaches to distinguish allergenic from non-allergenic proteins

open

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT Allergic diseases have increased dramatically to become the most common human disorders in developed countries. Despite improved clinical diagnosis and management, they are the leading cause of work and school absences. The prevalence of food allergy is rising for unclear reasons, with prevalence estimates in the developed countries around 10%. Peanut allergy affects 1–2% of the population in Westernized nations and is a leading cause of food-induced anaphylaxis. Specifying and maintaining elimination diets places a significant burden on patients, families and healthcare systems. The possibility of anaphylactic responses by sensitized individuals complicates food manufacturing, as the products should be free of unmarked allergy triggers, including peanuts, tree nuts, wheat, soy, fish, shellfish, eggs and milk. Thus, there is an unmet need to identify allergen features and find proteins which could cause cross-reactions in sensitive individuals among the vast number of proteins now catalogued in proteome databases. A first version of a novel machine learning (ML) tool, AllergenAI, which used only amino acid sequences in three allergen protein databases, SDAP 2.0, COMPARE and AlgPred, achieved robust results. To further improve this ML model, we will use Alphafold-2 to model all proteins in these three databases and incorporate the 3D structural information into AllergenAI (Aim1). The predictive abilities of AllergenAI will be experimentally assessed in Aim2, by analyzing the features scores for well-studied vicilin allergens, which are among the most common allergens (with over 20 entries in the Structural Database of Allergenic Proteins (SDAP), including the major allergen Ara h 1 of peanuts and its homologues in tree nuts, legumes and cotton). The program’s ability to distinguish homologues in the very broad vicilin protein family that could cause cross-reactions with IgE in allergic patient sera will be tested. The weight parameters of AllergenAI will be fine-tuned by using a Large Language Model (LLM) ESM-2 in Aim 3. The optimized AllergenAI will be benchmarked by comparison to other prediction methods for allergenic proteins that are based on sequence alone. We hypothesize that artificial intelligence (AI) technologies that made dramatic improvements in recent years will clarify the problem of “what makes a protein allergenic”. The application of AI technology to allergen research is novel. Our combined experimental and computational approach will yield a powerful new method to identify potential allergenic characteristics in new proteins and help design better immunotherapies for allergenic diseases. The source code for the optimized AllergenAI model, documentation for use and example input files will be made available from our SDAP 2.0 website, which is used extensively by researchers and clinicians throughout the world.

Up to $429K

2031-01-31

health research

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

Novel BDNF-TrkB enhancing therapeutic to treat traumatic brain injury

open

NINDS - National Institute of Neurological Disorders and Stroke

Traumatic brain injury (TBI) affects an estimated 1.7 million civilians in the US each year at an estimated cost of $76.5 billion in the U.S. alone. Due to the complex nature of the pathophysiological events there remains an unmet medical need for therapeutics that prevent secondary neuronal damage. Brain-derived neurotrophic factor (BDNF) through activation of its high affinity receptor, TrkB, is a key player in promoting learning, and therapeutic strategies to enhance BDNF signaling after TBI facilitate recovery. PSD-95 is a TrkB associated synaptic scaffolding protein required for BDNF-induced signaling. We developed a high affinity and proteolytic stable macrocyclic compound, D-Syn3, targeting the PDZ3 domain of PSD-95. D- Syn3 increases the recruitment of PSD-95 to TrkB to augment pro-survival BDNF signaling. In a series of preclinical studies in TBI rodent models, we found that D-Syn3 rapidly penetrates the CNS to reduce post- injury neuronal death, cis P-tau, gliosis and demyelination, to improve long-term neurobehavioral outcomes. Taking advantage of the distinct pathology in the Controlled Cortical Impact (CCI) and repetitive moderate closed head injury (rmCHI) models, we will fully evaluate the efficacy of our novel BDNF-targeted therapy, which has demonstrated promise in both models. We will determine the efficacy of D-Syn3 to mitigate injury and behavioral deficits using two complementary TBI models: A contusive control cortical impact (CCI) model (Aim 1) and a concussive closed head injury (CHI) model (Aim 2). For each model, we will identify the optimal dosing regimen of D-Syn3 to mitigate pathology. Using this optimal regimen we will evaluate efficacy to prevent impairment in learning/memory, motor function, and depression-like behavior. Given the pilot efficacy of D-Syn3, we anticipate that successful completion of this work will lead to a new therapeutic for TBI.

Up to $254K

2028-04-30

health research

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

Novel biomarkers and mechanisms of Alzheimer's disease

open

NIA - National Institute on Aging

Project Summary / Abstract Alzheimer's disease (AD) is a devastating dementia with enormous societal burden. Despite recent advances in the development of AD biomarkers and anti-A antibodies as disease-targeting therapies, AD remains challenging to treat, highlighting the urgent need for new biomarkers and targets to improve AD diagnosis and treatment. The goal of this project is to perform innovative research to discover glycosylation-based disease processes and identify glyco-biomarkers and targets for improving AD diagnosis, prognosis, and intervention. Glycosylation is the most prevalent and complex form of protein modification which produces a wide variety of glycosylated proteoforms or glycoforms to control many biological processes, including synaptic function and brain homeostasis. The prevalent localization of glycoproteins and glycoforms in extracellular space and cell surface makes them an attractive source of disease biomarkers and drug targets. Recent evidence obtained by our group and others indicates a link between altered protein glycosylation and AD pathogenesis. However, current knowledge of system-wide changes in protein glycoforms and glycan modifications in AD is limited, and the potential impact of aberrant glycosylation on the etiology of AD and biomarker discovery remain underexplored. The proposed project will address the gap in knowledge and test the novel hypothesis that glycoproteostasis dysregulation and glycoform alterations are critically involved in AD development and progression. We have recently established an innovative platform that integrates intact glycopeptide-based quantitative glycoproteomics and systems biology for large-scale, in-depth analysis of protein glycoforms and site-specific glycan modifications in human patient specimens. We will perform experiments using this transformative platform to elucidate brain glycoproteome alterations in AD and uncover disease-associated targets, networks, and pathways. In addition, we will perform proteome-wide glycoform profiling studies of cerebrospinal fluid and blood specimens from AD and control cases to identify glyco-biomarkers reflective of diverse AD pathophysiology at different disease stages for timely diagnosis and monitoring disease progression. Successful completion of the proposed research will generate new insights into AD pathogenic mechanisms, provide novel biomarkers for AD diagnosis and prognosis, and pave the way forward for developing glycosylation-based therapies to combat this devastating disease.

Up to $644K

2031-01-31

health research

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