Grants

Education

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Gut Check: The Impact of Gut Bacteria on Physical Function in Older Adults with and without HIV

NIA - National Institute on Aging

ABSTRACT. Physical function refers to an individual's ability to perform daily tasks and activities and is a crucial aspect of overall health. Maintenance of physical function is the cornerstone of successful aging with declines in physical function associated with increased risk of hospitalization, institutionalization, and premature mortality. We and others have shown that chronic diseases, including HIV, can significantly accentuate the decline of physical function. The gut microbiome plays a pivotal role in the regulation of gut health. Alterations in gut microbial communities (dysbiosis) accompany physiological aging and emerging evidence illustrate links between the gut microbiome and physical function and frailty in older people without HIV. HIV-associated dysbiosis has been reported to be among the strongest disease-associated dysbioses, and associations between the gut microbiome and multiple aging outcomes in PWH have been observed. In a recent study of sedentary older people with and without HIV, we found that HIV serostatus modified the fecal microbiome, such that those with HIV had a unique microbiome with increasing age. Emphasizing the clinical relevance of these findings in a subsequent pilot study, we observed associations between gut bacterial abundance and physical function that differed between older people with and without HIV, highlighting the need to understand these relationships in different disease states. We recently explored associations between frailty and gut microbiome within the MACS/WIHS Combined Cohort Study (MWCCS), a large nationwide, ongoing observational cohort. Differences by age among both men and women with and without HIV were noted; importantly, specific genera were associated with lower or greater odds of frailty, a composite measure indicative of vulnerability with aging. Frailty is a broad syndrome and recognizing gut microbiome relationships to specific measures of physical function will provide greater specificity as to potential mechanisms. Moreover, understanding both bacteria abundance and functional output are needed to properly appreciate the complex relationship between gut bacteria imbalances and physical function. To investigate our central hypothesis that HIV- and age-induced gut dysbiosis is associated with physical function impairments, we will evaluate relationships between fecal bacteria abundance and functional potential with physical function using data collected as part of the MWCCS. We will first evaluate cross-sectional relationships (Aim 1) and then determine if gut microbiome patterns predict changes in physical function over time (Aim 2). The knowledge gained from this well-powered investigation into the gut- physical function axis will promote the development of effective population-specific, strategically designed and cost-effective adjunct microbiome-based therapies to prevent or reverse physical function impairments among older adults, including those with HIV who experience age-associated decline in physical function at an earlier age.

Up to $156K

2028-03-31

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Gut Microbial Protein Metabolism in Food Allergy and Oral Immunotherapy Efficacy

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary/Abstract Food allergies are common and life-threatening pediatric conditions, predominantly triggered by specific protein motifs in foods, such as Ara h proteins in peanuts (e.g., Ara h 2). Allergen-specific oral immunotherapy (OIT), in which patients are exposed to increasing doses of allergens to desensitize their immune systems, has emerged as a promising treatment for food allergies. However, OIT induces sustained remission in only a fraction of food- allergic patients, and the factors contributing to treatment response remain elusive. My postdoctoral studies have identified strong relationships between the gut microbiome and the response to peanut OIT (POIT) in the IMPACT clinical trial. We found that children who did not respond to POIT have a distinct gut microbiome composition that is significantly enriched in the Xaa-Xaa-proline tripeptidyl-peptidase (ptpA) gene, which encodes a hydrolase that cleaves tripeptides with a proline residue at the third position from the N-terminal of polypeptides. The copy number of the ptpA gene positively correlates with peanut allergen component (Ara h 2) -specific IgE levels. Additionally, we showed that the gut microbiome can metabolize one of the most proteolysis- resistant allergenic peanut proteins, Ara h 2. The microbiome of those who failed to achieve POIT-induced remission exhibited a significantly increased capacity to metabolize Ara h 2 compared to those who achieved remission. This suggests that enhanced microbial metabolism of allergenic peanut proteins may be associated with POIT failure. This proposal comprises three interlinked but independent investigations. Study 1 will test whether interindividual response to POIT is associated with the gut microbial peanut protein metabolism and specific peanut proteins reaching the lower gastrointestinal tract. Study 1 will also investigate the molecular mechanisms by which the human gut microbiome metabolizes allergenic peanut proteins and aims to isolate specific gut microorganisms with peanut protein metabolism capacity. Study 2 will investigate the role of the gut microbial ptpA gene, which is enriched in POIT non-responders, in peanut protein metabolism. Study 3 will develop engineered probiotic bacteria to produce individual peanut Ara h proteins, offering a novel in situ immunotherapeutic production and delivery approach. Leveraging targeted proteomics, next-generation sequencing, in vitro bioreactor arrays, gnotobiotic mouse models, and clinical samples from the IMPACT clinical trial, this proposal aims to identify the molecular mechanisms by which the human gut microbiome affects POIT efficacy. This research, which bridges the gap between gut microbial protein metabolism and POIT efficacy, has the potential to enhance the effectiveness of OITs, bringing us closer to tailored treatments for food-allergic patients.

Up to $467K

2031-01-31

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Gut microbiome manipulation to improve efficacy and durability of anti-TNF treatments for inflammatory bowel disease

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Project Summary/Abstract: This proposal addresses the significant challenge of limited treatment options in inflammatory bowel disease (IBD) and the loss of response to therapies that were previously effective. The long-term objective is to improve the clinical management of IBD by enhancing the initial response to therapy and extending the duration of remission, therein reducing the need for alternative medications or surgical interventions. Specifically, our study will investigate the role of the gut microbiome in modulating the initial effectiveness of anti-TNF therapies, as well as its ability to prevent anti-drug antibody (ADA) development, a common cause of subsequent treatment failure. In Aim 1, we will determine whether the response to anti-TNF therapy induction can be improved by transplanting the gut microbiome of known treatment responders into recipients planning to undergo therapy. Germ-free mice will be colonized with fecal inocula from human patients previously determined to have either responded, or not responded, to anti-TNF therapy. Following the development of intestinal inflammation, the mice will be treated with anti-TNF injections and evaluated for differential treatment response. To assess the robustness of our findings, we will utilize two germ-free IBD mouse models which have been previously demonstrated to be microbiome responsive: the IL-10 knockout and the adoptive T-cell transfer models. Furthermore, emerging studies have shown that exposure to different classes of antibiotics can alter the risk of ADA development among IBD patients treated with anti-TNF therapies. Therefore, our second Aim will be to evaluate if the durability of anti-TNF treatment can be enhanced by the ingestion of microbial communities shaped by antibiotic use. To parallel a future clinical scenario in which microbes may be delivered prophylactically, we will gavage conventional C57Bl/6 mice with microbiomes from mice that have been given various antibiotics. Recipient mice will then be treated with an anti-TNF and subsequently assessed for ADA development. The proposed research will integrate fecal metagenomic, transcriptomic, and metabolomic data to elucidate the molecular basis of the microbiome’s effects. The project endeavors to improve therapeutic strategies for IBD by optimizing the use of anti TNF-inhibitors which are already widely available, therefore offering a scalable approach that can be quickly implemented to address current challenges in IBD care, to guide antibiotic treatment decisions, and to help explain the heterogeneity of anti-TNF response, which has long been clinically recognized but incompletely understood.

Up to $773K

2031-02-28

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Gut Microbiome Steroid Hormone Metabolism in Inflammatory Disease

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ABSTRACT Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation with unpredictable flares that significantly impair patient quality of life. The gut microbiome plays a central role in IBD pathogenesis, yet specific mechanisms linking gut bacteria to inflammatory processes remain poorly defined. Glucocorticoids function as critical mediators in IBD both as endogenously produced anti-inflammatory molecules that help maintain mucosal homeostasis and as exogenously administered therapeutic agents for managing acute flares. This proposal investigates a novel bacterial pathway that enzymatically converts active glucocorticoids to inactive metabolites in the gut microbiome. Our preliminary data demonstrate that steroid- metabolizing bacterial enzymes are significantly enriched in IBD patient microbiomes compared to healthy controls, suggesting a potential contribution to disease pathogenesis. We hypothesize that microbial inactivation of glucocorticoids disrupts anti-inflammatory signaling and exacerbates intestinal inflammation. To test this hypothesis, we will employ gnotobiotic mouse models with genetically defined bacterial strains that either possess or lack glucocorticoid-metabolizing capability, evaluating their impact in the presence or absence of therapeutic glucocorticoid treatment. This exploratory research aims to investigate a potential novel mechanistic link between microbial modulation of host endocrine signaling and inflammation, which may ultimately inform the development of microbiome-based diagnostics and therapeutic approaches for inflammatory digestive diseases.

Up to $244K

2028-04-30

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Gut Microbiota-Derived 3-PPA as a Metabolic Modulator of Beige Adipogenesis and Energy Homeostasis

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Project Summary/Abstract Obesity and metabolic disorders are leading causes of morbidity worldwide, driven in part by impaired thermogenic fat function and disrupted energy homeostasis. Beige adipocytes are inducible thermogenic fat cells within white adipose depots that play a critical role in regulating systemic metabolism by increasing energy expenditure and improving glucose and insulin homeostasis. Enhancing beige fat function represents a promising strategy for mitigating metabolic disease, yet the regulatory pathways governing beige adipogenesis, particularly in obesity, remain incompletely understood. Recent evidence from our group identifies 3- phenylpropionic acid (3-PPA), a gut microbiota-derived metabolite, as a key endogenous factor that promotes beige adipocyte formation and improves metabolic outcomes in vivo. Our preliminary data demonstrate that 3- PPA engages an immune–adipose axis involving GPR40 activation in macrophages, CXCL13 secretion, and T follicular helper (Tfh) cell recruitment. However, the broader physiological significance and therapeutic potential of this signaling axis in the context of obesity and insulin resistance remain unknown. We hypothesize that 3- PPA enhances beige adipogenesis and mitigates metabolic dysfunction through coordinated microbiota–immune–adipose interactions. To test this, we will: (1) characterize the role of GPR40-mediated signaling in macrophages during 3-PPA–induced metabolic remodeling; (2) define how CXCL13-Tfh cell interactions influence beige adipogenesis in obesity; and (3) assess the efficacy of 3-PPA-based interventions in mouse models of diet-induced obesity and metabolic disease. This research integrates metabolic physiology, immunometabolism, and microbiota-derived signaling to uncover disease-relevant mechanisms regulating thermogenic fat function. Findings may provide the foundation for novel microbiota-targeted therapies for obesity and metabolic disorders.

Up to $787K

2031-04-30

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Guts, Resilience, Ingenuity, and Tenacity (GRIT)

Somali Community Services of Seattle

If, as research suggests, youth gun violence (such as that in Rainier Beach) is at least partly due to despair and pain, then why not address the causes? Our Somali youth experience great despair - akin to the typical young aduurance, living alone) to which are added an empty cupboard, eviction, unemployment, lack of a high school diploma, etc. Just as explorers of outer space have intensive training, ongoing communication and detailed user manuals outlining their options, resources, and support available in unfamiliar situations, so should our youth have access to training and other aids to navigate their strange new world. Operation GRIT offers 30 youth (14 to 24 years old) intensive training (60 hours) on essential self-care practices needed for overall well-being, and a violence-free life; related discussion groups (60 hours); a 60-hour media and podcasting workshop; and 3 1-hour podcasts so GRIT grads can share their wellness wisdom with their peers.

Up to $50K

EducationHealthworkforce+1

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Gutter/Siding Repair on VFW Building

Rainier Beach Community Club

This project repairs the gutter and siding on the southwest corner of the VFW building located at 6038 S Pilgrim St Seattle Wa 98118. The anticipated project end date is July 30, 2021.

Up to $4K

infrastructure

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GWAS-Based Neurovascular Etiology of Migraine and its Associated Risk of Ischemic Stroke

NINDS - National Institute of Neurological Disorders and Stroke

Migraine is a unique and severe form of headache. It is also common, experienced by up to 30% of women with age-related prevalence 2-3x higher than men, and is a leading cause of disability worldwide. Migraine has a broadly neurovascular pathophysiology that may be treated by recently introduced drugs targeting the calcitonin gene-related peptide (CGRP), the CGRP receptor, or the serotonin receptor (HTRA11F). However, these drugs remain ineffective or contraindicated for many migraine sufferers, highlighting the need for additional therapeutics. Disability due to migraine is compounded by an approximate 1.5-fold elevated risk of ischemic stroke that is further elevated among individuals who experience migraine with aura, a form of migraine typically experienced as a reversible visual disturbance preceding the headache. The cause of such strokes is unknown but may involve intrinsic properties of the vasculature and/or microembolism. Both the identification of critically needed new therapeutic targets and a better understanding of the elevated ischemic stroke risk would be advanced by addressing gaps in knowledge about the pathophysiology of migraine susceptibility. The International Headache Genetics Consortium (IHGC) recently (in 2022) reported a new genome-wide association study (GWAS) that identifies 123 susceptibility loci for migraine with a strong aggregate signal related to vascular biology and also evidence of neurological functions. Here, we propose computational and experimental approaches to investigate specific causal mechanisms of migraine related to the genetic signals in this GWAS as well as in a proposed new genetic analysis of ischemic stroke among individuals with migraine. In Specific Aim 1, we will perform the new GWAS of ischemic stroke among individuals with migraine using existing large cohorts and biobanks to identify key risk loci and therefore genes underlying these events. In Specific Aim 2, we will investigate the impact of loci in the IHGC 2022 migraine and Specific Aim 1 GWAS’s on patterns of coordinately regulated, cell-specific transcription (“programs”) using two approaches: 1) Newly available computational methods that leverage public single cell expression data, and 2) a recently proven experimental strategy that perturbs the RNA expression at the GWAS loci in vascular endothelial and smooth muscle cells. Specific Aim 3, we would use computational and experimental approaches first to investigate overlap of targets of recent CGRP and ditan therapies with inferred transcriptional programs or biological pathways of migraine and strokes to better understand the mechanisms of these new drugs. Then, we will use similar methods to investigate whether existing drugs may be candidates for reducing the burden of migraine or stroke through repurposing. Thus, we propose three independent but complementary Specific Aims to advance mechanistic understanding of the pathophysiology of migraine and the associated risk of ischemic stroke, toward elucidating the action of existing treatments and potentially identifying novel therapeutic approaches.

Up to $746K

2031-03-31

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H-E-B Tournament of Champions

H-E-B

Major community giving program funding education, hunger relief, and community development in Texas.

$10K – $500K

Educationhunger reliefcommunity development

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H342--RFQ Life Safety Statement of Conditions Inspection Services

VETERANS AFFAIRS, DEPARTMENT OF.VETERANS AFFAIRS, DEPARTMENT OF.249-NETWORK CONTRACT OFFICE 9 (36C249)

H342--RFQ Life Safety Statement of Conditions Inspection Services

general

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H391--Annual Fuel Oil Tank Tightness Testing

VETERANS AFFAIRS, DEPARTMENT OF.VETERANS AFFAIRS, DEPARTMENT OF.247-NETWORK CONTRACT OFFICE 7 (36C247)

H391--Annual Fuel Oil Tank Tightness Testing

general

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

Habitat and Population Evaluation

Fish and Wildlife Service

Since 1988 the Habitat and Population Evaluation Teams in Regions 3 and 6 have collected data on condition and duck use of a static sample of over 6,000 wetlands. This is one of the largest on longest-term data sets in the world of weather, wetland condition and wildlife use. The proposed project will provide financial assistance for a graduate student investigating the effects of trees, terrain relief, vegetation cover class, watershed land use, weather and other factors on annual duck density. The results of this analysis will inform habitat management and acquisition decisions in the U.S. prairie pothole region of Iowa, Minnesota, North Dakota, and South Dakota.

Up to $33K

sciencetechnology

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Habitat Assessment for Re-establishing Extirpated Cascades Frog in Lassen Volcanic National Park

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 financial assistance for the following project activities without competition: Cooperative Agreement P17AC01723 with Washington State University, a partner under the Pacific Northwest Cooperative Ecosystem Studies Unit, for the project titled "Habitat Assessment for Re-establishing Extirpated Cascades Frog in Lassen Volcanic National Park."

Up to $29K

natural resources

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Habitat Enhancement by Youth Crews

Fish and Wildlife Service

The purpose of this federal assistance is to restore and manage native habitat on federal lands, adjacent non-federal lands and areas of interest in support of the USFWS youth program located throughout the states of Wisconsin, Michigan, Iowa, Illinois and Minnesota. To accomplish this goal, the recipient intends to provide youth crews to restore both native grassland, oak savannas, wetland, riparian, and forest habitat; in addition to other stewardship services such as invasive species removal, hazardous fuel reduction, fence line removal, tree cutting and or planting, habitat mapping and installation of parking lots and gates to provide for and direct public access. These actions will help conserve and protect native plants and animals for not only their benefit, but also for the public good derived from such conservation efforts. Through the activities provided through this Agreement, the Service will be better able to manage grassland, wetland, riparian, forest and oak savanna habitat. Many of these activities will be projects completed by working side-by-side with Service staff in the field.

$25K – $280K

Education

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Habitat for Humanity — Veterans Build

veteran housinghome constructioncommunity build

Habitat for Humanity

Dedicated housing program building and repairing homes for veteran families in partnership with local affiliates.

$25K – $200K

2026-10-15

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

Habitat for Humanity Disaster Response Grants

Habitat for Humanity International

Provides disaster shelter kits, home repair, and long-term rebuilding assistance after natural disasters through trained volunteer teams.

$10K – $250K

disaster responseshelterrebuilding

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

Habitat for Humanity Grant Programs

Habitat for Humanity International

Beyond volunteer home-building, Habitat administers grants for affordable housing, neighborhood revitalization, and disaster recovery programs worldwide.

$25K – $500K

Housingcommunity developmentdisaster recovery

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

Habitat for Humanity International Development Grants

Habitat for Humanity International

Supports housing programs in 70+ countries. Funds construction, microfinance for housing, and community resilience programs.

$50K – $1M

international housingmicrofinancecommunity resilience

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

Habitat for Humanity U.S. Program Grants

Habitat for Humanity International

Supports affordable housing construction, rehabilitation, and community development through 1,100+ local Habitat affiliates across the U.S.

$25K – $500K

affordable housingconstructioncommunity development

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

Habitat for Humanity Veterans Build Program

Habitat for Humanity International

Dedicated program providing home repairs, mortgage-free homes, and community engagement for U.S. military veterans and their families.

$10K – $100K

veterans housinghome repaircommunity engagement

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

Habitat Improvement for the Endangered Mohave Tui Chub (fish) at Mojave National Preserve

National Park Service

A.Project Goals - Historically, Lake Tuendae, which hosts one of the primary populations of Mohave tui chub (fish), had to be dredged every 10 years to remove cattail and aquatic ditchgrass (Ruppia maritime) detritus. This activity leads to substantial tui chub mortality just to maintain its habitat. This requires lengthy Section 7 formal consultation with the US Fish and Wildlife Service. After the last dredging action in 2001, members of the interagency recovery team have been able to postpone the need for dredging by over five years due through conducting annual cattail control actions. However, in the past two years several key participants have retired or been reassigned. As a result, cattail control has been minimal and growth has expanded by over 30 square meters in Lake Tuendae and MC Spring due to the inability of MOJA staff alone to keep up. Thus, to minimize the need for dredging, cattail control needs to continue and transplant of native plants completed to prevent re-establishment of cattails. B.Project Objectives - MOJA staff has identified by completing these three objectives towards the endangered Mohave Tui Chub habitat enhancement in Lake Tuendae, MC Spring, West Pond and Morning Star Mine Lake, should help with their survival rates. a. Objective one, involves obtaining water body dimensions such as depth, width and vegetation cover along with water quality measurements of temperature, dissolved oxygen and total dissolved solids (TDS). Results will be compared with previous data. b. For Objective two, the cattail will be cut with cutters with handles of varying length and a flat bottom boat to access cattail stems for cutting as close to soil level as possible. Cutting will be done monthly and continue monthly during the cooler part of the year, to control any regrowth. Some dead mats of Ruppia spp. will be raked from the water to reduce its extent across open water. c. For Objective three, dig up local stocks of bulrush and Cooper s rush from non-tui chub bearing waters and transplant immediately to cattail infested areas at the water s edge. Follow up visits to cutback cattails from around the transplants will be conducted until the transplants have established. It is anticipated 250 to 300 individuals of each species would be needed to cover the required area. This project should further minimize the need for any future dredging of the habitat that results in mortality of tui chub (fish). The Research Associate (RA) will be able to conduct about half of the tasks independently and the rest with existing MOJA staff.

$20K – $48K

natural resources

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

Habitat Prioritization Connectivity and Fire Risk Analysis Tools

Fish and Wildlife Service

Provide training to the Yreka Fish and Wildlife Office staff on the Environmental Evaluation Modeling System approach to be used for ongoing wildlife management

$20K

natural resources

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

Habitat restoration and management project

Fish and Wildlife Service

conduct and support habitat restoration and management projects at the Tualatin River National Wildlife Refuge Complex (TRNWRC) through the hiring, administration, and execution of year round and seasonal habitat and biological coordinator positions.

$1 – $34K