Grants

NIAID - National Institute of Allergy and Infectious Diseases

To develop a CRISPR-based diagnostic assay for malaria detection.

NSF

This project aims to develop a next-generation, ultrasensitive, and easy-to-use diagnostic platform for detecting nucleic acids – biological molecules that serve as essential markers for diseases and pathogens. The proposed diagnostic device merges cutting-edge advances in nanomaterials, sensor engineering, and gene-editing-inspired detection to allow accurate and rapid identification of nucleic acids without the need for complex laboratory procedures. Unlike conventional approaches that require nucleic acid amplification and trained personnel, this platform enables direct detection at the point of care with performance rivaling gold-standard methods. The anticipated outcomes support the national interest by promoting scientific progress and public health preparedness, with potential applications in clinical diagnostics, environmental monitoring, food safety, and biodefense. This project will also contribute to workforce development through educational integration at multiple levels. Research outcomes will be incorporated into university-level engineering courses and used to develop hands-on learning modules for outreach programs. These activities aim to foster greater engagement in science and engineering fields through learning opportunities and exposure to interdisciplinary research. The goal of this project is to develop a preamplification-free electrochemical nucleic acid testing platform that combines graphene-based redox cycling with CRISPR-Cas enzymatic amplification to achieve attomolar-level sensitivity and high specificity. The research focuses on four core innovations: (1) signal amplification through redox-tagged reporter aptamers confined in a dual-electrode array of graphene microstructures; (2) modulation of redox cycling efficiency through plasma-induced functionalization of graphene to enhance charge transfer kinetics; (3) integration of 3D dual-functional capture electrodes that enable rapid and multimodal signal readout; and (4) demonstration of the platform for virus DNA detection using a CRISPR-Cas12a assay. While the initial focus is on detecting single-stranded DNA, the platform is adaptable to detect RNA targets through modification of the CRISPR assay. The project will advance the understanding of device-material-biomolecule interactions and provide a framework for the development of high-performance, field-deployable biosensors for a broad range of applications. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NINDS - National Institute of Neurological Disorders and Stroke

Friedreich’s ataxia (FRDA) is the most common autosomal recessive ataxia. It is caused by expanded GAA repeats at the first intron of the frataxin (FXN) gene. No effective treatments are available for the disease due to the inherited expanded GAA repeats in the patient’s genome. Thus, there is an urgent need to develop FXN gene-targeted GAA repeat contraction for FRDA treatment. We have recently found that inhibition of histone H3 lysine 9 (H3K9) methylation can induce large GAA repeat contraction in FRDA neural cells and transgenic mice by opening the chromatin and promoting DNA base excision repair (BER) at the FXN gene. We hypothesize that FXN gene-targeted histone demethylation interplays with BER to contract GAA repeats and activate the FXN gene in FRDA. We will test the hypothesis using CRISPR/deadCas9 (dCas9)-mediated FXN gene-targeted histone demethylation to disrupt heterochromatin, induce BER-mediated GAA repeat contraction, activate FXN gene and relieve FRDA phenotypes. This will be achieved by the integrated indispensable expertise of all the PIs through their synergistic team efforts. First, we will determine if CRISPR/dCas9-mediated FXN gene- targeted histone demethylation can alleviate heterochromatinization and induce BER, leading to GAA repeat contraction and relief of FRDA phenotypes. We will determine if FXN gene-targeted histone demethylases KDM4D, KDM6A, and KDM6B can induce BER to contract GAA repeats, relieving FRDA phenotypes in FRDA neural and cardiac cells. Second, we will determine if the human vault nanoparticle-mediated FXN gene-targeted histone demethylation can lead to GAA repeat contraction and relief of FRDA phenotypes. We will encapsulate sgRNA-dCas9-histone demethylases into recombinant vault nanoparticles. We will then test if the vault-mediated histone demethylation can induce GAA repeat contraction via BER, activate the FXN gene, alleviate FRDA phenotypes, and interplay with the function of the blood-brain barrier. Third, we will determine if FXN gene- targeted histone demethylation can lead to cellular differential effects on GAA repeat contraction, FXN gene activation, and relief of FRDA phenotypes via cell-cell interaction. Using a single-cell analysis, we will determine if FXN gene-targeted histone demethylation can cause cellular differential effects on GAA repeat contraction, FXN gene activation, and energy production via cell-cell communication. Fourth, we will determine if FXN gene- targeted dCas9-histone demethylases can coordinate with a nucleosome to demethylate histones on expanded GAA repeats at the FXN gene. We will use molecular dynamics simulation, machine learning, and the AI tool AlphaFold3 to determine the FXN gene-targeted substrate recognition of dCas9-histone demethylases through their interaction with a nucleosome. Our study will reveal the novel mechanisms of FXN gene-targeted GAA repeat contraction, create a bionanoparticle-mediated FXN gene-targeted platform for GAA repeat contraction, and open a new horizon for developing AI-assisted mechanism-based gene therapy for FRDA. Thus, it will fundamentally transform the research and treatment for FRDA and other neurological diseases.

National Endowment for the Humanities

CRISPUS ATTUCKS: REPRESENTING REVOLUTION [THE CHILDREN'S MUSEUM OF INDIANAPOLIS, IN PARTNERSHIP WITH THE CRISPUS ATTUCKS MUSEUM, WILL PRODUCE A NEW EXHIBITION, "CRISPUS ATTUCKS: REPRESENTING REVOLUTION" (WORKING TITLE). THE EXHIBITION WILL EXPLORE THE AMERICAN REVOLUTION THROUGH THE STORY OF CRISPUS ATTUCKS, THE FIRST AMERICAN TO DIE IN THE BOSTON MASSACRE, AND WILL EXAMINE HIS ENDURING LOCAL LEGACY THROUGH INDIANAPOLIS'S HISTORIC CRISPUS ATTUCKS HIGH SCHOOL. FEATURING REAL REVOLUTIONARY WAR ARTIFACTS FROM THE MUSEUM'S COLLECTION AND OBJECTS FROM THE HIGH SCHOOL'S FOUNDING, THE EXHIBITION WILL ENGAGE CHILDREN AND FAMILIES AS WELL AS STUDENTS IN EXPLORING AMERICA'S REVOLUTIONARY VALUES AND HOW AMERICANS CONTINUE TO LIVE OUT LIBERTY, JUSTICE, AND EQUALITY TODAY.]

Cristina Foods, Inc.

Food Beverage and Tobacco Products

NHLBI - National Heart Lung and Blood Institute

Project Summary/Abstract Injury is the most common cause of death in people 46 years of age and younger. Bleeding from injury (trauma-induced hemorrhage) is the second leading cause of injury-associated death and the most common cause of preventable death. Annually, 70-100,000 Americans suffer a preventable death from trauma-induced hemorrhage. These deaths could be prevented were patients to receive timely care (e.g., hemostatic resuscitation and hemorrhage control procedures within two hours of injury) in hospitals that specialize in injury care (e.g., high level trauma centers). These high-level trauma centers have the equipment, blood products, medications, massive transfusion protocols and staff 24 hours a day, 7 days a week to provide hemostatic resuscitation and hemorrhage control procedures. These resources and services are not available at non- specialized hospitals. Management of bleeding requires timely procedures to stop the bleeding as well as medications and blood transfusions to prevent blood from thinning (trauma-induced coagulopathy). Our previous work demonstrated that the most common reason patients were not quickly transferred (retriaged) from non-specialized hospitals to another specialized high-level trauma center was because clinicians did not know who should be retriaged. There are no national retriage guidelines. Our literature review demonstrated only 22 out of 50 states in the United States have any retriage guidelines. Even among states that have retriage guidelines, most guidelines are very vague (e.g., hypotension requiring blood transfusions). This application’s broad, long-term objective is to improve the timeliness of care of trauma-induced hemorrhage. We propose to comperehensively determine who should be quickly retriaged to specialized high-level trauma centers, and determine if state-of-the-art approaches to informing retriage decisions could improve timliness of treatment and reduce death rates. This study’s first specific aim will identify which patients and injuries have the greatest reduction in death rates upon retriage from non-specialized to specialized high-level trauma centers using Causal Graphical Models. The second aim will understand which patient injury and context attributes multi-speciality injury experts prioritize when making retriage choices using Discrete Choice Experiments. The third aim will determine if a protocol providing retriage decision support [PRotocol for OpMTimal reTRiage [PROMTR)] could improve time to treatment and death rates compared to usual care using Discrete Event Simulation. Upon demonstrating efficacy in improved timeliness of treatment and death rates in this simulation study, our future direction will be implementing and evaluating effectiveness of PROMTR in a Hybrid Type II Cluster Randomized Controlled Trial. This line of research has high potential to improve and standardize existing retriage practices, resulting in the reduction of preventable injury-associated death from bleeding.

Tigrean Community Association in Seattle

The Tigreans in Seattle have been disconnected from their families in Ethiopia for over two years due to the unrest and blockage of the region. There is no telephone, electricity, or Internet. Tigreans here are distressed and getting chronic disease like hypertension and mental health disturbances. This project will provide outreach, support, and health resources for Tigreans in Seattle who have lost contact with friends and relatives in Ethiopia. This project will be completed by December 29, 2023.

NIGMS - National Institute of General Medical Sciences

No change from the original submission.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

PROJECT SUMMARY This study aims to understand kidney stone formation by examining interactions between calcium oxalate (CaOx) crystals, bacteria, and host factors, with certain bacterial genes playing crucial roles. Kidney stones are increasingly common, especially among children, and current treatments have remained unchanged since the 1960s, focusing on preventing crystal formation rather than addressing the mechanisms that turn crystals into complex stones. Research has identified bacteria like Enterobacteriaceae in kidney stones, with experiments showing E. coli increases CaOx deposits in mice. The urinary microbiome differs in stone formers compared to healthy individuals, with some bacteria promoting stone formation and others offering protection. Genetic sequencing found two biofilm-related genes consistently present in stone-associated bacteria, suggesting potential targets for new treatments. Host immune proteins also contribute to stone formation, with stones containing layers of crystals and organic material. Preliminary data show certain proteins are more active when both E. coli and CaOx are present, forming layered stones. The hypothesis is that interactions between CaOx crystals, immune proteins, and bacteria facilitate stone formation. Aim 1 involves measuring how stone matrix proteins and bacteria interact to promote stone formation, while Aim 2 focuses on studying biofilm-related genes in stone-associated bacteria, using genomics and transcriptomics to identify and validate these genes. This research could lead to innovative treatments targeting specific bacterial genes and mechanisms to prevent and treat kidney stones.

NIAID - National Institute of Allergy and Infectious Diseases

Abstract Since the medical breakthroughs of surfactant and synchronized mechanical ventilation in the 1990’s, there have been few new interventions that have substantially impacted morbidity and mortality of infants born at extremely low gestational ages (ELGANs), resulting in stalled even increased common morbidities. The most common ELGAN morbidities, including central white matter disease, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy and sepsis share features of inflammation, suggesting immune-mediated damage may be a common causal pathway. However, there are major gaps in our understanding of normal human fetal and postnatal immune development in full-term infants, and even more so in preterm infants, which are born at a development stage of the immune system which was not meant to encounter the non-sterile extra-uterine environment. These gaps have limited our ability to discern, let alone treat harmful activated immune pathways. To make matters even more complicated in ELGANs, some age-associated immune pathways are necessary for sustained organ development, as evidenced by our previous work showing that ELGANs whose T cells do not follow an expected pattern of change over time are at higher risk for respiratory illnesses later in infancy. Thus, there is a critical need to understand both the molecular program that defines normal immune maturation, as well as the earliest timing during which abnormally developing immune pathways are likely to respond to intervention postnatally. The overall goal of the project is to identify key age-associated immune pathways in ELGANs T cells that can be targeted for treatments. We hypothesize that there is an underlying immune program that meets the unique demands of a developing fetus, but this program is vulnerable to disruption by common postnatal exposures, including antibiotics, during the first postnatal month. To address this hypothesis, we aim to 1) model typical and atypical longitudinal age-determined T cell subset trajectories in ELGANs, 2) frame a postnatal window during which immune trajectories are susceptible to modulation using discovery proteomics, 3) determine the gene regulatory program in ELGANs using single cell genomics, 4) Identify immune changes associated with a common exposure, antibiotics, and potential gene targets to mitigate their harmful effects. Successful completion of this study will provide the highest resolution immune trajectories during the most dynamic period of postnatal immune system development. These results will enable us to direct novel immunomodulatory therapies at the appropriate postnatal age in order to promote normal immune system development in ELGANs.

HEALTH AND HUMAN SERVICES, DEPARTMENT OF.NATIONAL INSTITUTES OF HEALTH.ADVANCED RESEARCH PROJECTS AGENCY FOR HEALTH (ARPA-H)

Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) Innovative Solutions Opening (ISO)

DECD

Critical Municipal Infrastructure

NCIPC - National Center for Injury Prevention and Control

Project Abstract/Summary: The Earned Income Tax Credit (EITC) plays a critical part in the social safety net by increasing financial security for low to moderate income working families, particularly the 5.4 million households headed by single female parents with low education. The EITC has been identified as a promising primary prevention strategy for preventing child injury and risk factors for youth violence. However, program design fails vulnerable first-time mothers. EITC payments are so limited for first-time mothers that researchers have used less educated, single first-time mothers as the “control” group to establish the positive impacts of the EITC. Our central hypothesis is that current EITC design contributes to higher child abuse and neglect and youth violence and exacerbates health inequities for groups already experiencing disproportionate burdens of violence. The EITC gap exists as women pregnant with their first child receive little to no EITC benefit until 2-14 months following birth despite strong evidence that stress, nutrition, and economic well-being during pregnancy and early infancy impact a lifetime of outcomes including experiences with violence. Our long-term goal is to support the health and well- being of families by equitably reducing experiences with violence. The overall objective of this application is to estimate how EITC policy design impacts outcomes for first children and how this contributes to the disproportionate burden of violence. We update the existing literature on EITC effects with a combination of data sources and causal design and provide the first estimates of the child abuse and neglect and youth violence improvements possible by closing the EITC gap for first-time mothers. Specific Aim 1: To quantify child abuse and neglect and youth violence effects that would be achieved by closing the EITC gap for first births. Specific Aim 2: To understand community member perspectives on risk factors for child abuse and neglect and youth violence including EITC eligibility. Specific Aim 3: To estimate a simulation model of the costs and benefits of closing the EITC coverage gaps for first-time mothers. 3.1: Assess the CAN and youth violence effects of closing the EITC gap at the federal level. 3.2: Separately estimate impacts of the EITC gap for people disproportionately impacted by violence based on disability status and race and ethnicity and assess the role of the EITC gap in perpetuating disproportionate burdens of violence.

DECD

Critical Town Infrastructure Repairs

Crocker Art Museum Foundation

Crocker Art Museum Foundation is an active grantmaking foundation based in Sacramento, CA. Focus: arts. Contact the foundation directly for current funding opportunities.

Queen Anne Greenways

This project involves working with the community to create a permanent public plaza on a half block of W. Crockett Street between Queen Anne Ave. N. and 1st Ave. W., the site of a successful temporary public plaza under a caf� street permit in 2020 and 2021. The project seeks community engagement in identifying design solutions through broadly marketed gatherings (both in person and virtual) over the summer and fall of 2022. Following public input, a designer will produce drawings and three-dimensional renderings that reflect the program and suggested project elements. Since we all benefit from public space, we intend, as part of this effort, to work with SDOT to create a clear and equitable process for others to create public plazas in their neighborhoods. This project will be completed by February 28,2023.

Crohn's and Colitis Canada

Funds research to find cures for Crohn's disease and ulcerative colitis. Supports new investigator awards and operating grants.

Town Of Cromwell

Priority

Town of Cromwell

Priority

City of Madras

Crook-Jefferson Emergency Rent Assistance Program

City of Madras

Crook-Jefferson Emergency Rent Assistance Program

DOT

Cross Highway Sidewalk Improvements

The Common Acre

The Common Acre will host a public event featuring Indigenous cultural traditions and environmental educational activities to promote pollinator habitat restoration on public land. It will take place on September 15, 2018 from 10am - 3 pm at 10617 53rd Ave S.

Citizens for a Safer First Hill

The intersection at 9th Ave. & Columbia St. is accessed by various community groups, including seniors, business associates, children, dog walkers and more. Despite clearly painted marks on the road and bright safety signs, visibility is difficult due mainly to the parked cars on either side of the intersection. Attaching cross walk flags at each end of the cross walk is a low cost, but high impact change that will make it safer and more accessible to cross the street.