Grants

Christian Church Foundation For The Handicapped

Christian Church Foundation For The Handicapped is an active grantmaking foundation based in Louisville, TN. Focus: social services. Contact the foundation directly for current funding opportunities.

Christian Hospital Foundation

Christian Hospital Foundation is an active grantmaking foundation based in St Louis, MO. Focus: health. Contact the foundation directly for current funding opportunities.

Christian Youth Foundation

Christian Youth Foundation is an active grantmaking foundation based in Athens, TX. Focus: community development. Contact the foundation directly for current funding opportunities.

Coro-Dante

Christmas Choral Concert

Lake County

Christmas Valley Library Building

Lake County

Christmas Valley Library Building

New York Foundation for the Arts

Christopher Grant - Scrambled Eggs - multi-media theatrical project

The Wooster Group, Inc.

Christopher Kondek - For Billy

Christus Childrens Foundation

Christus Childrens Foundation is an active grantmaking foundation based in San Antonio, TX. Focus: health. Contact the foundation directly for current funding opportunities.

Christus Foundation For Healthcare

Christus Foundation For Healthcare is an active grantmaking foundation based in Houston, TX. Focus: health. Contact the foundation directly for current funding opportunities.

Ledyard

Christy Hill Subdivision Paving

NSF

The marine phytoplankton Synechococcus senses and responds to changes in the ratio of blue to green light in its environment. This response, called the Type 4 Chromatic Acclimation (CA4), allows these cells to efficiently adjust their photosynthetic machinery to optimally capture the most abundant of these two light colors. This is important because the amount of blue and green light varies tremendously throughout the ocean and light availability usually limits photosynthesis and growth. Synechococcus is the second most abundant photosynthetic organism in the oceans, where about 50% of the photosynthesis on Earth occurs. Therefore, studying CA4 will provide important insights into the regulation of photosynthesis on our planet. In addition, CA4 appears to be sensing light color through completely novel photoreceptors. This project characterizes these CA4 elements and the mechanisms through which they work, providing basic understanding for the application of important new components in Biotechnology, specifically in Synthetic Biology and Optogenetics. An understanding of the mechanisms of the CA4 elements could lead to improved process control by blue and green light during industrial processes. This project contains activities to encourage high school students to enter STEM disciplines and integrates education and research through the participation of high school teachers and students. This project's goal is to define the regulatory mechanisms controlling changes in the photosynthetic light harvesting antennae of the phytoplankton Synechococcus spp., the second most abundant photosynthetic marine organism. This process, called Type 4 Chromatic Acclimation (CA4), allows cells to sense the ratio of blue to green light and alter the transcriptional activity of specific genes. Two approaches will be used to define this regulatory system. First, light-sensing chromophores associated with the two putative, novel photoreceptors FciA and FciB will be identified by purifying epitope-tagged versions from CRISPR transformed Synechococcus cells and analyzing them using spectroscopy and mass spectrometry. Second, the CA4-responsive DNA binding sites of CA4-regulated genes will be identified by joining their upstream regions to reporter genes and replacing specific DNA sequences of these regions, then introducing these genes into Synechococcus to identify CA4 control elements. DNA binding by FciA and FciB, which are also putative transcription factors, will be examined in blue and green light using ChIP-seq and DNA footprinting. These AraC family proteins are likely the first of a new photoreceptor class. The CA4 blue-green light regulatory system will be potentially valuable for use in Systems Biology and Optogenetics. 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.

NSF

The remarkable complexity of the mammalian brain arises from precisely regulated genetic programs that control neural cell number and diversity during embryonic development. Epigenetic mechanisms—heritable modifications that influence gene expression without changing the DNA sequence—are central to orchestrating these programs. However, how epigenetic regulation in neural stem cells determines neuronal number and diversity in the developing brain remains poorly understood. This proposal addresses this critical gap by leveraging sophisticated mouse genetic models and cutting-edge DNA sequencing technologies to investigate the role of epigenetic modifications in cerebral cortex development. The resulting insights will deepen our fundamental understanding of mammalian, including human, cortical development. Furthermore, this work will illuminate how disruptions in epigenetic regulation contribute to the cellular and molecular defects underlying some neurodevelopmental disorders, such as autism. Complementing the research, the proposal includes a comprehensive educational initiative to engage and train high school students, teachers, and both undergraduate and graduate students in the fields of genomics, epigenetics, and neurodevelopment. Central to understanding developmental cell commitment is elucidating how epigenetic mechanisms silence alternative cell fates. These mechanisms, mediated by chemical modifications in chromatin, play a crucial role in regulating gene expression programs. A defining feature of transcriptionally silent chromatin (heterochromatin) is the di- and tri-methylation of histone H3 at lysine 9 (H3K9me2 and H3K9me3). Previous studies indicate that H3K9-methylated heterochromatin acts as a barrier to cell fate conversions, underscoring its critical role in promoting cell commitment and preserving cell identity. However, how distinct H3K9 methylation states regulate neurogenesis and cell fate specification in the developing mammalian brain remains unknown. Here, we generated mouse genetic models to deplete H3K9me2 or H3K9me3 in the embryonic cerebral cortex. Our preliminary data show that H3K9me2 and H3K9me3 occupy distinct chromatin regions and control different aspects of cortical neurogenesis. In this proposal, we will dissect the molecular mechanisms of gene silencing by H3K9me2/3 in the cortical lineage. These insights will advance our understanding of neurodevelopmental disorders in which H3K9-methylated heterochromatin may play a central role. This project is jointly funded by the Genetic Mechanisms Program of the Division of Molecular and Cellular Biosciences (MCB) and by the Neural Systems Program of the Division of Integrative Organismal Systems (IOS) in the Directorate for Biological Sciences (BIO). 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.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY Ischemic heart disease following myocardial infarction (MI) is a leading cause of global morbidity and mortality. During MI, infiltrating immune cells, particularly monocytes, differentiate into macrophages, adopting both reparative and maladaptive pro-inflammatory roles. These maladaptive immune responses can drive chronic inflammation, adverse remodeling, and ultimately heart failure (HF) progression. Although blocking monocyte recruitment has been explored as a therapeutic strategy, this approach risks impairing the essential reparative functions required for proper wound healing and scar formation post-MI. Thus, understanding chromatin and gene regulatory mechanisms controlling monocyte differentiation and macrophage activation is critical for developing therapies that selectively target maladaptive pro-inflammatory responses while preserving reparative functions. BRD4, a member of the BET protein family, is a key epigenetic regulator of chromatin dynamics and transcription during inflammation. Our preliminary data show that BRD4 plays a pivotal role in shaping pro-inflammatory macrophage phenotypes during MI. While pharmacological BET inhibition using JQ1 can reduce inflammation and improve cardiac function, systemic toxicity limits its therapeutic potential. To address this, we use a novel Brd4 conditional allele combined with the Ccr2creERT2 mouse model to achieve monocyte-specific BRD4 deletion. The goal of this project is to elucidate BRD4-mediated chromatin and gene regulatory networks (GRNs) that control monocyte differentiation and macrophage function during MI and to identify therapeutic strategies that selectively modulate maladaptive inflammation. Aim 1 will define how Brd4 deletion in CCR2+ monocytes affects macrophage fate and cardiac function post-MI, using flow cytometry and scRNA-seq to track macrophage differentiation and assess physiological impacts. Aim 2 will investigate BRD4’s role in regulating macrophage activation, combining CUT&RUN and CRISPR interference to map BRD4 binding and its influence on MHC-II gene expression and other pro-inflammatory programs. Aim 3 will use proteomics to identify BRD4 protein interactors in macrophages, focusing on PU.1, to understand how it modulates BRD4 function during pro- inflammatory activation. This work will generate a comprehensive map of BRD4-regulated transcriptional and chromatin dynamics in immune cells, providing new therapeutic targets that limit maladaptive macrophage activation, reduce chronic inflammation, and improve outcomes in HF patients.

NIGMS - National Institute of General Medical Sciences

Project Summary Among all endosymbionts, maternally transmitted Wolbachia bacteria are the most common, due in large part to their ability to influence host reproduction to spread. Many Wolbachia cause cytoplasmic incompatibility (CI), a sperm modification that kills embryos without Wolbachia. Two prophage-associated genes (cifA and cifB) cause and one gene (cifA) rescues CI. Cytologically, CI produces cycle-1 defects in embryogenesis when paternal chromosomes fail to properly condense. However, CI-derived embryos regularly escape cycle-1 defects and display chromosome segregation defects later in embryogenesis during the cortical divisions (10- 14). Further, some individuals fully escape CI, proceeding to larval and even adult life stages. This has resulted in a large gap in knowledge about whether a common acute CI mechanism acts at different time points, or if independent and temporally distinct mechanisms underlie these patterns. The proposed research will fill this gap in knowledge by integrating genetic, cytogenetic, and genomic analyses to determine the primary cellular defect underlying embryonic lethality in the context of two mechanistic models. The host-modification (HM) model predicts that Cifs modify male gametes prior to fertilization, while the toxin-antidote (TA) model predicts that Wolbachia produce a Cif toxin that is transferred directly to the embryo. The presence of independent defects beyond cycle-1 lends support to the HM model since a putative toxin is unlikely to persist throughout embryogenesis. Elegant experiments have tracked cycle-1 mitotic defects to errors at the histone-protamine transition in spermatogenesis that cause abnormal levels of paternal histones in sperm nuclei. Very recent data also indicate a reduction of H3K9me2,3—a marker of inactive heterochromatin—in CI crosses. These data support the hypothesis that CI-causing Wolbachia modify host chromatin and interfere with the histone post- translational-modifications (PTM) required for normal histone removal. The proposed work will determine if histone PTMs are maintained through development in embryos and larvae which ‘escape’ embryonic death. Chromosome structure will then be evaluated in larvae to determine the relationship between histone PTMs and decondensed chromosomes. To determine the genome-wide effects of CI-induced chromatin changes, chromatin accessibility in embryos will be mapped using single-cell ATAC-seq. This technique was chosen to specifically identify differentially condensed genomic regions in the presence of Wolbachia. Finally, a Position Effect Variegation screen will be used to assay effects on gene expression as a functional output of the chromatin states. In addition to preparing the applicant for a long-term career as a principal investigator, this work will fill critical gaps in knowledge by tracking the chromatin state changes that occur with CI and determining if a single mechanism underlies CI death. This work will contribute to our broader knowledge of CI, which is critical for explaining global Wolbachia prevalence in natural populations and to improving the efficacy of Wolbachia biocontrol of human disease transmission in transinfected vector populations.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ABSTRACT Introduction. In the United States, the decline in HIV incidence over the preceding decades had stalled. In New York City, over 129,000 people are currently living with HIV/AIDS, around 1.4% of the population. Paramount to bringing about the end of the HIV epidemic, is ensuring that these individuals are engaged with medical care leading to antiretroviral therapy that suppresses the replication of HIV. This outcome not only improves the lives of people living with HIV but also precludes the possibility of onward sexual transmission. Success along the HIV care continuum—from diagnosis, to linkage to care, to antiretroviral therapy, to viral suppression—is facilitated by name-based HIV surveillance by public health departments. Ensuring success along the care continuum, including re-engagement with care, falls to local public health surveillance and prevention personnel. This public health surveillance approach, known as data-to-care, also includes the analysis of HIV genetic sequences produced for drug-resistance screening (i.e., molecular epidemiology), which can be used to characterize clusters of HIV transmission. Across the United States, these transmission clusters are used to prioritize public health services to reduce HIV incidence and facilitate engagement in care. These clusters can be useful in understanding trends in diagnosis rates as well as progression through the care continuum. However, nearly half of people with a recent HIV diagnosis lack a reported HIV genetic sequence. Methods. Here, we propose a retrospective study designed to evaluate the impact of these public health activities currently implemented in NYC. First, we will determine whether people without a reported HIV sequence—who are overlooked in molecular HIV surveillance activities—have faster or slower progression through the care continuum including re-engagement with care, compared with people who have a reported HIV sequence. Second, we will determine whether shared membership in molecular transmission clusters can be used to predict the success of re- engagement with care services resulting viral suppression. Third, we will develop a novel phylodynamic framework that permits the analysis of longitudinally-sampled data (e.g., HIV viral load and CD4+ count) in a viral phylogenetic trees to determine the relationship between viral suppression/re-engagement with care services and incident transmission in HIV transmission clusters. Conclusions. This study will provide a comprehensive picture of how HIV molecular epidemiology informed public health action can lead to success along the HIV care continuum improve and how this success can accelerate the decline of the HIV epidemic in the United States.

NIAID - National Institute of Allergy and Infectious Diseases

Modified Project Summary/Abstract Section Aedes aegypti transmits several arboviral diseases, including dengue and Zika fever, which threaten virtually half of the world’s human population. Two subspecies, Ae. aegypti aegypti (Aaa) and Ae. aegypti formosus (Aaf), have been described based on their body coloration. These subspecies differ remarkably from each other in their worldwide distribution, association with humans, and ability to transmit pathogens. In Anopheles populations, polymorphic inversions are often responsible for epidemiologically important phenotypes but our knowledge about chromosomal rearrangements in Aedes populations is limited. Although our recent study identifies a large pool of structural variation in the Ae. aegypti genome, their impact on behavior and adaptations of this species remains completely unknown. We hypothesize that chromosomal inversions contribute to the remarkable phenotypic and genetic plasticity of Ae. aegypti. However, more studies are needed to better understand the geographical patterns of the inversion distribution all over the globe and their potential involvement in ecotypic differentiations of the Ae. aegypti subspecies. Our project will test whether chromosomal rearrangements are 1) subspecies specific; 2) associated with ecological variables in Africa; 3) involved in mosquito adaptations to human. In this study, we will take advantage of the improved, fully re-annotated genome assembly for Ae. aegypti, employ the Hi-C approach and SNP-based inversion genotyping in publicly available WGS sequencing data to characterize chromosomal rearrangements across the world-wide distribution. We will also apply simple and robust PCR-based approaches to identify presence of common African inversions in individual mosquitoes in Senegal and use RNA-seq to determine differences in transcriptional profiles of standard and inverted genotypes. Our long-term goal is to understand the underlying genomic determinants of epidemiologically important phenotypic and behavioral differentiation of Ae. aegypti mosquitoes. Toward this end, we propose three specific aims: 1) identify patterns of world-wide distribution of the chromosomal rearrangements in Ae. aegypti and their associations with Ae. aegypti subspecies; 2) test if widely spread chromosomal inversions are associated with ecological variables in Africa; 3) determine specific transcriptional profiles associated with standard and inverted homokaryotypes of common African inversion 1pA. The discovery of chromosomal inversions in Ae. aegypti will stimulate future genetic studies aimed at preventing mosquito-borne disease transmission

NIGMS - National Institute of General Medical Sciences

Project Summary (30 lines) Meiosis is a tightly controlled process during which the diploid genome must segregate into haploid gametes (e.g. eggs or sperm). Inheritance of the incorrect number of chromosomes is a leading cause of fertility and birth defects. However, the reasons for chromosome missegregation are not always the same for all chromosomes. Why inter-chromosomal differences exist is still unclear. One key contributor appears to be either a complete loss of crossing over or abnormal crossover placement. Drosophila melanogaster is a powerful model to better elucidate the regulation of chromosome-specific crossing over and the effects on chromosome segregation. In most cases, mutants that disrupt crossing over do so uniformly across the genome making it difficult to understand how chromosome-specific defects occur. However, a set of mutants in a partial loss-of-function synaptonemal complex mutant exhibit substantially different defects in pairing and recombination on the X chromosome and the autosomes. The synaptonemal complex is a conserved meiotic structure that holds homologous chromosomes together and is necessary for crossing over. The long-term goal of this project is to understand the chromosome-specific mechanisms that lead to error-free meiotic outcomes. This work will investigate 1) how chromosomes are identified as unique by the meiotic machinery and 2) how positioning of DSBs and crossovers is regulated on specific chromosomes. Overall, this project will provide insights into both the regulation of crossover location and meiotic chromosome biology. By studying the importance of individual chromosome behaviors and the synaptonemal complex in recombination, substantial advances can be made in understand the biology underlying the development of aneuploidies.

African American Reach and Teach Health

The African American Reach and Teach, (AARTH), is planning educational activities and forums that focus on chronic diseases and mental health outreach. The forums will take place at 5237 Rainer Avenue South. AARTH will develop and host a series of information awareness activities on chronic diseases including diabetes, chronic kidney disease, and mental illness. Peer leader trainings will also be held. The main goal is to increase awareness and knowledge on how to better address chronic health conditions, reduce the stigma of mental illness and create a network of peer supporters for a healthier, more conscious society. The outreach will take place between January and December 2020.

Chuckanut Health Foundation

Chuckanut Health Foundation is an active grantmaking foundation based in Bellingham, WA. Focus: general. Contact the foundation directly for current funding opportunities.

City of Richmond

Angel Beauty Supply

DOT

Church Street Renovation

DOT

Church Street road, drainage, sewer and sidewalk project

Claverack

Churchtown Fire District Consolidation Study