Grants

Middlebury

Bioski Road Top

NIAID - National Institute of Allergy and Infectious Diseases

Natural products (aka specialized metabolites) are small molecules produced by bacteria, fungi, plants, and animals that have found many uses in agricultural, veterinary, and human health. More than half of all currently FDA approved drugs are natural products or derived from natural products. In addition, to their far- ranging biological activities (anti-cancer to anti-bacterial to anti-viral) the pathways that organisms utilize to construct natural products from simple, readily available building blocks, particularly those used by microbes, have triggered much interest. Both as a way to understand the mechanisms and enzymes to allow manipulation of the proteins and pathways to produce new-to-nature natural products with altered biological activity and from an intellectual standpoint. In this proposal, we dissect the mechanism of ureido bond formation in the biosynthesis of three families of bioactive bacterial natural products, the anabaenopeptins, the syringolins, and the muramycins, which derive from diverse bacterial genera. These biologically active molecules contain the proteolytically stable ureido bond, which is a key contributor to their biological activity. While the mechanism of ureido formation in biotin biosynthesis has been studied, we hypothesize that the biosynthesis of the anabaenopeptins, syringolins, and muramycins, which are all assembled through the action of a non-ribosomal peptide synthetase (NRPS), are distinct due to the fact that the intermediates are tethered to the NRPS in contrast to the untethered biotin intermediate, 7,8-diaminononanoate. Our preliminary data suggests that the mechanism utilized in the biosynthesis of the anabaenopeptins is distinct from the mechanism previously proposed for the biosynthesis of the syringolins. This proposal describes a multidisciplinary approach consisting of protein overexpression, isotope labeling, and chemical trapping in Aim 1, which is complemented by cryo-EM, and site directed mutagenesis in Aim 2. These specific aims will allow the elucidation of the mechanism utilized during ureido bond formation while identifying the protein residues and motifs involved in substrate binding and catalysis in proteins found in different bacterial genera and with different protein architectures. The identification of the motifs will allow the proper annotation of ureido bond forming condensation domains found in deposited sequenced genomes, which is an issue as they are currently annotated as having amide bond forming activity by popular annotation software like AntiSMASH. This prevents the accurate prediction of compound structure from genomic data and represents a current hurdle in the field of natural products. The knowledge gained in this proposal will set the stage for the future engineering of new natural products with altered biological activity by introducing ureido bonds to increase proteolytic stability and alter physiochemical properties.

NIGMS - National Institute of General Medical Sciences

Project Summary. Nucleoside analogs are an important class of pharmaceutical compounds that serve as the cornerstone for antiviral therapy. Beyond viral infections, various nucleoside analogs have also shown antitumor, antibacterial, antifungal, and herbicidal activity. Though synthetic chemists can design new nucleoside analogs de novo, a large fraction of our pharmaceuticals are inspired by bioactive compounds made by bacteria. The proposed work will investigate the biosynthesis of a cryptic family of natural product nucleoside analogs that contain ‘rare’ functional groups. This work will be enabled by the research group’s expertise on non-standard nucleoside biochemistry, chemical biology, genetics, and analytical chemistry. Initial work will combine genetic engineering with comparative genomic/comparative metabolomics to identify key enzymes involved in halogenation and sulfamate formation. Since these perform valuable transformations, they make promising candidates as biocatalysts for pharmaceutical synthesis. Notably, kinetic and substrate/reaction characterization of these enzymes will be explored test the feasibly of using these enzymes for alternative synthesis of existing nucleoside analog therapeutics. As a subsequent goal, this work will also explore how ‘modular’ biosynthesis of these nucleoside natural products can be used to rapidly synthesize inhibitors of a wide-range of enzymes. Key innovations here will include combinatorial assays with ribozyme components. Finally, this work will look to integrate bioinformatic/metabolomic/genetic approaches to discover unknown nucleoside analogs made by various bacteria. Specifically, we highlight existing evidence of hybrid gene clusters that make unknown nucleosides. As a general vision, this research program poses that elucidating nucleoside biosynthesis pathways, characterizing enzymes that perform rare biochemistry, and discovering new bioactive nucleosides will expand the repertoire of biocatalytic tools available for making life-saving nucleoside analogs.

NSF

A St. Louis bioscience labor market analysis showed within the St. Louis, Missouri region, biosciences account for over 19,000 jobs at over 800 firms, roughly two-thirds of which are in research, testing and medical labs, and biomanufacturing. Bioscience employers in the region project 1400 job openings annually between 2021 and 2031, the majority of which require a high school diploma and short-term training or an associate's degree. As only one biotechnology program currently exists at a community college in the region, there is a clear need for additional programs that can supply the much-needed employees for the biosciences industry. St. Charles Community College proposes to establish a biotechnology program to educate skilled biotechnicians to meet the critical need for highly skilled, entry-level and mid-level biotechnician and biomanufacturing positions in the region. The project objectives are to (1) develop and implement a new Associate of Applied Science (A.A.S.) degree in biotechnology with industry-aligned, stackable certificates; (2) prepare students to earn industry-recognized certifications and microcredentials, such as the Biotechnician Assistant Credentialing Exam (BACE) or Bioscience Core Skills Institute (BCSI); (3) establish strong workforce connections in order to create a work-based experiential program that supports retention, degree and certificate completion, industry-recognized certifications, and workforce readiness; and (4) create and implement a robust K-12 high school recruitment program. This project is funded by the Advanced Technological Education program that focuses on the education of technicians for the advanced-technology fields that drive the nation's economy. 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.

City of Richmond

Bioxytech Retina, Inc

Tolland Town Treasurer

Priority

Tolland Town Treasurer

Non-Priority

Tolland Town Treasurer

Non-Priority

Lower East Side Girls Club of New York

To support the establishment of a research lab focused on pollinator habitat around the organization's recently installed rooftop meadow.

Lower East Side Girls Club of New York

To support the establishment of a research lab focused on pollinator habitat around the organization's recently installed rooftop meadow.

Birmingham Education Foundation

Birmingham Education Foundation is an active grantmaking foundation based in Birmingham, AL. Focus: education. Contact the foundation directly for current funding opportunities.

Gallagher Asphalt Corporation

Land and Buildings and Structures and Thoroughfares

Builder's Asphalt LLC

Bituminous material distributors

GALLAGHER MATERIALS CORP

Land and Buildings and Structures and Thoroughfares

SP APPROP Municipal Restructuring

BJH Advisors DRI

NHLBI - National Heart Lung and Blood Institute

Mitochondria have been shown to play a central role in cardiac contractility and the process is tightly regulated by electron transport chain (ETC) efficiency. Mitochondrial functions including ATP generation and ROS production by ETC are tightly coupled with ionic homeostasis and coordinated regulated signaling between nuclear-cytoplasmic and mitochondrial components. Tremendous progress has been made in deciphering the mechanistic role of mitochondria in protecting the heart from cardiac hypertrophy in animal models. Yet, it remains a substantial challenge to dissect the critical contribution of mitochondria to cardiac hypertrophy and to establish a rigorous relationship between energetics, signaling pathways, and specific aspects of cellular and organ hypertrophy. The potassium channel sensitive to voltage and calcium (BK) present in cardiomyocytes has been shown as a splice variant of plasma membrane BK and is exclusively present in mitochondrial membranes (referred to as mitoBK). Though activation of cardiac mitoBK is known to play a role in cardioprotection possibly by regulation of mitochondrial function, the precise mechanism of mitoBK in regulating cardiac function and protecting the heart from pathological hypertrophy (or cardioprotection from IR injury) is not yet established. We will now test the hypotheses that: cardiac mitoBK protects against pathological cardiac hypertrophy by regulating mitochondrial biogenesis and function via modulating the levels of UCPs, through signaling pathways governed by PGC-1α, and FOXO3a. Our published, as well as preliminary data, show that: 1) mitoBKCa is encoded by Kcnma1 gene, and a DEC splice variant governs its mitochondrial localization; 2) absence of mitoBK causes cardiac hypertrophy, fibrosis, and cardiac dysfunction; 3) absence of mitoBK augment cardiac hypertrophy after pressure overload insult whereas genetic activation protects the heart, 4) expression of mitoBK is vital for handing mitochondrial calcium and ROS levels after pressure overload, 5) absence of mitoBK results in changes in expression of UCPs, PGC-1α, and FOXO3a. Our preliminary data support our hypothesis that cardiac mitoBK, exclusively present in the mitochondria of adult cardiomyocytes, plays a cardioprotective role in cardiac hypertrophy. This will be tested by an array of multidisciplinary collaborative approaches using mouse genetics. In that regard, we will pursue the following specific aims: 1) To determine the role and mechanisms of mitoBK channel mediated changes in mitochondrial function in left ventricular hypertrophy; and 2) To elucidate mechanisms whereby retrograde signaling influences mitoBK activity, and expression of transcriptional coactivators and UCPs in left ventricular hypertrophy. This research program will be the first proposal that will determine the precise signaling mechanism of how cardiac mitoBK channels directly play a role in mitochondrial physiology, and cardiac function, and protect the heart from pathological cardiac hypertrophy.

Black and Tan Project

On October 1st and 2nd of 2022, the Black and Tan Community Group will commemorate the 100 year anniversary of the opening of The Black and Tan Nightclub, at Langston Hughes Performing Arts Center. At the time, the first and only interracial nightclub in The Pacific Northwest. This historical event will consist of Two live performances will be held at the LHPAI followed by a reception. Our group is focused on bringing Arts, Culture and Theatre to the community free of charge! The event is free and open to the public.

Aktionsart

Black Box is the first festival in Seattle to showcase local and international artists who expand the language of cinema through technology. To attract and introduce a large audience to new art forms, several containers scattered around town will be presenting new media works. With its multiple platforms and free admission, Black Box has been designed for its public and partners to enjoy an integral experience of art.

Sundiata African American Cultural Association

A two day festival at Langston Hughes Performing Arts Center, 104 17th Avenue South, will be held during February of 2017 in celebration of Black History month. There will be food, vendors, art, music, as well as informative presentations on the contributions of African Americans in the United States. This is a free family friendly event with something for all ages.

LOCAL ASST (S)

Black Institute Working Capital

City of Gainesville

Black on Black Crime Task Force

Seattle Chapter of the Black Panther Party Anniversary Committee

The Seattle Chapter of the Black Panther Party will celebrate their 50th anniversary through a series of outreach activities that share the challenges and successes of the Party. They will take place during the fall and winter of 2017. The culminating event will be a three-day conference to be held at Seattle University in April of 2018 featuring panels, workshops, and discussions on issues related to human rights, activism, and social justice. All events are free and open to the public.

Estelita's Library

Estelita's Library currently holds one of the worlds largest collections of Black Panther Newspapers, with more than 300 papers spanning the duration of the existence of the newspaper. Currently, our collection is in paper form which makes it difficult for us to share it broadly with the community. Through this project, we will engage community members in a series of 6 free workshops from July 2024-May 2025 teaching them the fundamentals of digital archiving. The community will build out an archive featuring their own resistance stories, as well as archiving our collection of Black Panther Newspapers. The archive will be available, free-of-cost, by community request either by emailing or dropping in to our public open hours. This work will culminate in a free Community Archive Launch Party in April 2025.

BRRALLIANCE INC

This project will focus on educating, training, and equipping residents in designated DAC areas on how to monitor the quality of the air in their homes, how they can improve that quality, and why it is important to do so to improve their health.