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City of Seattle Department of Neighborhoods

Matching grants for arts, culture, and community building projects in Seattle neighborhoods. Requires community match.

Seattle Repertory Theatre

On December 10, 2021, Seattle Rep's Public Works department will produce a virtual event featuring Lear DeBessonet and Todd Almond?s musical adaptation of THE WINTER'S TALE in collaboration with a group of up to eight community partners. Rooted in the values of equity, imagination, and joy, this project will advance arts equity and provide arts access to communities that have historically been excluded from the arts by using theater as a tool for equity and inclusion. The virtual event will be free and expect to reach at least 2,000 households on both a local and national scale. Project completion date will be February 28, 2022.

Seattle Sister Cities Association

The Sister Cities Signpost is intended to increase awareness of Seattle's Sister City Program and its position as a global city by having a piece of public art that would showcase the names of each of Seattle's Sister Cities. The design includes sign blades made in colors that will blend in with the Seattle sunset while also providing an attractive piece of public art that will be a colorful contrast against our often-grey skies. The anticipated project completion date is December 31, 2025.

Seattle-Isfahan Sister City Advocacy (SISCA)

Free and open to the public, the fifth annual Seattle-Isfahan Sister City Advocacy (SISCA) Persian New Year (Nowruz) celebration from 12 pm to 5 pm, Sunday, March 23, 2025, will transform Seattle City Hall into a vibrant, colorful, energy-filled space. We aim to celebrate the art, culture, and traditions from the spectrum of local immigrant co-celebrant Persian-heritage cultures including Iran, Afghanistan, Uzbekistan, and Turkey. The Lobby will feature displays of traditional and modern Persian artwork and craft demonstrations, as well as local Persian-focused NGOs at information tables, and a Kids Corner. The auditorium will host lively performances of dance, music, and song; speakers from across the diaspora; and elected officials. We expect 1,500 attendees with half of non-Persian-heritage. Our goal is to benefit and lift up our communities by celebrating together and to help counter the persistent negative images of so many Persianate countries that appear in U.S. media.

Seattle Artist Coalition for Equitable Development

On The Block Second Saturdays is a series of monthly outdoor street markets on 11th Ave between E. Union and E. Pine every Second Saturday of the month from July through September of 2025. Created for and by local BIPOC artists, this free, all-ages event features a marketplace of over 38 local vendors selling handmade goods, vintage, street fashion, and more along with 3x3 basketball tournaments, interactive art, community activations, and over 6 hours of DJ and live performances. As an alliance among neighboring artists, cultural spaces, and small business owners, the mission of On The Block Second Saturdays is to be a conduit to sustainable opportunity, creative equity, and abundance from the ground up, amplifying local creativity and generating a safer, more connected neighborhood. This project will be completed by October 31, 2025.

NIMH - National Institute of Mental Health

While several studies have characterized myeloid cells as the primary central nervous system (CNS) HIV reservoirs on long-term suppressive antiretroviral therapy (ART), significant knowledge gaps remain in understanding the role of CD4+ T cells in CNS reservoir seeding, viral persistence, and neuropathogenesis. The characterization, and ultimate eradication, of HIV persistence and neuroinflammation remain key goals of HIV research and defining the roles of T cells and their interactions with CNS cell populations driving these processes are essential. In this application, we propose to leverage our validated nonhuman primate model of HIV neuropathogenesis and persistence, our experience defining early CNS seeding, and past studies of T cell sequestration, to determine the impact of blocking T cell circulation during acute SHIV infection on the establishment of durable brain reservoirs. Our model of CNS persistence uses TF SHIV.D.191859 (SHIV.D), a CCR5-tropic virus that efficiently replicates in both CD4+ T cells and macrophages, and consistently infects the CNS, causes neuroinflammation, and persists through ART via long-lived myeloid reservoirs. Genetically barcoded SHIV.D has been validated in persistence experiments, enabling tracking of clonotypes across tissues over time. Our recent studies of barcoded SHIV.D-infected, ART-treated NHP have shown early seeding of the brain that persists through durable ART. Our team has also demonstrated in ART-suppressed SIV-infected rhesus macaques (RMs) that a clinically approved immunomodulating therapy for multiple sclerosis, FTY720, results in rapid and near-complete redistribution of CD4+ T cells from blood into peripheral tissues, with minimal impact on blood monocytes. Thus, FTY720-induced inhibition of T cell, but not monocyte, migration will enable us to dissect the specific role of CD4+ T cells in trafficking of SHIV to the brain and establishing short- and long- term brain reservoirs. RMs will be infected with barcoded SHIV.D and then treated with FTY720 either 1 week prior to infection (Arm 1), or 7 days post-infection (Arm 2), or left untreated (Arm 3). ART will be administered 1- month post-infection, with half of the animals in each arm to undergo necropsy early at 1 month ART, or later at 6 months ART. Arm 4 animals will be infected and receive FTY720 only and be necropsied at study month 2 to compare the effects of FTY720 without ART. In these coordinated NHP studies, we will test our hypothesis that FTY720-mediated inhibition of T cell migration to the brain will prevent early seeding of SHIV brain reservoirs, will limit the size and diversity of the persistent CNS reservoir, and will reduce neuroinflammation on suppressive ART. Using an array of molecular, immunohistochemical, and single cell analyses, we will assess the impact of peripheral CD4+ T cell sequestration on early and late SHIV brain reservoir seeding, then characterize the impacts on neuroinflammation and neurodegeneration. These studies will provide valuable insight into the role of CD4+ T cells in CNS reservoir seeding, including their contribution compared to monocytes, the timing of the reservoir establishment, and their contribution to neuroinflammation.

NIA - National Institute on Aging

PROJECT SUMMARY. Alzheimer's disease (AD) is characterized not only by progressive memory loss but also by a range of non- cognitive deficits, including sleep disturbances and autonomic dysfunction. Emerging evidence implicates herpes simplex virus type 1 (HSV-1) as a critical environmental trigger that accelerates AD pathology. Our preliminary data demonstrates that HSV-1 preferentially infects the locus coeruleus (LC) and paraventricular nucleus of the hypothalamus (PVN) in both wild-type (WT) and AD mouse model mice—key regulators of non- cognitive functions—to induce early amyloid deposition, tau hyperphosphorylation, and neuroinflammatory responses, ultimately exacerbating AD progression. Furthermore, HSV-1 exacerbates microglia dysfunction and amyloid accumulation in AD mice. These observations raise a critical question: does HSV-1 infection initiate early transcriptional and post-translational changes in the LC and PVN that accelerate physiological and behavioral deficits? In this proposal, we hypothesize that HSV-1 induces Aβ and NFT formation in the LC and PVN, triggering a hyperinflammatory response prior to hippocampal involvement. To test this hypothesis, we will employ an integrated, multidisciplinary approach using advanced spatial transcriptomics and proteomics (via the NanoString GeoMx DSP platform) alongside in vivo electrophysiological (EEG/LFP) and behavioral assays (using FED3 feeding devices). Aim 1 will delineate the spatial and temporal molecular alterations in the LC and PVN following intranasal HSV-1 infection in 3xTg AD mouse models and WT controls. This analysis will focus on the regional accumulation of amyloid and tau pathologies, microglial activation, and associated gene expression changes that precede hippocampal involvement. In Aim 2, we will link these molecular changes to functional outcomes by monitoring disruptions in LC activity, sleep-wake cycles, EEG rhythms, and feeding behavior. This study is innovative in its use of state-of-the-art spatial omics combined with rigorous neurophysiological and behavioral assessments to bridge the gap between molecular pathology and functional deficits in AD. The outcomes are expected to provide critical insights into HSV-1's role in triggering early AD pathogenesis, particularly in non-cognitive domains, and may identify novel targets for early intervention. Ultimately, this research will help reshape our understanding of viral contributions to neurodegenerative processes and inform the development of therapeutic strategies aimed at mitigating both cognitive and non-cognitive symptoms of AD.

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT Cryptococcal meningitis (CM), a devastating disease of the central nervous system (CNS) caused by the encapsulated fungus Cryptococcus neoformans (Cn), occurs mainly in people with HIV (PWH) with profound CD4T (CD4) cell loss. In a 2020 analysis, globally, there were 152,000 CM cases accounting for 19% of AIDS- related mortality. While cryptococcal antigen (CrAg) screening, antiretroviral therapy (ART), and potent antifungal drugs have led to earlier diagnosis and improved outcomes, mortality remains inexplicably high. The landmark >800 participant phase III randomized controlled AMBIsome Therapy Induction OptimizatiON-cryptococcal meningitis trial (AMBITION, heretofore ‘Ambition’) in African PWH with CM comparing a single dose of Liposomal Amphotericin B (L-Amb) to WHO-recommended first-line induction with Amphotericin B deoxycholate found L- AmB was noninferior, but mortality was high, 25% L-AmB, 29%, WHO, and highest (37%) in recent ART initiators. Although there were fewer adverse events with L-AmB, leading WHO to recommend a practice change to the L- AmB regimen, there are no correlates of survival or treatment response for PWH with CM. This is a major roadblock to improving CM outcomes as clinicians lack tools to make management decisions for those who do not improve, such as when and in whom to use corticosteroids or intensify antifungals. The hypothesis of this application is that certain plasma immunoglobulin (Ig) measures are associated with survival and treatment response in PWH with CM. The project builds on our extensive data showing that 1) Cn elicits distinct antibody responses in PWH with asymptomatic latency (CrAg-/CM-) and antigenemia (CrAg+) and those with disease (CM); 2) Cn capsular polysaccharide glucuronoxylomannan (GXM)-IgG levels were associated with survival in PWH with antigenemia and trended so in CM; 3) human Cn-binding Igs promote Fc receptor (FcR)-mediated antifungal activity; and 4) normal human Igs bind and alter Cn virulence features. Leveraging these data and our deep knowledge of human Cn immunity and antibody responses, we propose three aims to identify serological correlates of survival and treatment response in existing de-identified plasma samples from the full 844 participant Ambition cohort provided by principal investigator, Joe Jarvis. Aim 1: To identify associations between survival and plasma isotype/subclass and Cn binding-Ig levels in Ambition participants. Aim 2: To compare survival, Ig FcγR functional activity and FcγR polymorphisms of Ambition participants on ART ≤2wks prior to randomization matched 1:1 to those not on ART. Aim 3: To use systems serology and computational platforms to identify signatures of survival and treatment response in Ambition participants, integrating Ig features with survival status, clinical, microbiologic, and laboratory data. Clinicians urgently need correlates of CM survival and treatment response to guide management to improve outcomes and reduce mortality. Data generated in this project will be poised for validation in ongoing and prospective cohorts of PWH with CM and other high-risk groups to inform treatment guidance and development of adjunctive antibody therapies to improve CM outcomes.

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT Human immunodeficiency virus-1 (HIV-1) remains incurable except in rare cases. The ultimate barrier to sustained remission without continuous antiretroviral therapy (ART) is the HIV-1 reservoir, which remains under-characterized, particularly across individuals who differ by age, sex, and ART history. This submission is for a Mentored Patient-Oriented Research Career Development Award (K23) entitled “Sex Differences in HIV-1 Reservoir- a Multi-omic Approach to Identify Mechanisms of Reservoir Decay”. I am an Assistant Professor at the University of Pittsburgh specializing in HIV medicine and general infectious diseases. I developed this proposal to leverage multi-dimensional platforms to investigate drivers of change in the HIV-1 reservoir over a decade of suppressive ART, with the ultimate goal of identifying new approaches to eliminating the HIV-1 reservoir. It seeks to examine the longitudinal decay patterns of intact proviruses, a robust marker for the HIV-1 reservoir. I am particularly interested in the interaction between age, sex, hormone levels, HIV-1 immune responses, and HIV-1 reservoir dynamics. My preliminary study, supported by the Rustbelt Center for AIDS Research (CFAR) pilot funding, suggests there are distinct patterns of HIV-1 provirus decay and immunological correlates in females compared to males with HIV. Further studies and training are needed to take these preliminary findings to the next level and systematically dissect the chronological, virological, immunological, and hormonal influences of HIV-1 reservoir dynamics. The findings from this proposed study would help identify therapeutic targets for HIV-1 reservoir clearance. To gain the skills necessary to achieve my career goal of becoming an independent translational physician-scientist, I propose this career development plan that includes mentoring from Drs. John Mellors, Charles Rinaldo, and Mark Cameron (primary mentors), along with Drs. Bernard Macatangay, Sharon Riddler, and Nicolas Sluis-Cremer (advisory team). This team represents research leaders across HIV-1 virology, immunology, single-cell sequencing, and systems biology. This project will utilize de-identified data and samples obtained from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study Combined Cohort (MWCCS), a four-decade longitudinal multicenter cohort studying individuals with or at high risk for HIV- 1 infection. Dr. Charles Rinaldo, one of the primary mentors for this project, is also one of the founding scientists of MWCCS. The proposed work will be conducted at the Division of Infectious Diseases at the University of Pittsburgh, Pittsburgh, PA and Case Western Reserve University Comprehensive Cancer Center, Cleveland, OH. Guided by highly supportive mentors who are the top experts in their fields, with unwavering support from my department, I am confident that I will acquire the skillset required to perform cutting-edge translational studies on the HIV-1 reservoir that will lead to innovative approaches to achieve HIV-1 remission. 1

NHLBI - National Heart Lung and Blood Institute

ABSTRACT This proposal requests NHLBI support for the 2026 Scientific Sessions meeting presented by the Council on Basic Cardiovascular Sciences (BCVS) of the American Heart Association (AHA). This meeting has become the “go to” meeting for basic and translational cardiovascular sciences by providing opportunities for established and emerging investigators to present their work and receive constructive feedback. The meeting in 2026 represents the 21st consecutive annual conference. Funding for BCVS Scientific Sessions from National Heart, Lung and Blood Institute (NHLBI) has been secured for 17 of the last 19 years. The BCVS summer conference is entitled “Shaping the Future of Cardiovascular Medicine: Integrating Basic Science Breakthroughs to Clinical Impact”. In 2025, our in-person conference was a rousing success with about 1,000 investigators from around the world. We plan to again hold an in-person meeting in 2026 to help facilitate the careers and networking opportunities for young investigators and support collaborations. The meeting is scheduled for July 13-July 16, 2026 and will begin on a Monday and run through Thursday. The conference will highlight the newest basic and translational cardiovascular research with implications for cardiovascular health and disease. There will be approximately 14 scheduled state-of-the-art sessions that include a mix of established and emerging investigators. The 2026 BCVS keynote address will be given by Dr. Johnathan Epstein, a Robert G. Dunlop Professor, who serves as Dean of Perelman School of Medicine and Executive Vice President of the University of Pennsylvania for the Health System. There are specific sessions for early career scientists, including two early career sessions, an Early Career Keynote Lecture, and the Outstanding Early Career Investigator Award Competition. We will host special sessions for networking including interactions with journal editors and staff. We will also include a Networking Breakfast to support scientists. This R13 proposal is designed to provide support to young investigators to enable their participation in the meeting as presenters either in oral or poster format. The primary organizers are Drs. Farah Sheikh and Jennifer Davis. The Program Committee (11 members) includes the past program co-chair and leadership from across the US drawn from the many disciplines encompassed by BCVS. The AHA will continue to provide its outstanding administrative support with dedicated staff for the logistics of the conference. We fully anticipate that this team will coordinate an exceptional 2026 BCVS conference.

National Institutes of Health

This Notice of Funding Opportunity (NOFO) announces the restructured Shared Instrumentation Grant (SIG) Program that consolidates three existing shared-use instrumentation programs, i.e., the Shared Instrumentation Grant program, the High-End Instrumentation Grant program, and the Basic Instrumentation Grant program. The NOFO invites applications from groups of NIH-supported investigators to purchase or upgrade a single state-of-the-art commercially available instrument or an integrated instrumentation system. The instruments purchased through the SIG Program are required to be optimally shared among the users to ensure efficient and cost-effective research operations, enable rigorous and reproducible measurements, and encourage collaborative research and benefit broad research communities at large. The minimum award is $300,000. There is no cap on the total cost of the instrument; however, the maximum award is $5,000,000. Cost sharing is required for premium instruments or special use instruments.

National Institutes of Health

This Notice of Funding Opportunity (NOFO) announces the restructured Shared Instrumentation Grant (SIG) Program that consolidates three existing shared-use instrumentation programs, i.e., the Shared Instrumentation Grant program, the High-End Instrumentation Grant program, and the Basic Instrumentation Grant program. The NOFO invites applications from groups of NIH-supported investigators to purchase or upgrade a single state-of-the-art commercially available instrument or an integrated instrumentation system. The instruments purchased through the SIG Program are required to be optimally shared among the users to ensure efficient and cost-effective research operations, enable rigorous and reproducible measurements, and encourage collaborative research and benefit broad research communities at large. The minimum award is $300,000. There is no cap on the total cost of the instrument; however, the maximum award is $5,000,000. Cost sharing is required for premium instruments or special use instruments.

Jackson Place Business Association

The independent businesses, storefronts, art studios, live/ work BIPOC, LGBTQ+ creative spaces make our neighborhood a more vibrant and desirable place to live and work. Together with our residents, people who work in the area and new visitors who discover our unique neighborhood we hope to grow a stronger sense of community through the installation of holiday lighting on our small dead-end street called the Hiawatha Arts & Business Corridor located on the 800 block of Hiawatha Place South. This project will contribute to better public safety by creating a more attractive and interesting area for visitors to discover, explore, and feel safe walking their pets at night, returning to the neighborhood through public transportation, or patronizing the storefronts or community space in the center of the block. This project will be completed by April 29, 2022.

National Institutes of Health

NIDA seeks to further advance its mission in the area of single cell biology. Since 2020, the NIDA-funded Single Cell Opioid Responses in the Context of HIV (SCORCH) consortium has generated single-nucleus datasets from human and animal postmortem brain tissue under conditions of HIV infection, antiretroviral therapy (ART), and/or substance exposure (e.g. opioids, cocaine, methamphetamine, and cannabinoids). Building on this Phase 1 foundation, NIDA will encourage research addressing critical questions on Substance Use Disorder (SUD) and interactions with HIV disease progression at the subcellular, cellular, or circuit levels in the Central Nervous System (CNS). Many new cutting-edge single cell approaches (e.g. interrogation of RNA splicing, non-coding RNAs, epigenomic or proteomic features, subcellular or synaptic localization and function, spatial interactions, cell-cell communication, or cellular connectivity) now enable novel hypothesis-generating studies. Along with data mining studies to identify candidate mechanisms or targets contributing to HIV/SUD interactions and hypothesis-driven studies to assess functional significance, we expect SCORCH Phase 2 to significantly advance our mechanistic understanding of SUDs and HIV in the CNS and identify targets for novel therapies. Grant authorities that allow NIDA to forecast this opportunity are 42 U.S.C. 241 and 284

National Institutes of Health

<p>NIDA seeks to further advance its mission in the area of single cell biology.&nbsp; Since 2020, the NIDA-funded Single Cell Opioid Responses in the Context of HIV (SCORCH) consortium has generated single-nucleus datasets from human and animal postmortem brain tissue under conditions of HIV infection, antiretroviral therapy (ART), and/or substance exposure (e.g. opioids, cocaine, methamphetamine, and cannabinoids).&nbsp; Building on this Phase 1 foundation, NIDA will encourage research addressing critical questions on Substance Use Disorder (SUD) and interactions with HIV disease progression at the subcellular, cellular, or circuit levels in the Central Nervous System (CNS).&nbsp; Many new cutting-edge single cell approaches (e.g. interrogation of RNA splicing, non-coding RNAs, epigenomic or proteomic features, subcellular or synaptic localization and function, spatial interactions, cell-cell communication, or cellular connectivity) now enable novel hypothesis-generating studies.&nbsp; Along with data mining&nbsp;studies to identify candidate mechanisms or targets contributing to HIV/SUD interactions and hypothesis-driven studies to assess functional significance, we expect SCORCH Phase 2 to significantly advance our mechanistic understanding of SUDs and HIV in the CNS and identify targets for novel therapies.&nbsp; Grant authorities that allow NIDA to&nbsp;forecast this opportunity are 42 U.S.C. §§ 241 and 284</p>

Sioux Falls Area Community Foundation

Sioux Falls Area Community Foundation ($400M in assets) supports nonprofits in SD through grants focused on education, community development, health, arts. Awards range from $2,000 to $100,000.

NIA - National Institute on Aging

Project Summary Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of hyaline cartilage lining articular joints. A critical challenge for OA management is the development of an effective treatment that reverses cartilage damage. Our previous work indicates the existence of adult skeletal stem cells (SSCs) in postnatal cartilage. These SSCs are dormant yet can potentially repair damaged cartilage when stimulated by surgical procedures such as Microfracture (MF). While MF typically results in the formation of inferior fibrocartilage, we have demonstrated that MF-activated tissue-resident SSCs can be expanded and directed towards the formation of healthy chondrocytes and hyaline cartilage to regenerate full-thickness cartilage defects by pharmacologically modulating SSC activity and the microenvironment surrounding them. This method we termed Growth-factor Enhanced Microfracture (GEM). Our published studies and preliminary data demonstrate that GEM works well in young animals but is less effective in aged mice. Our data supported by recent findings of others further suggest that FGF7 (Fibroblast Growth Factor 7) expression in the SSC lineage is induced by an inflammatory aged and osteoarthritic bone marrow niche, which leads to pro-fibrotic lineage-skewing resulting in cartilage loss. We now build on additional preliminary results showing that direct and indirect blockade of FGF7 during GEM can reinstate stem cell-based cartilage formation in joints of aged and OA mice. The gained insights from the proposed study will help us to develop strategies to efficiently apply GEM even in impaired settings with a cellular microenvironment less conducive to articular cartilage regeneration. To that end, we are elucidating the cellular dynamics and molecular mechanisms that underlie SSC mediated cartilage repair. In Aim 1, we will expand our preliminary findings to confirm and mechanistically dissect how inhibiting FGF7 locally during GEM in aged and osteoarthritic mice can promote hyaline cartilage formation. In Aim 2, we will determine if epigenetic rewiring of local SSCs by a novel therapeutic compound is sufficient to overcome age-related impairments of GEM mediated cartilage regeneration. Our experiments will use state-of-the-art structural and functional readouts at the tissue level as well as latest technology to unravel cellular and molecular changes at the single cell level to assess regenerative properties and provide new biological insights into OA. Our team brings together expertise in skeletal stem cell biology, in-depth basic science and clinical knowledge of OA as well as bioengineering competency. We are using cutting-edge methods to pursue hypothesis-driven questions aimed at unlocking endogenous stem cells for cartilage repair. By taking advantage of a therapeutic window to skew local MF-activated SSC fate we want to generate new cartilage for the resurfacing of OA joints independent of age and disease state. Eventually, we wish to translate these preclinical studies.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY: SKIN-TARGETED METAL-ORGANIC FRAMEWORK-BASED SUBUNIT VACCINES Driven by their affordability, manufacturability, and safety benefits over traditional vaccines, subunit antigens are an important component of modern vaccinology. However, they exhibit poor immunogenicity and efficacy, and thus, new and rational strategies are required to improve their immunogenicity and efficacy. We propose a novel skin immunization platform (SIP) to address the limitations of vaccine development with subunit antigens. Our innovative and globally deployable SIP leverages emerging vaccine technologies, including (1) metal-organic framework (MOF) nanovaccine constructs; (2) a clinically de-risked adjuvant, and (3) needle-free, thermostable, and self-applied microneedle arrays (MNAs), as well as highly immunoresponsive skin niche for the development of effective and accessible subunit vaccines. The central hypothesis of our project is that in situ harnessing of the immunologically rich milieu of skin with our SIP in a spatially and temporally controlled manner will drive the generation of robust, durable antigen-specific humoral and cellular responses in a well-tolerated manner. Our SIP is engineered in the form of rapidly separable MNAs (rsMNAs) that consist of high-quality obelisk-shaped microneedles comprising dissolving polymer matrix tips loaded with MOF vaccine constructs and non-dissolvable stems with filleted bases attached to the backing layer. Unlike traditional MNAs that require relatively longer wear times (minutes), our rsMNA design, which is enabled by the unique ability of biodegradable MOFs in protecting vaccine components against denaturing organic solvents needed to form non-dissolvable stems of microneedles, facilitates the implantation of MOF vaccines into the skin in less than 10 s via shear force. Our SIP offers the superior vaccine delivery and immunogenicity characteristics compared to needle-and-syringe (N&S) vaccines and conventional MNA-based vaccines. As such, our SIP unlocks the true potential of the skin immune system for improved cutaneous vaccination strategies with subunit antigens. Ultimately, this project will yield a rapidly translatable SIP that will provide unparalleled flexibility and efficacy for vaccination with subunit antigens, which is unattainable with the state-of-the-art immunization platforms.

Thingyverse

Thingyverse will create the nation's first touring arts performance program designed for babies and toddlers. This free and open to public performance program will consist of two workshops and 4 performances at different locations throughout Seattle starting January 2020. And the first workshop will be held at the Magnuson Community Center - 7110 62nd Ave NE.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY: The currently available antiretrovirals can effectively control HIV-1 replication and thus prevent disease pro- gression to AIDS. Such antiretroviral treatment (ART), however, cannot eradicate the infection. Latently infect- ed cells persist through ART and, if ART is stopped, will lead to rebound of viral replications within weeks. In- fected individuals therefore need to take medications for the entire life span and consequently suffer from drug resistance as well as severe side effects including cardiovascular complications, metabolic disorders, and neu- rocognitive damage. Novel antiretrovirals that could eliminate HIV-1 infection and cure the disease is thus high- ly desired. It is believed that HIV cure could be possibly achieved through empowering host immune cells to recognize and kill HIV-1-infected cells. One significant barrier here, however, is that HIV-1 has evolved mech- anisms that enable infected cells to evade host immunity. A key player here is the HIV-1 Nef protein. Nef is a master regulator of HIV-1 immune evasion. By downregulating MHC-I from the surface of the host cell, Nef dis- rupts host cell’s antigen presentation, which then allows the infected cell to evade immune surveillance by host cytotoxic T lymphocytes (CTLs). Nef also downregulates CD4 from the cell surface; this benefits the infected cell in several ways including evading killing by natural killer (NK) cells through antibody-dependent cellular cytotoxicity (ADCC). Inhibition of these Nef functions should revitalize both CTLs and NK cells, empowering them to find and kill HIV-1 infected cells. This project is aimed at developing such inhibitors and thus overcome the barrier of viral immune evasion to facilitate the cure. Four in vitro assays have been developed and opti- mized for screening small molecule libraries to find inhibitors. Two assays, orthogonal to each other, are both capable of identifying inhibitors that can block Nef’s activity on MHC-I and CTLs (having two orthogonal assays here allows cross-validation of hits to ensure discovery of true inhibitors). Another two assays, also orthogonal to each other, are capable of finding inhibitors that can block Nef’s activity on CD4 and ADCC. These assays have been tested in a proof-of-concept screen against a medium-sized compound library. All four assays per- formed excellently, indicating their suitability for high-throughput screening. A hit compound has been found from this modest screen and was subsequently validated through concentration-dependent studies in vitro. Building on these promising results, we now propose to carry out—using our developed assays and the estab- lished workflow—large-scale library screens to identify inhibitors against the two targeted Nef functions (Aim 1). We will then use both in vitro and cell-based assays to characterize inhibitors and identify those with out- standing potency and efficacy (Aim 2). We will also solve high-resolution structures of inhibitor-Nef complexes and then use the structural information obtained to guide chemical derivatization of lead compounds (Aim 3). Upon completion of the project, we will obtain potent inhibitors of Nef-mediated immune evasion, ready for fur- ther development into real-world antiretrovirals to facilitate HIV cure.

Columbia City Theater Group

Local artists, activists, and educators will collaborate to offer Seattle youth the opportunity to build community through production of a theatrical play, film festival, graphic-novel adaptation, and accompanying resources. These creative projects will build community and engage youth in social justice through the rich tradition of storytelling and the exploration of race, socioeconomics, education, and the arts.

SODEC

SODEC supports Quebec's cultural enterprises including film, television, music, publishing, and performing arts through grants and financing programs.

OD - NIH Office of the Director

ABSTRACT/SUMMARY This proposal requests funds to purchase a Liberty Blue 2.0 solid-phase peptide synthesizer. At present, Vanderbilt lacks a comparable capacity for customized peptide synthesis, compelling researchers to rely on commercial vendors. While standard peptides can often be sourced at reasonable cost, the synthesis of peptides incorporating non-proteinogenic amino acids, macrocyclizations, or site-specific chemical modifications incurs prohibitive costs and prolonged lead times. These limitations negatively affect numerous NIH-funded research programs and severely lowers the chemical novelty accessible to investigators who make use of peptides in their research. Acquisition of an institutional instrument will directly address this gap, enabling timely and affordable access to high-quality, customized peptides that are increasingly central to modern biomedical research. This instrument will serve a large and scientifically expansive group of investigators across 15 departments in the College of Arts and Science, the School of Medicine Basic Sciences, and the Vanderbilt Institute of Chemical Biology. Investigators from the Vanderbilt University Medical Center will also have access. The user base spans a wide array of NIH-funded projects that rely on synthetic peptides. For example, one group synthesizes fluorophore-labeled peptides to monitor receptor trafficking. Another develops cleavable linkers that release antibiotics from antibody-drug conjugates designed to target methicillin-resistant Staphylococcus aureus. A third focuses on macrocyclic peptides that modulate the activity of CFTR and thus show promise as future therapeutics for cystic fibrosis. Several other groups engage heavily in structure- and AI-guided design and require rapid synthesis of candidate molecules to support downstream biochemical and cellular validation. The Liberty Blue 2.0, manufactured by CEM Corporation, uses microwave-assisted chemistry to accelerate synthesis cycles, improve coupling efficiency, and enhance overall yield and purity. The instrument accommodates a wide range of chemistries and scales, offering flexibility to support exploratory screening, structure-activity relationship campaigns, and early-stage preclinical development. Importantly, it also provides significant cost and time savings compared to commercial synthesis, especially for chemically complex sequences. The instrument will be housed within the Molecular Design and Synthesis Core, which has provided synthetic chemistry expertise and training to the Vanderbilt community since 2006. This core will oversee daily operation and user access, supported by administrative and financial contributions from the School of Medicine Basic Sciences and the College of Arts and Science. Acquisition of the Liberty Blue 2.0 will significantly enhance Vanderbilt’s infrastructure for chemical biology, lower the barrier to peptide-based experimentation, and accelerate discovery across multiple scientific disciplines and therapeutic categories.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY The project supports ongoing efforts in the Shea group geared at developing new computational methodologies and tools to study the liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs). Biomolecular condensates formed by LLPS play a range of vital physiological roles in the body, but under aberrant conditions, they can transition into amyloid fibrils, a process linked to disease. The project will meld artificial intelligence protein-language models with a multiscale computational framework to accurately simulate the dilute and dense LLPS phases, characterize the role of water, co-solvents, and high pressure in modulating assembly, and identify new LLPS-prone sequences in the human proteome. The proposal consists of three research projects. Project 1 involves the development of a tightly integrated multiscale computational approach bridging the atomistic to mesoscopic time and length scales. The relative entropy approach will be used to generate chemically accurate protein and water coarse-grained models from atomistic simulations, which will be used as input for efficient field theoretic simulations. The latter will be used to generate phase diagrams for the LLPS of the microtubule-binding Tau protein and Elastin-Like Polypeptides (ELPs), with field theoretic outputs backmapped to generate atomistic, solvated condensate structures that can be directly compared to experiment. Project two involves the development of new high pressure Kirkwood-Buff force fields for the osmolyte trimethylamine N-oxide (TMAO) from experimental Kirkwood-Buff Integrals, and their application to the study of TMAO’s counteraction of high-pressure denaturation of ELP condensates. Project 3 involves developing new artificial intelligence protein language model tools to mine the IDRome – the 28k proteome of intrinsically disordered regions – for new LLPS-prone and co-condensating sequences. The research will lead to state-of- the-art computational tools that will be deposited in Github and made freely available to the broad scientific community, to new physical insights into osmolyte and pressure modulation of LLPS, and to the discovery of new LLPS-prone sequences. The research will inform on conditions that promote functional forms of LLPS as well as lay the foundation for rational therapies for condensate-linked diseases.