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European Commission - HORIZON

“Artistic intelligence” : harnessing the power of the arts to address complex challenges, enhance soft skills and boost innovation and competitiveness. Call: Culture, Creativity and Inclusive Society 2026. Programme: HORIZON. Keywords: Arts, Art history, Creativity management, Design innovation, Experimentally-driven research and innovation, ICT & art, Life long learning, Mental health, Open innovation, Social innovation, Social sciences, interdisciplinary, Visual arts, performing arts, design. Open call from the EU Funding & Tenders Portal.

Belltown Art Walk

The Belltown Artwalk community group will be hosting an art exhibit located at the Slip Galley 2301 1st Ave on Jan 10, 2025. The exhibit will feature four artist as they delve into themes of self perception, identity, and the complexities of internal dialogue. Through curated pieces that explore the fluid and often distorted boundaries between mind, body, and self, viewers are invited into deeply personal reflections. The show will also hosts two free public workshops aimed at fostering introspection and self-expression. The event is free and open to the public.

OD - NIH Office of the Director

Twenty-four NIH-funded investigators studying a wide range of biomedical research topics at the University of Maryland Baltimore (UMB) are requesting funds for a transmission electron microscope (TEM), the Talos L120C G2 (Thermo Fisher Scientific). UMB has a long history of TEM use conducted at the Electron Microscopy Core Imaging Facility (EMCIF), and the decommissioning of the current TEM has drastically impeded the ongoing research projects. This TEM will replace an 20-year-old Thermo Tecnai T12, a 120 kV tungsten filament instrument, whose reliability and stability were decreasing when we lost the capability to capture images. Through demonstrations of microscopes from several vendors as well as Director and user experiences, the Thermo Talos L120C G2 is the ideal replacement research microscope with its high-contrast, high-resolution optics for biological samples. Its lanthanum hexaboride crystal electron source and Ceta 16M CMOS and Smart digital camera will produce bright, well-contrasted images for all our users. Its user-friendly software interface with features such as motorized stage, alignment recall, automated apertures, and rapid specimen exchange make this a good fit for a core facility. The remote operation features are ideal for training users and providing fee-for-service to distant users. The Talos L120C will be placed in the current TEM room, which is a pre-existing, well-designed space with convenient access to the main Core lab and staff. It will be administered by the EMCIF which is part of the Center for Innovative Biomedical Resources (CIBR) which provides resources to UMB researchers. Our staff will provide training in sample preparation and in operation of the new TEM. EMCIF is jointly supported by the School of Dentistry and the School of Medicine. We support research across the entire UMB campus as well as the University of Maryland System. The new TEM will be placed into the existing recharge system available to users through an iLab software interface available through the web and as a smart phone app. The new TEM will support continued progress of NIH-funded research projects of UMB scientists that are relevant to our mission of improving the human condition and serve the public good of Maryland. The EMCIF has a strong record of collaboration with researchers providing electron microscopy results for presentations, publications and grant applications. Strong institutional support provides for Director and staff salaries, space, instrument service/maintenance, administrative services and other EMCIF operating costs. If funded, the Talos L120C will be the primary TEM for UMB faculty research, and it will expand our capacity for biomedical research at UMB and at regional institutions. The impact will extend beyond the cancer, blood, infectious disease, bone development and other research projects listed in this proposal. The EMCIF’s mission is to provide state-of-the-art instrumentation and training to researchers, trainees, graduate students and staff. We aim to train the next generation of scientists to appreciate and interpret electron micrographs.

National Park Service

This year's festival will celebrate the 100th Anniversary of Anacostia Park and the Year of the Anacostia a year-long invitation to HONOR history, CELEBRATE progress and ENJOY the Anacostia River and its surroundings as we ENVISION an inspiring future. Festival activities will include: boating, fishing workshops, hands-on art projects, musical performances, bike parades, and other unique programs engaging families with the river, its history and ecology. This FREE event aims to encourage District residents and tourists alike to explore communities and parks east of the Anacostia River.

NIEHS - National Institute of Environmental Health Sciences

The Gordon Research Conference on Environmental Sciences: Water is to be held June 14-19, 2026, in Holderness, NH. The 2026 conference theme is Novel Approaches and Tools to Address Aquatic Impacts on Human and Environmental Health and will feature a program of thought-provoking research by leading researchers and experts in the field of water quality science and technology. The conference will bring together 190 participants from multiple countries in an immersive and informal setting. The program will feature a series of plenary talks by established and emerging researchers, as well as daily poster sessions by conference attendees. The overarching theme of the 2026 conference recognizes that state-of-the-art research is needed to understand challenges facing water resources, and to develop solutions to address these challenges. Ensuring water quality is critical for protecting human and ecosystem health, as well as maintaining ecosystem services. This conference will showcase innovative researchers who focus on current water resources challenges, including the presence of persistent contaminants and pathogens, access to clean water for communities, and environmental stresses on water. This aspect of the conference will provide a forum for discussing and evaluating the most pressing water issues of our time. The conference will highlight scientists who directly study environmental impacts through field measurements and community engagement, along with those working at the science-policy interface. Specific aims of the conference are to: 1) Feature a scientific program that links water quality issues, the protection of human health, and sustainability of environmental resources through a plenary program of leading researchers from different fields and perspectives - themes include chemical and biological exposures, human health impacts, and innovative solutions for the management of water resources; 2) Advance discovery while promoting mentoring, networking and learning by offering a platform for graduate student and postdoctoral researchers to present their research at the full conference, as well as provide a venue for informal interactions between senior scientists and trainees and broad participation of scientists from different professional settings; and 3) Provide a conference that fosters discussion and debate of research results through close interaction of participants from academia, industry, and government laboratories. Funds will be used to support the attendance of invited plenary speakers, as well as graduate students and postdoctoral trainees. Outcomes related to the quality of the scientific program, discussion, management, and atmosphere will be evaluated through surveys of conference attendees. 1

NHLBI - National Heart Lung and Blood Institute

ABSTRACT Abnormal lipid and lipoprotein metabolism is mechanistically linked to many common diseases such as obesity, fatty liver, diabetes, cardiovascular disease (CVD), and neurodegenerative diseases. The Gordon Research Conference (GRC) on Lipoprotein Metabolism is recognized as a premier meeting for disseminating cutting-edge research, sparking collaborations, and fostering new paradigms in this fast-moving field. The 2026 GRC will continue this tradition of highlighting research excellence in various areas of lipid and lipoprotein metabolism. The conference, to be held in Waterville Valley, NH from June 2-7, will focus on important new developments in lipid and lipoprotein metabolism relevant to human disease. Oral presentations (in 9 integrated sessions) will highlight state-of-the-art scientific approaches, exploring molecular, structural and cell biological studies, model systems of metabolism, and preclinical and human studies of new therapeutic targets. The overarching goal is to bring together scientists from diverse research areas, career stages, and geographical locations who share a passion for discovering and applying new paradigms in lipid and lipoprotein metabolism to improve human health. The GRC will be preceded by the Gordon Research Seminar (GRS), a forum for trainees to present their research in a setting of mentorship and inspiration provided by peers and selected faculty in attendance. The First Aim of the 2026 GRC on Lipoprotein Metabolism is the communication of cutting-edge, unpublished science on lipoprotein metabolism. This includes 45 presentations in 9 oral sessions, each with an identified theme and a discussion leader who will facilitate dialogue and encourage participation by all attendees. Several of the oral sessions will feature short presentations by trainees and early career investigators, selected from submitted abstracts by a panel of established investigators. The roster of confirmed speakers is an impressive array of leading researchers from a range of career stages and represent the world’s best scientists in the area of lipid and lipoprotein metabolism. Our Second Aim is to achieve broad participation and engagement opportunities for all attendees. GRCs place high priority on the principles of safety and the creation of a welcoming environment. The 2026 GRC on Lipoprotein Metabolism has long-standing reputation as a safe and engaging meeting for all participants to share their unpublished results in a collegial manner. We expect this meeting to discuss the opportunities and challenges for emerging therapies for diseases such as CVD, obesity, diabetes, fatty liver disease, and Alzheimer’s and related dementias. Collectively, we expect the 2026 Gordon Research Conference (GRC) on Lipoprotein Metabolism to improve human health through promoting open dialogue, collaboration, and scientific innovation.

NIA - National Institute on Aging

Project Summary NIH supported research aims to advance our understanding of biological systems, improve the control of disease, and enhance health. It is well-recognized that connecting investigators with complementary expertise’s in fundamental cell biology, biochemistry, genetics, state of the art imaging with those developing avenues for the treatment of disease are essential to get effective advances. This grant proposal seeks support for the 2026 Gordon Research Conference (GRC) and associated Gordon Research Seminar (GRS) on Lysosomes and Endocytosis, with a central theme of “Endosomes and Lysosomes in Action Across Cells, Tissues and Disease States”. As the field of Lysosomes and endocytosis evolves with increasing research in this aging related topics, the 2026 meeting will place an important emphasis on neurodegenerative disease, specifically Alzheimer Disease and related aging disorders. Exploring at the cellular, molecular and structural levels how defects in lysosomal and endocytic processes contribute to disease onset and progression are essential fundaments for therapeutical intervention. Endosomes and lysosomes are critical components of the endomembrane system, orchestrating essential cellular processes including cargo sorting, degradation, membrane trafficking, and signaling. Their coordinated activity ensures proper cellular homeostasis and adaptability across a wide range of cell types and tissue environments. Emerging evidence highlights their dynamic and context-dependent roles in development, immunity, metabolism, and cell fate determination. Notably, dysregulation of endo-lysosomal pathways is increasingly recognized as a central contributor to the pathogenesis of numerous diseases, including neurodegenerative disorders, cancers, metabolic syndromes, and lysosomal storage diseases. The GRC will bring together internationally recognized experts and emerging scientists to present unpublished data, stimulate discussion, and develop new collaborations. The GRS, held prior to the main conference, will offer a focused environment for trainees and junior researchers to present their work and build professional networks to boost their careers.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY The 2026 Gordon Research Conference on Membrane Transport Proteins, “The Dynamic Membrane Transporter: Gateways to Health & Disease,” will convene ~200 investigators from academia, industry, and medicine at the Renaissance Tuscany Il Ciocco, June 14–19 (trainee-led GRS, June 13–14). This location facilitates participation by a broad international community of scientist, trainees, and early-career scientists working on membrane transport proteins. The broader scientific exchange directly benefits public health in the United States by speeding advances in the understanding of disease mechanisms, the development of new drugs, and the identification of promising therapeutic strategies. It also ensures that the United States researchers remain fully engaged with the discoveries, technologies, and research shaping drug discovery in this important field. Membrane transporters comprise roughly 10 % of the human genome, yet fewer than 4 % are clinically exploited, despite their central roles in prevalent disorders, including autism, depression, ADHD, addiction, and diabetes, and in rare diseases such as Christianson syndrome and mucoviscidosis. Breakthroughs in cryo-EM, AI-driven structure prediction, live-cell biosensors, and human-derived disease models now make it possible to translate fundamental transporter biology into first-in-class therapeutics, creating a timely need for a forum that seamlessly links molecular mechanisms to clinical applications. The program’s nine themed sessions and two plenary lectures deliberately pair structural and mechanistic discoveries with preclinical and clinical perspectives, covering topics from vesicular neurotransmitter loading and blood–brain-barrier gateways to ABC/OCT1-mediated drug disposition. Interwoven “Technology Spotlight” talks and “Reality-Check” panels will showcase state-of-the-art methods while candidly addressing their limitations, establishing rigorous, field-wide standards. A 1.5-day, trainee-run Gordon Research Seminar, anchored by keynote mentors Drs. Sara Jones and Walter Boron, plus mentoring innovations such as “Scientist Speed-Dating” lunches and the forum Breaking the Mold: Overcoming Barriers to Career Advancement will foster an inclusive, supportive environment that cultivates the next generation of transporter scientists. Guided by three specific aims, catalyzing translational science, elevating rigor and reproducibility, and building a global workforce, the conference is poised to reveal new transporter ligands, biomarkers, and drug-delivery strategies; to disseminate best-practice methodologies; and to launch enduring mentorship networks. By uniting siloed disciplines in a confidential, off-the-record environment that encourages presentation of unpublished data, the 2026 GRC will accelerate transporter-based solutions for some of today’s most urgent unmet medical needs.

NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development

Project Summary The Neural Development Gordon Research Conference (GRC) is a premier, international scientific conference focused on advancing the frontiers of science through the presentation of cutting-edge and unpublished re- search, prioritizing time for discussion after each talk and fostering informal interactions among scientists of all career stages. The conference program includes a broad range of speakers and discussion leaders from insti- tutions and organizations worldwide, concentrating on the latest developments in the field. The conference is five days long and held in a remote location to increase the sense of camaraderie and create scientific commu- nities. In addition to premier talks, the conference has designated time for poster sessions and afternoon free The 2026 GRC on Neural Development at Salve Regina University in Newport, Rhode Island USA will bring together scientists who investigate fundamental questions related to nervous system development, using molecular, cellular and organismal approaches. Topics include the genesis of neurons and glia, cell lineages, cell-cell communication including with CNS-resident immune, vascular and fibroblasts, and the assembly of neural circuitry. time, and communal meals allow for informal networking opportunities with leaders in the field. Our excep- tional speakers will address cutting-edge questions including how evolution shaped the emergence and diversi- fication of extant nervous systems, how developmental mechanisms prime the nervous system for future function In line with these broad topics, speakers employ a range of classical and emerging model organisms including flies, frog, fish, mice, ferrets, and non-human primates. They also use state-of-the art human-cell based models like neural organoids. The invited speakers employ broad approaches including: molecular genetic techniques and genomic approaches such as transcriptomic and epigenetic profiling; single cell mRNA sequencing and lineage barcoding; CRISPR-based manipulations and screens; live-imaging and high-resolution microscopy; neuroimaging and human genetics. The meeting will promote extensive exchanges between junior and senior scientists from different career stages, geographic locations and scientific interests. This collegial atmosphere will be fostered through interactions at talks, poster sessions, meals, and informal gatherings during free time. Networking will be promoted with journal editors and members of funding agencies that support research in this field. There will also be many short talks selected from abstracts, which will feature the most exciting recent work by early-career researchers We en- courage applications from researchers across institutions, career stages, countries, and relevant scientific topics, with the goal of having broad participants to enrich the meeting. A GRS is reserved for trainees only, including PhD students and postdocs. This will precede the meeting, and is organized and run by trainees, and will include sessions on related topics along with an invited keynote speaker. and how the nervous system ages under healthy and pathological conditions. .

NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases

Since 1984, the biennial Proteoglycans (PGs) Gordon Research Conference (GRC) has been an essential meeting for PG researchers. Recognized as the leading international forum for PG and glycosaminoglycan (GAG) research it brings together established and new PG researchers in a collegial and scientifically stimulating environment. Important to the meetings success is a history of a collegial atmosphere that fosters the dissemination of unpublished and emerging research that stimulates scientific discussions and collaborations among all attendees. This proposal is requesting partial support for the next PGs GRC, “Frontiers in Basic and Translational Proteoglycan Research to Improve Human Health,” which will be held from June 28th to July 3rd, 2026, and the associated PG GRS entitled, “Integrated Proteoglycan Research to Improve Human Health,” to be held on June 27th - 28th, 2026 at Proctor Academy, Andover, NH. An Executive Committee consisting of former Chairs of PGs GRCs plus organizers of meetings for the international conferences on PGs (ICP) and the International Society for Hyaluronan Sciences (ISHAS) offers input on the conference program. An advisory committee, consisting of expertise in various subfields in proteoglycan research, has been formed. Both committees provide expertise across a broad area, including fundamental, translational, and clinical PG research. The meeting will bring together highly regarded scientists performing impactful PG research and developing new techniques to support proteoglycan research advancement, some of whom will be attending this meeting for the first time. The invited scientists will present the latest findings in fundamental PG research addressing biosynthesis, catabolism, and technological advances in the field. A major focus of this GRC will be highlighting PGs as therapeutic tools and targets. To provide early-stage investigators an opportunity to highlight their research, the meeting program includes short talks during oral session and poster sessions each day. Short talks will be selected from abstracts to be complementary to the theme of the associated oral session. The scientific program aims to present state-of-the-art science to spark scientific discussions and collaborations, leading to the generation of new ideas, innovative research projects, and new grant proposals. The organizers have and will continue to pay careful attention to the participation from different stages in the scientific careers in all aspects of the conference. In the meeting, Dr. Kaori Oshima (MGH), Dr. Rob Ritcher (University of Alabama at Birmingham) and Dr. Paul DeAngelis (University of Oklahoma) will serve as panelists to talk about their experience in overcoming the challenges in academia and discussing different career opportunities for young graduate students and trainees. Attendees of this meeting will be selected by invitation or from the applications submitted online with careful attention. We expect approximately 200 attendees to this conference.

NINDS - National Institute of Neurological Disorders and Stroke

SUMMARY: The 2026 Gordon Research Conference (GRC) on Sleep Regulation and Function, themed “Sleep for the Whole Organism,” will mark the seventh installment of this highly successful series. Over the course of the last decade, sleep research has experienced remarkable growth across a variety of disciplines, spanning molecular biology, systems neuroscience, and mental health. Advances in state-of-the-art technologies have enabled significant progress in our understanding of the neurocircuitry underlying non-REM and REM sleep, wakefulness, the roles of neurotransmitters and neuromodulators, genetic contributions to sleep regulation, and the impact of sleep loss on transcriptional and translational dynamics. The 2026 GRC will build on this strong foundation while expanding into new frontiers. The program will explore sleep as a whole-organism behavior, integrating both brain and body perspectives. In addition to core sessions on sleep regulatory mechanisms and emerging findings from non- mammalian species, the conference will highlight recent findings on sleep’s roles in cognition, consciousness, interoception, and waste clearance from the brain. A session will examine the interplay between sleep and post- infectious disease states, reflecting growing interest in how immune challenges—including long-term consequences of viral infections—impact sleep regulation and homeostasis. The program will further emphasize bidirectional brain-body communication, with discussions on the bi-directional interaction between sleep and peripheral physiology, metabolic state, and systemic signals. Finally, the growing interface between artificial intelligence/machine learning (AI/ML) and sleep science will be showcased, illustrating how advanced computational tools are transforming data analysis, predictive modeling, and mechanistic discovery in the field. This GRC will comprise 50 invited speakers and discussion leaders, poster sessions, in the main meeting. It will be preceded by the GRS, which will provide opportunities specifically for graduate students and post-docs. The GRC and GRS will bring together scientists of all career stages in an interactive and safe environment.

National Foundation on the Arts and the Humanities

The National Endowment for the Arts (NEA), as part of its continuing effort to reduce paperwork and respondent burden, conducts a preclearance consultation program to provide the general public and Federal agencies with an opportunity to comment on proposed and/or continuing collections of information in accordance with the Paperwork Reduction Act of 1995. This program helps to ensure that requested data can be provided in the desired format; reporting burden (time and financial resources) is minimized; collection instruments are clearly understood; and the impact of collection requirements on respondents can be properly assessed. Currently, the National Endowment for the Arts is soliciting comments concerning the proposed information collection through a mixed-methods evaluation of the Creative Forces[supreg]: NEA Military Healing Arts Network Community Arts Engagement Grant Program. The evaluation uses primary and secondary data, and includes interviews, case study site visits, a Participant Survey for individuals who participate in community arts programs, and an Arts Engagement Facilitator Survey for those leading the arts activities. Copies of this ICR, with applicable supporting documentation, may be obtained by visiting www.Reginfo.gov.

National Foundation on the Arts and the Humanities

The National Endowment for the Arts (NEA), as part of its continuing effort to reduce paperwork and respondent burden, conducts a preclearance consultation program to provide the general public and federal agencies with an opportunity to comment on proposed and/or continuing collections of information in accordance with the Paperwork Reduction Act of 1995. This program helps to ensure that requested data is provided in the desired format; reporting burden (time and financial resources) is minimized; collection instruments are clearly understood; and the impact of collection requirements on respondents is properly assessed. Currently, the NEA is soliciting comments concerning the proposed information collection of: Blanket Justification for NEA Funding Application Guidelines and Reporting Requirements. A copy of the current information collection request can be obtained by contacting the office listed below in the address section of this notice.

Rainier Arts Center

In the second edition of the 98118 Fest, we propose to center community partnership while building on our over forty years of experience in live outdoor events. 98118 Fest will take place on August 22, 2026, 12pm-6pm at Columbia Park, located at 3515 S Alaska St, Seattle WA, our community’s “living room,” and at Rainier Arts Center. The festival will showcase performances from a mix of world music and local artists. A pop-up gallery will create opportunities for local artists to sell their work. We will provide soccer- and art-themed activities for kids and families, including face painting, art making, and games. The event will be free and open to the public.

NIA - National Institute on Aging

ABSTRACT IdenƟfying Alzheimer’s disease (AD) in its presymptomaƟc stage can allow early intervenƟon and improve paƟent care. Crucially, the AD-induced amyloid/tau pathology is not limited to hippocampal insult or memory loss, but also impairs /disrupts funcƟonal connecƟons that integrate sensory inputs in the cortex. As these sensory deficits often precede the decline of cogniƟve funcƟon in AD paƟents, understanding their characterisƟc altered funcƟonal connecƟvity and neural hyperacƟvity patterns early in the AD cascade has the potenƟal to yield new diagnosƟc biomarkers or therapies. Similarly, blood flow decline and endothelial dysfuncƟon posited by the vascular hypothesis of AD remains underexplored. While the availability of transgenic AD mouse models has created a unique platiorm for invesƟgaƟng how AD pathogenesis can disturb the neurovascular unit (NVU), design limitaƟons of imaging hardware, e.g. bulky PET, MR or SPECT, that are not developed/opƟmized to probe AD onset, make it unfeasible to image AD pathogenesis at the spaƟal scale of the NVU. Specifically, AD insults the NVU on mulƟple fronts including neural, vascular/blood flow change that span from neurons to cortex-wide brain acƟvity changes, which are modulated with uneven sleep cycle fragmentaƟon/disrupted circadian rhythms. In contrast, preclinical imaging methods are restricted to short duraƟons (< 2 h) due to anesthesia use when imaging a small animal AD model with a device >1000× in size (e.g. PET), and even the state-of-the-art AD studies assess AD-inflicted NVU change only once in every 1-2 months, which substanƟally under-samples the Ɵme course of AD onset. Moreover, since no two brains age the same, subject-specificity can also mask AD-related NVU changes when imaged intermittently. Therefore, new imaging technologies that can generate large neuroimaging datasets and covering mulƟple temporal (days-months), spaƟal (neurons-whole cortex), and modal (neural-vascular) scales are needed to characterize the “funcƟonal fingerprints” of cortex-wide NVU disrupƟon during AD onset. Therefore, we are proposing the development of NeuroCube, which is a miniaturized microscope that will enable mulƟmodal, cortex-wide in vivo imaging >30 days during AD onset in mice. Unlike extant microscopes that lack capacity for long-term operaƟon (<3 h), we will use 3D-prinƟng and fabricate NeuroCube as a robust unit for longitudinal imaging amidst the harsh, jolty condiƟons in an animal enclosure (Aim 1A). To avoid photobleaching, we will use low-light levels, obtain images at low-signal-to-noise raƟos (SNR)/resoluƟon (50 µm), and recover high-SNR/resoluƟon (10 µm) images via a deep learning (DL) backed generaƟve adversarial network (GAN) (Aim 1B). To limit oversized data volumes, we will image in 1-min bursts (0.75 GB) per hour, and curate an imaging dataset that characterize cortex-wide changes of AD, together with gender/age-matched controls (Aim 2). We believe that The NeuroCube and publicly shared in vivo AD datasets will become a vital new tool for the broad AD research community. Moreover, NeuroCubes could be widely useful for interrogaƟng cortex-bound dysfuncƟon in aging and other brain disease.

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT Pathogen transmission via indirect routes such as fomite, waterborne, and airborne transmission are hallmarks of both endemic and pandemic spread. Viruses such as Influenza, SARS-CoV-2, and measles are notable examples, in addition to deadly microbes such as Bordetella pertussis, Mycobacterium tuberculosis, and Coccidioides species. However, the rapid detection and analysis of airstreams as part of biosurveillance, public health monitoring, or epidemiological research remains challenging. Current state-of-the-art methods rely on bulky apparatuses for both the collection and detection of airborne agents; most of these methods are ill suited to rapid response point-of-testing within medical facilities, workplace locals, or public spaces. Further, these technologies are based on bulk Polymerase Chain Reaction (PCR) and Loop-mediated isothermal amplification (LAMP) methods that have limited quantitative accuracy. Thus, more portable and accurate platforms are needed to address the types of rapid response and ubiquitous monitoring that is required to minimize outbreaks in the 21st century. Towards this objective, this grant will address the need for an improved method of airborne pathogen detection through the development of the digital droplet Aerosol Capture & Quantification (ddACQ) system. The ddACQ system consists of two novel technologies, a filter particle array and a droplet buoyancy counter. The filter particle array allows for the capture of airborne pathogens or biological agents and generation of microfluidic droplets when mixed with an oil and water reagent solution. A phone-powered heat block then drives a one-step isothermal digital droplet reaction. Digital techniques have several key advantages over classical quantitative PCR and LAMP techniques, namely single molecule detection and direct quantification without a standard curve. Finally, the droplet buoyancy counter allows for smartphone based read out of the reaction immediately at the testing site in under an hour. Together, the innovations within and implementation of the ddACQ system represents a novel application of microfluidic principles and an enabling technology for both pathogen transmission research and public health monitoring applications.

NIDA - National Institute on Drug Abuse

Project Summary: HIV infection and cocaine use are comorbid conditions that can exacerbate each other's harmful effects, as ART is not sufficient to fully suppress HIV transcription or prevent latency reactivation. HIV gene products (RNA and proteins) greatly contribute to perpetual immune activation and inflammation throughout the system, primarily in the central nervous system (CNS) of people with HIV (PWH). Additionally, viral latency, the main cause of HIV persistence, is also largely regulated at the transcriptional level. Therefore, defining all the mechanisms that control HIV transcription is essential before utilizing them therapeutically to limit HIV persistence and associated comorbidities, such as neuroinflammation, which is prevalent even in well-controlled PWH. DNA breaks are a common occurrence during the transcription of genes, which are required to be repaired via transcription-coupled repair (TCR). Without TCR, during transcription of a gene, breaks in the template DNA cause frequent RNAPII pausing or degradation, which halts transcription. Interestingly, upon cocaine exposure to microglia, we noted both the increased DNA-dependent protein kinase (DNA-PK) activity and corresponding enhanced HIV transcription and replication. Additionally, we found that DNA-PK knockdown results in the dissociation of TCR machinery from LTR, showing a direct role of DNA-PK. However, in microglia, the major HIV reservoir in the CNS, the impact of DNA-PK-mediated TCR during HIV transcription in the context of ART and cocaine, and the potential therapeutic reversal using clinically tested DNA-PK inhibitors (DNA-PKi), remains largely unexplored. This study aims to address this critical knowledge gap, using brain organoids harboring microglia. Together, these facts offer a strong premise for the hypothesis that DNA-PK plays a crucial role during TCR and neutralization of negative factors in relieving RNAPII pausing during HIV transcription, and cocaine further supports these effects by stimulating both the level and activity of DNA-PK; however, clinically tested DNA-PKi can reverse this process, limiting viral load and rebound after ART interruption. Aim 1 will investigate the role of cocaine-induced DNA-PK in relieving RNAPII pausing via TCR in brain organoids and iPSC-derived microglia +/- ART. Aim 2 will define the impact of DNA-PK mediated regulation of negative transcription factors (NFs) during RNAPII pause-release. Aim 3 will test the efficacy of clinically tested DNA-PKi in blocking HIV transcription and viral rebound upon ART interruption in the context of cocaine +/- ART in brain organoids. The proposed high-risk/high-payoff exploratory study with great translational potential is closely aligned with the main objective of this FOA: 1) we propose to develop new tools and techniques in our lab - DNA curtain methodology/assay and human brain organoids harboring microglia; 2) define a novel mechanism, DNA-PK- mediated TCR, in regulating HIV transcription, latency, and rebound in the context of cocaine+/- ART.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY HIV-1 establishes life-long infection that requires continual antiretroviral therapy (ART) to suppress virus replication. Although long-acting ART promises to improve treatment adherence, a therapeutic countermeasure for suppressing HIV-1 infection without lifelong treatment is needed. This type of HIV cure strategy is called a functional cure. In preliminary studies, we designed a series of immunogens that elicit serum nAbs against heterologous viruses in macaques. The nAbs target the second variable region (V2) Apex on HIV-1 envelope, with binding orientations similar to known human V2 Apex broadly nAbs (bnAbs). This B cell targeting countermeasure is the main innovation of our study. Furthermore, we developed an integrase-deficient lentiviral vector (IDLV) that delivers the viral gag gene to elicit specific CD8 T cells. Induction of these CD8 T cells suppressed viremia to undetectable levels in macaques. Our conceptual innovation is to combine both successful countermeasures together to potently and durably control viremia. The objective of this study is to sustainably suppress HIV viremia by combining a CD8 T cell countermeasure that controls viremia with a B cell countermeasure that elicits neutralizing antibodies (nAb) that are active against many heterologous viruses. The proposal has three specific aims. First, to determine the immunogenicity of the combination T cell and V2 Apex nAb-inducing countermeasure in ART-suppressed, SHIV-infected macaques by comparing the neutralization breadth of serum and monoclonal Abs, as well as CD8 T cell cytokine production and inhibition of virus-infected cells among a mock-treated group, the countermeasure treated group, and previous groups of uninfected macaques. Second, to demonstrate sustained viral suppression without ART by the administration of the therapeutic countermeasure in chronically SHIV-infected macaques by assessing changes in CD4 T cells and virus nucleic acid over time following ART cessation. Mechanistic studies will be done in macaques to show CD8 T cell and V2 apex nAb contributions to viral suppression. Third, to determine the impact of ART on the frequency of V2 Apex-specific B cells in people living with HIV-1 (PLWH) using a 10X Genomics BEAM-seq sequencing and AI/ML approach to identify V2 Apex B cells in PLWH before and during ART. The impact of this study is that it will define a therapeutic countermeasure that can permanently suppress viremia, taking the first steps toward a functional cure for the nearly 40 million people currently living with HIV-1.

NIAID - National Institute of Allergy and Infectious Diseases

Project summary Herpes simplex virus (HSV) establishes latency in ganglionic neurons of the peripheral nervous system. Latent HSV can later reactivate, causing recurrent disease and possible transmission to new hosts. Current anti-HSV therapy is inadequate, in that it does not eliminate latent HSV, and thus is only suppressive rather than curative. We developed a therapeutic approach based on gene editing using HSV-specific meganucleases. We showed that intravenous (IV) administration of adeno-associated virus (AAV) encoding anti-HSV-1 meganucleases can eliminate up to 97% of latent HSV DNA from dorsal root ganglia in mouse models of latent HSV-1 genital infection. We also demonstrated that this reduction in ganglionic viral load led to a corresponding reduction of viral shedding from treated vs. control mice. This approach offers the potential for a durable means of controlling latent HSV infection and subsequent reactivations, or even achieving a functional cure. In the R21 phase, we propose to extend our work to target HSV-2, and to determine whether IV or localized intrathecal (IT) administration is the optimal route. In the specific aims of the R33 phase we plan to address simultaneously several outstanding issues regarding both HSV biology and the safety and efficacy of in vivo gene therapy that are critical for clinical translation of our work. R21 Phase: Specific Aim 1. Evaluate IT vs. IV delivery of AAV/meganuclease therapy as a means to reduce AAV dose, minimize systemic exposure, and avoid pre-existing/induced anti-AAV immunity. We will evaluate the AAV biodistribution, antiviral efficacy, and dose response after IT vs. IV administration, and the doses at which toxicity occurs. We will also evaluate the ability of IT-delivered AAV to avoid neutralizing antibody present in serum, and whether IT administration will allow re-dosing of AAV. R33 Phase: Specific Aim 2. Compare the natural history of ganglionic HSV load and peripheral viral shedding in latently infected mice after IT or IV meganuclease therapy vs. untreated control animals. We will perform long-term studies of the ganglionic viral load and the frequency and quantity of peripheral shedding in control vs. AAV-meganuclease treated animals. These studies will shed light on the stability of reservoirs, the relationship of ganglionic viral load reductions with the frequency and quantity of viral shedding, and provide new insights into possible HSV re-seeding of ganglionic reservoirs after viral reactivations. R33 Phase: Specific Aim 3. Determine the host genomic consequences of AAV/meganuclease therapy, and compare to the effects after CRISPR/Cas9 exposure. We will perform an unbiased evaluation of genomic disruptions after our meganuclease therapy, and directly compare with CRISPR/Cas9 approaches, using the state-of-the-art techniques for the detection of off-target events, including GUIDE-seq, improved DISCOVER-Seq+, and analyses for the insertion of AAV vector (ITR-Seq) and HSV DNA (hybridization capture coupled with next generation sequencing) into the host genome.

OD - NIH Office of the Director

PROJECT SUMMARY This proposal seeks to acquire a RH96 Octet – a next-generation, high-throughput bio-layer interferometer (BLI HTS) for biomolecular interaction studies. BLI HTS is a “96-channel” instrument that allows quantitative measurements of protein-protein and protein-small molecule interactions of up to 96 samples simultaneously. It uses small sample volumes, and the ease of use allows researchers with broad scientific expertise to use the instrument for high-throughput screening of interactors such as proteins, antibodies, and small molecules. There is an urgent unmet need for this instrument, as there is no high-throughput BLI instrument in the entire Midwest region. We have identified 14 NIH-funded researchers whose work and progress is severely limited due to the absence of this instrument. They often travel to out-of-state institutions or use the 2-channel BLI instrument currently available at Northwestern; clearly, neither option is a long term solution. The 2-channel instrument is not amenable to high-throughput data collection and requires large sample volumes, impeding drug discovery and screening efforts. Moreover, the data collection on the 2-channel is tedious even for single protein-protein interaction studies when testing multiple concentrations. The proposed instrument will address a significant gap in the instrumentation available at Northwestern University and will be beneficial not just to the Northwestern community but the entire Midwest area. We propose to add the BLI HTS to the Northwestern High-throughput Analysis Laboratory, which houses several instruments for high-throughput screening and has full-time staff with the technical expertise to manage and operate the instrument. We anticipate that at least 14 research groups from 6 departments across the College of Arts and Sciences, the Feinberg School of Medicine and the McCormik School of Engineering will utilize this equipment. The availability of this state-of-the-art instrument at Northwestern will be particularly important for drug development efforts and will advance a range of studies aimed at creating therapeutic and diagnostic tools for various human diseases, including cancer, metabolic disorders and neurodegeneration.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

In Vietnam, adolescent and young men vulnerable to HIV through sexual behaviors are among those most affected by the infection, with an HIV prevalence that quadrupled from 3% in 2011 to 13% in 2020. More than 20% of Vietnamese young men living with HIV had moderate-to-severe depression and anxiety symptoms. These youths experienced extensive stigma related to their HIV status and sexual behaviors. There is a dearth of youth-friendly mental health services in Vietnam where there is less than one psychiatrist per 100,000 people. Project YES+ is an intervention integrating two evidence-based interventions, Project YES! and Self-Help+ to improve mental health, stigma, and HIV outcomes among youth living with HIV in Zambia (5R01TW012411). Youth Engaging for Success (Project YES!) is an HIV clinic-based peer mentoring CDC-designated intervention that successfully decreased HIV self-stigma and increased viral suppression. Self-Help+ is a group-based lay-delivered program endorsed by WHO that effectively prevents the onset of mental disorders and reduces mental health symptoms in different cultures. We propose to adapt Project YES+ for adolescent and young men living with HIV in Vietnam to create To Hieu (I Understand) and to pilot test the adapted intervention. The specific aims are to (1) Adapt Project YES+ to create To Hieu to improve mental health and reduce internalized HIV stigma for adolescent and young men living with HIV in Vietnam and (2) Examine acceptability and feasibility of To Hieu among adolescent and young men living with HIV through a pilot randomized controlled trial. In Aim 1, the adaption will follow the 8-step ADAPT-ITT framework.38 We will conduct in-depth interviews with adolescent and young men living with HIV (N=20) to explore preferences for the core components and formats of To Hieu. We will hold a human-centered design workshop to engage adolescent and young men living with HIV in co-design activities to refine To Hieu. In Aim 2, we will recruit 80 adolescent and young men living with HIV with depression or anxiety symptoms at two HIV clinics in Hanoi, Vietnam and randomize them 1:1 into two arms. The intervention arm will receive To Hieu in 4 months, while the control arm will receive standard of care at the clinics. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework will guide the measurement of the outcomes. We will calculate participation rates of participants (Reach) at baseline. We will assess acceptability through the Client Satisfaction Questionnaire and feasibility through intervention attendance (Adoption) at 4 months. Depression, anxiety symptoms, internalized HIV and sexual stigma, ART adherence and viral suppression of participants will be evaluated at baseline, 4 months and compared between groups (preliminary Effectiveness). We will conduct exit interviews with participants, youth peer mentors and HIV providers (N=30) to explore acceptability, feasibility (Implementation) and sustainability (Maintenance) of To Hieu. This research will build local capacity and develop networks for collaborative research on mental health and stigma among adolescent and young men living with HIV between Vietnam and the US.

NIMH - National Institute of Mental Health

ABSTRACT Despite advancements in antiretroviral therapy (ART), only 65% of people with HIV (PWH) in the United States (US) achieve viral suppression, with significant differences observed across sociodemographic groups. Long- acting injectable ART (LA ART) has the potential to address challenges associated with daily oral ART, but its adoption has been slow, with only 1.44% of PWH—approximately 15,000 individuals—on LA ART after two years of availability. This low uptake highlights persistent barriers and mirrors challenges seen with pre-exposure prophylaxis (PrEP), including slow adoption and differences in awareness, interest, and use. Further research is needed to understand factors shaping PWH decisions regarding innovative ART therapies. PWH face complex considerations when selecting treatment regimens, including regimen characteristics, psychosocial factors, and logistical barriers. While these factors are well-studied for oral ART, less is known about how PWH weigh these considerations for LA ART. This study will use advanced quantitative methods, including latent class analysis (LCA) and structural equation modeling (SEM), to identify treatment preference typologies and examine how individual, provider, and clinic-level factors shape ART preferences, addressing critical gaps in knowledge. Guided by the Consolidated Framework for Implementation Science 2.0, this project has two aims: 1) Identify HIV treatment regimen consideration patterns (classes) and assess the association between class membership and sociodemographic characteristics among PWH; and 2) Examine how patient (treatment regimen preference patterns), provider (trust, shared decision-making) and clinic-level factors (quality of clinical care) influence ART preferences among PWH. Findings will inform multilevel interventions to improve outcomes. Moreover, the identification of patient treatment typologies will enable providers to align discussions and interventions with the unique preferences of PWH. To achieve these aims, the proposed training plan focuses on developing advanced skills in LCA and SEM, deepening expertise in implementation science frameworks, and applying these findings to design multilevel interventions. Through mentorship, coursework, workshops, and applied research, the applicant will gain the knowledge and experience necessary to become an independent behavioral and implementation scientist, equipped to address access challenges in the evolving landscape of HIV treatment. This NRSA award will provide the necessary mentorship and resources to achieve these goals.

NIAID - National Institute of Allergy and Infectious Diseases

7. PROJECT SUMMARY/ABSTRACT Globally, approximately 300 million live with chronic HBV (CHB) and 40 million people live with HIV. Due to shared transmission routes, approximately 10% of people with HIV (PWH) also live with HBV (PHBV). Importantly, HIV/HBV coinfection is associated with increased mortality. Like HIV, while effective HBV treatments are available, there is no cure for HBV. Hepatitis B surface antigen (HBsAg) loss, the definition of HBV functional cure, decreases incidence of hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD), yet is not easily attained with current therapy. As such, the development of novel HBV therapies, aiming for HBV functional cure, is rapidly advancing. HBV functional cure research has become a scientific priority of the NIH, industry, academia, and the community with over 50 clinical trials and compounds in development. Interestingly, HBV functional cure occurs more often in PWH/PHBV, making this an ideal cohort in which to study HBV curative therapies. Despite the pace and volume of HBV cure research, there is little knowledge about patient and provider perspectives on key HBV clinical trial approaches – unlike in HIV cure research, where over a decade of experience has informed priorities. One of the key clinical trial–related questions is whether and how to implement HBV treatment discontinuations, which will be necessary to study the efficacy of curative and finite HBV novel therapies. This will pose specific challenges in PWH/PHBV, such as the heightened likelihood of rebound hepatitis and the ongoing need for HIV antiretroviral treatment (ART). There is a notable lack of data regarding both patient and provider knowledge and priorities concerning this pivotal research phase, including questions of whether HBV treatment discontinuations are desired, the duration of discontinuation, or how to manage it. Similarly, there are limited data on trial design elements such as type of novel therapies, timing of therapy initiation, and willingness to participate in HBV cure trials. These knowledge gaps remain key hurdles to advancing effective, safe, and acceptable HBV cure strategies. Data from this application will be crucial for the development of HBV clinical trials attractive to PWH/PHBV and PHBV. Our proposed work will inform outreach, recruitment, consent, and retention of participants in future HBV clinical trials. To this end, our Specific Aims are as follows: Aim 1 will explore priorities of PWH/PHBV, PHBV and providers around key aspects of HBV clinical trials including HBV treatment discontinuations, choice of novel HBV agents, and trial participation using in-depth interviews. Aim 2 will quantify priorities of PWH/PHBV and PHBV around these same trial elements through a national U.S. survey. Aim 3 will develop ethical considerations and obtain feedback on provider- and patient- facing materials in collaboration with key stakeholders. Together, our three aims will clarify therapeutic advancement priorities and guide the ethical design of future innovative HBV clinical research with significant implications for population health. This work is directly relevant to the health of all Americans, as it addresses chronic disease management, co-morbidities, and the reduction of long-term burdens on the healthcare system.

NIDA - National Institute on Drug Abuse

Project Summary Multimodal data have been generated and collected as part of HIV care delivery and research including, but not limited to, structured data and unstructured data in electronic health records (EHRs), claims data, pharmacy records data, imaging data, omics data and other molecular biomarker data. Such rich data offer great opportunities for harnessing the transformative power of artificial intelligence (AI) and machine learning (ML) to enhance personalized clinical decision support and address unmet needs in HIV prevention and care. Multimodal AI that can integrate multiple modalities of data encountered in clinical practice has been shown to yield superior performance over simpler, unimodal models in various disease areas outside of HIV. However, multimodal biomedical data are typically complex and heterogeneous, and are fraught with missing data and other sources of biases. For example, patients with less access to healthcare or lower socio-economic status tend to have more incomplete data in their EHRs. Thus, advancing multimodal AI for HIV applications faces significant technical challenges in the training, validation, and implementation, including, but not limited to, quantifying the dimension of heterogeneity, identifying interconnections, and addressing missing data. Another major barrier in advancing multimodal AI in HIV applications is that multimodal data in HIV are typically not publicly available. Our project seeks to address these and other challenges through three specific aims. In Aim 1, we will develop novel accurate, efficient and unbiased multimodal AI models for HIV care and prevention. In Aim 2, we will adapt and create causal knowledge graphs to enhance interpretability for applications in HIV care and prevention. In Aim 3, we will develop synergistic integration of knowledge graphs and multimodal AI models for more precise model and increased usability in HIV care and prevention. We will train and test the proposed multimodal AI models and knowledge graphs using multimodal data from the Veteran Health Administration, the largest integrated health system in the US, and the Veteran Aging Cohort Study for three important use cases in HIV prevention and care, namely, 1) identification of HIV patients at risk of medication non-adherence and/or loss to care; 2) prediction of complications of HIV patients; and 3) identification of patients at high risk of HIV infection. Our model development will be guided by ethical principles to ensure data privacy, security, and transparency. We will adopt a human-centered approach that seeks valuable inputs from and meaningful engagements with key stakeholders informed by the theory of Participatory Action Research. Once successfully completed, our project is expected to advance the state-of- the-art multimodal AI and knowledge graphs that can be applied/adapted to other use cases in HIV and transform HIV care and prevention.