Grants

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Pseudomonas aeruginosa (Pa), a ubiquitous, environmental Gram-negative bacterium, is a leading cause of healthcare-associated infections worldwide resulting in >400,000 deaths annually. Treatment is challenging because Pa harbors a wide array of intrinsic and acquired antibiotic resistance mechanisms. Of all invasive infection types, Pa bloodstream infections (PABSI) have very poor patient outcomes and bloodstream infections secondary to Pa are more lethal than those of any other bacterium. The reasons for this are unclear. Recently, we were the first to show that during bloodstream infection, Pa traffics to the liver, expands in the gallbladder, and is excreted in the gastrointestinal (GI) tract. Additionally, we showed that the gallbladder was the critical organ that facilitated high level Pa excretion and promoted transmission. To survive in the liver and gallbladder and establish a niche in the GI tract, Pa must be adapted to thrive in bile, a complex fluid produced by the liver, concentrated in the gallbladder and excreted into the GI tract. Bile is composed of bile acids and salts, cholesterol, proteins, and lipids that are inherently antimicrobial. Resisting bile exposure is universally critical for pathogen success in the GI tract and the GI-resident bacterial population serves as a reservoir for invasive Pa infections. To dissect the mechanisms by which Pa resists bile exposure, this project will explore an exciting, newly identified bile resistance sodium-hydrogen antiporter, and, by expanding our bile resistance analysis of multiple Pa strains, identify shared (common) and strain-specific bile resistance pathways. The approach of Aim 1 is two-fold. First, we will investigate the role of the sodium-hydrogen antiporter, shaA-F, in bile resistance. This operon was identified by an early comparative transposon-insertion (INSeq) experiment as critical for bile resistance. Additionally, we will characterize the role of each protein in the sha operon in GI carriage and pathogenesis. Second, to complement genetic approaches, RNA sequencing will be utilized to profile global bacterial transcriptional responses to bile, with an emphasis on understanding if and how sha is regulated by bile exposure. Aim 2 will deploy comparative transposon insertion sequencing (INSeq) across additional representative Pa strains to identify additional shared and strain-specific genes necessary for bile resistance. Following gene deletion, both shared and strain-specific targets will be assayed in vitro and in vivo to determine their impact on bile resistance and Pa pathogenesis in a model of PABSI. The proposed work will produce the first multi-strain comparative analysis of Pa responses to bile exposure by deploying a powerful combination of genetic and transcriptomic approaches. As bile resistance is critical for the establishment of pathogens in the human GI tract and bile exposure increases antimicrobial resistance in many pathogens, we believe that pathways identified by this proposal present exciting new targets for the development of antimicrobial agents to treat Pa infections.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY/ABSTRACT Severe asthma exacerbations are a major cause of intensive care unit admissions in children, leading to significant healthcare burden in the United States. While there are clear guidelines for first-line treatment, the benefit of non-invasive ventilation (NIV) remains unknown for children who fail to respond to the first-line treatment. Bilevel Positive Airway Pressure (BPAP) is a type of NIV that may be an important second-line therapy for managing severe asthma exacerbations in children but has not been sufficiently studied. Our ultimate goal is to determine if early, emergency department (ED) initiation of BPAP for at least two hours decreases critical care resource use and is safe in children with severe asthma exacerbations. As a step toward this goal, the aims of the proposed study are: Specific Aim 1: To develop a consensus-derived protocol for ED BPAP administration and the use of asthma therapies for children with severe asthma exacerbations among sites that may participate in the definitive trial and among whom practice variation exists. We will use a consensus decision-making model to create a protocol for ED BPAP use and other asthma therapies. Specific Aim 2: To determine a primary outcome measure for the definitive study of early ED BPAP in children with severe asthma exacerbations that reflects critical care resource use. We will use a Delphi method to gain consensus across sites, with measures to be evaluated including, but not limited to: intensive care unit (ICU) admission rate, ICU length of stay, duration of BPAP use, and duration of continuous albuterol. Specific Aim 3: To demonstrate the feasibility to enroll sufficient patients, adhere to an ED protocol for BPAP use for at least 2 hours, and complete other key study procedures for a subsequent multicenter randomized trial comparing early ED BPAP to no BPAP for children with severe asthma exacerbations. We will conduct a feasibility RCT that aims to mirror a subsequent multicenter trial in design, population, intervention arms, procedures, and outcomes assessed. The study will be conducted within the Pediatric Emergency Care Applied Research Network (PECARN). The results will inform the definitive trial of early use of ED BPAP in children with severe acute asthma. The definitive RCT will potentially have a tremendous benefit to both individual patients and the healthcare system.

Somali Community Services of Seattle

Somali parents will gain job readiness and computer skills training in a state-of-the-art computer lab. Aging computers will be replaced with new equipment.

Neighborhood House

Bilingual handbooks in Amharic, Chinese, Oromo, Somali and Vietnamese will be developed and distributed to help limited English speakers apply for jobs online at major employers’ websites. This is a partnership with Asian Counseling & Referral Service

Personnel

RFP - Request For Proposal

NYC Department of Cultural Affairs

Billie Holiday Theatre, Inc.

VETERANS AFFAIRS, DEPARTMENT OF.VETERANS AFFAIRS, DEPARTMENT OF.NATIONAL CEMETERY ADMIN (36C786)

Biloxi National Cemetery Expansion and FCA Deficiencies

NSF

With the support of the Chemical Catalysis Program in the Division of Chemistry, Professor Steven Diver of the University at Buffalo, the State University of New York, is studying new catalysts embedded in cage-like frameworks for selective catalysis. These catalysts are hybrid molecules, combining the best attributes of enzymes with the high performance and wide chemical repertoire of small molecule (molecular) catalysts. This new design will enable selective reactions, which will have impact in a number of different fields such as organic synthesis, polymer chemistry and pharmaceutical chemistry related to drug discovery. In addition to these applications, there are broader societal impacts from this research activity. The research activity will prepare students for careers in chemistry and chemistry related fields and advances sustainability concepts in synthesis. The use of these new selective catalysts has the potential to vastly improve efficiency and provide new synthetic possibilities which will streamline the synthesis of bioactive molecules. This may in the long run accelerate the drug discovery process and reduce the cost of medicines for the American public. With the support of the Chemical Catalysis Program in the Division of Chemistry, Professor Steven Diver of the University at Buffalo, the State University of New York, is studying new bimacrocyclic catalysts for size-selective reactions catalyzed by the earth abundant metals, Mn, Co, Ni and Co. The key objective is the design and modular synthesis of multidentate ligands, whose macrocyclic size can be easily and predictably adjusted. Within two ligand classes proposed, the macrocyclic design will create or enhance enantioselectivity, allowing molecular recognition in terms of both steric size and chirality. New catalysts that can manage reactivity through site selectivity will allow synthesis to be carried out differently, without protecting group manipulations to select which functional group should react. This will greatly increase efficiency and decrease costs, waste and environmental impact. Size-selectivity based on the bimacrocyclic ligand will allow members of the same functional group to be distinguishable from each other, enabling site selectivity. This new approach to chemical synthesis would change the way a synthesis can be conducted, reduce the need or reliance on protecting groups and would vastly increase efficiency. These new macrocyclic catalysts will be used to achieve selectivity in high value reactions such as alkene epoxidation, cross coupling and alkene hydrofunctionalization. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

City of Richmond

Bin 415 LLC

Big-Brained Superheroes Club

Provide a Science, Technology, Engineering and Math (STEM) program for youth from Yesler Terrace, ages 8 and up. Youth will introduce the Big Brain Binary Counter to people throughout the city, set up a public code repository and produce tested open-source development documentation

NYC Department of Cultural Affairs

Bindlestiff Family Variety Arts, Inc.

BINGHAMTON REGIONAL SUSTAINABILITY

Binghamton Community Power Phase II: Empowering Residents of Environmental Justice Neighborhoods with Knowledge about their Home�s Energy Systems and Tools to Advocate With Officials and Utilities. This project will help residents understand how the energy systems in their homes work, provide guidance to navigate energy improvement programs, advocate for themselves with the utility, and provide an understanding of clean energy career opportunities.

BINGHAMTON REGIONAL SUSTAINABILITY

This project will help residents understand how the energy systems in their homes work, provide guidance to navigate energy improvement programs, advocate for themselves with the utility, and provide an understanding of clean energy career opportunities.

BINGHAMTON REGIONAL SUSTAINABILITY

This project will help residents understand how the energy systems in their homes work, provide guidance to navigate energy improvement programs, advocate for themselves with the utility, and provide an understanding of clean energy career opportunities.

Market NY - RC5 - EDF

Binghamton Culinary Tourism Alliance Working Capital

EAP

Binghamton LDC EAP Center 16-17

EAP

Binghamton LDC Entrepreneurial Assistance Program Center 17-18

Volunteers Improving Neighborhood Environments Inc.

For repair of urban farms that were damaged by the flooding of Tropical Storms Irene and Lee, and expansion of the farms to benefit community residents.

Volunteers Improving Neighborhood Environments Inc.

For repair of urban farms that were damaged by the flooding of Tropical Storms Irene and Lee, and expansion of the farms to benefit community residents.

NSF

A central goal in neuroscience is to understand how networks of neurons process information to generate behavior. Recent advances in imaging have produced detailed maps of brain networks, including individual connections (synapses) between neurons. Yet it remains unclear how to best use these maps to build accurate models of how the brain works. This project will investigate whether neurons integrate information in a surprisingly simple way: by treating all incoming signals equally, regardless of where they land on the neuron's branching input structure, called dendrites. If this “dendritic democracy” proves to be a common feature, it would allow researchers to streamline complex brain models while preserving their accuracy, vastly enhancing computational speed and paving the way for energy efficient, brain inspired AI biotechnologies. The project will also include a strong educational component, integrating findings into high school neuroengineering modules and providing summer research fellowships for students. High school students will use low-cost tools and real behavioral data to explore how brain circuits drive behavior, gaining early exposure to neuroscience, computation, and machine learning. In addition to its scientific contributions, the work will result in publicly available simulation tools, machine learning pipelines, and curriculum materials that support computational neuroscience and STEM education. This project will evaluate the extent to which dendritic democracy, defined as the passive equalization of synaptic input effectiveness across dendritic locations, is a generalizable feature of Drosophila melanogaster neurons and how it influences the interpretation of electron microscopy (EM)-derived connectome data. The investigators will use detailed multicompartment neuron models, constrained by EM morphology and experimentally measured passive properties, in combination with in vivo electrophysiological validation. A central question is whether synapse number alone is sufficient to predict postsynaptic responses during realistic spatiotemporal activation, or whether accurate modeling requires incorporating dendritic structure and synapse location. The project aims to clarify when simplified neuron models provide sufficient explanatory power and when more complex representations are required. To address this, the investigators will apply machine learning approaches to explore the parameter space supporting dendritic democracy and will develop complementary analytical tools rooted in biophysical theory. These tools will be used to evaluate neurons from multiple brain regions, producing general principles to guide modeling strategies for EM datasets in both Drosophila and other species. This project is co-funded by the Directorate for Biological Sciences Activation Program in the Neural Systems Cluster of the Division of Integrative Organismal Systems and by the Division of Emerging Frontiers. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

Microbial communities living on and around plants influence plant growth and health in positive or negative ways, but the factors that determine these outcomes are not well understood. Gaining insight into how these microbial communities function is essential for improving crop performance, reducing losses to disease, and supporting food security. This project will investigate how the composition and characteristics of root-associated microbial communities shape plant development and health. By combining biology, engineering, and machine learning, the team will identify bacterial strains that, when assembled into communities, promote plant growth and help protect against disease. These findings will support the development of beneficial microbial products that enhance crop performance and reduce agricultural inputs. The project will also train undergraduate and graduate students, provide summer research opportunities for high school students, and support K–12 science education through a training workshop for local teachers on plant microbiomes and related science and engineering topics. Although plant microbiomes play a major role in influencing plant outcomes, we have a poor understanding of the causal links between the functional properties of microbiomes and plant host phenotypes. This project will use a well-characterized collection of plant-associated bacterial strains to construct a variety of synthetic communities and study how specific combinations affect plant growth and pathogen resistance. DNA barcoding will enable precise tracking of microbial colonization, and high-throughput imaging will capture plant phenotypes over time. The project will support the development of machine learning models to analyze these data and identify community features that optimize plant performance by balancing growth and health outcomes. It will also investigate the genetic basis of beneficial microbial effects using mutagenesis and functional screening. Together, these efforts will uncover how microbial communities and their functions influence plant outcomes, while generating new experimental and computational tools for plant biology and microbiome engineering. The findings will guide the development of beneficial microbial communities for crops and support continued innovation in agriculture. This project is supported by the Systems and Synthetic Biology Cluster of the Division of Molecular and Cellular Biosciences, the Plant Biotic Interactions program of the Division of Integrative Organismal Systems, and the Emerging Frontiers Division in the Directorate for Biological Sciences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

In plants, like corn, leaf aging (also known as senescence) is accompanied by regular cellular and physiological changes. Some of these changes are outwardly visible--like drying, loss of green color due to reduced photosynthesis, and browning under drought. Other changes are not obvious to the naked eye but are very important for the plant. One such change involves recycling of nutrients from the aging leaf to developing parts of the plant, such as kernels on the ear. The timing of senescence is crucial—too early results in low grain yield. By contrast, plants that delay senescence and stay green longer into the growing season tend to yield more grain. Exactly what controls the timing and the many steps in senescence is not clearly known. This project will develop new ways to measure corn traits during aging, discover causative genes, and apply computational methods like artificial intelligence to understand how nutrient recycling in plants can improve agricultural outcomes. The project will also provide interdisciplinary training for undergraduate and graduate students, postdoctoral researchers, and high school teachers to help inspire and prepare the next generation of scientists, ultimately strengthening capacity in plant biology, data science, and agricultural biotechnology. This project aims to uncover the genetic, metabolic, and regulatory mechanisms that govern leaf senescence and nutrient remobilization in maize—processes that directly impact grain quality, nitrogen use efficiency, and overall crop productivity. Despite their agronomic importance, the molecular drivers of senescence remain poorly understood in cereals. To address this gap, high-resolution, time-series datasets will be generated across a genetically diverse maize panel, capturing physiological traits, metabolite profiles, transcriptomes, and chromatin accessibility. Single-cell assays will add spatial resolution to senescence-related transcriptional and chromatin changes. These datasets will be integrated using artificial intelligence tools, such as large language models, and machine learning to identify causal genes, regulatory elements, and metabolite-phenotype associations. Top candidate genes will be functionally validated using gene-editing technologies to confirm their roles in regulating senescence and nutrient allocation. The resulting insights will inform breeding and biotechnological strategies to enhance nitrogen use efficiency, reduce fertilizer inputs, and improve resilience to abiotic stress. This project is co-funded by the Division of Integrative Organismal Systems Plant Genome Research Program and by the Division of Emerging Frontiers, both in the Directorate for Biological Sciences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

How do you remember where you have been or how to get from one place to another? Although animals are very good at these forms of spatial memory, the mechanisms remain poorly understood. Understanding these mechanisms is important, because the skills they control are crucial for animal survival. Such skills also have practical applications for designing human devices. For example, a robot vacuum should remember where it has and has not cleaned, and it should find its way back to the charger. Yet, remarkable as they may seem, such smart tools are much less capable than animals at spatial memory-dependent tasks. This project seeks to better understand how animals perform such tasks and translate that understanding into advances in artificial intelligence. Importantly, this research focuses on a previously overlooked strategy that animals, rats in this case, often use when navigating: they take a break from doing the navigation task at hand and change posture, seemingly to absorb information from a wider or different angle. Preliminary studies showed that animals that engage in this additional posture shift perform better in navigation tasks. In this project, experiments will be used to determine what information animals absorb during the shift in strategy and how neural activity in the hippocampus--a brain region critical for spatial navigation--changes in association with the behavioral strategy. In combination with the experimental studies, computational models and machine learning will be used to understand the biology while advancing artificial intelligence systems for use in a wide range of devices to make daily lives of humans better. The project will also provide opportunities for students at all levels to gain training at the intersection of neurophysiology and machine learning/artificial intelligence. Spatial memory is well known to depend on intact hippocampal function. Yet, the hippocampus's role in spatial memory encoding remains unclear. The investigators recently found that blocking hippocampal activity during rearing (when rats stand on their hind legs) impairs spatial memory, identifying rearing as a key behavioral epoch for memory encoding. The discovery that rearing is key for hippocampal-dependent spatial memory encoding is significant, as it expands the very short list of behavioral markers linked to critical hippocampal functions. This project builds on this finding by determining: 1) what information rearing provides to update the cognitive map, 2) whether other behaviors elicit similar hippocampal dynamics and if blocking activity during these behaviors affects memory, and 3) whether rearing indicates curiosity-driven information foraging. Addressing these unknowns has implications for multiple fields of study. First, by examining how new information acquired during rearing is integrated into existing cognitive maps, the project uncovers principles of continual learning through active sampling. Second, by investigating what other behaviors elicit hippocampal dynamics like rearing, the project may identify additional exploratory behaviors that support spatial memory and connect them to underlying neurophysiological mechanisms. Third, by testing whether rearing reflects curiosity-driven information foraging, the project evaluates normative models explaining when and why rats choose to rear. The investigators address these questions using a combination of high-density electrophysiology, closed-loop optogenetics, behavioral analysis, machine learning and computational modeling. This project is supported by the Directorate of Biological Sciences Division of Integrative Organismal Systems Neural Systems Cluster Modulation Program and by the Division of Emerging Frontiers. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH

Intervertebral disc degeneration is strongly implicated as a cause of low back pain. Over a 10 year period, more than 130,000 active service members received diagnoses of disc degeneration, with annual incidence rates more than doubling during this time. Current treatment approaches are mostly conservative, and in severe cases, patients may undergo surgical procedures such as spinal fusion, which do not maintain or restore native tissue structure or mechanical function. The earliest manifestations of disc degeneration typically occur in the central nucleus pulposus (NP), where decreasing proteoglycan content and hydration compromise the ability of this tissue to transfer compressive loads, leading to progressive structural breakdown of the entire intervertebral joint. Cells within the NP lose their anabolic phenotype and begin to show a fibrotic phenotype, resulting in the fibrotic transformation of the NP extracellular matrix. Combined, this proteoglycan loss and progressive fibrotic NP remodeling pushes the entire disc tissue towards a degenerative state. The NP is therefore a key target for regenerative therapies, particularly early interventions addressing mild to moderate severity degeneration. Arresting and reversing this fibrotic transition is key to restoring healthy disc structure and mechanical function. Delivery of therapeutic RNA using lipid nanoparticles (LNPs) is a novel strategy with the potential to arrest and reverse fibrotic tissue changes in the NP. An advantage of LNPs is their modular design, whereby their properties can be optimized to improve biodistribution and intracellular delivery for specific tissues, and non-viral nucleic acid delivery is safer than viral vector-based gene therapy. The overall goal of this proposal is to establish a safe and effective, extended-release RNA-based therapy that arrests and reverses the pro-fibrotic changes that drive progressive structural and functional failure of the disc NP during degeneration. In Aim 1 we will optimize an LNP formulation and establish a novel extended release microcarrier for delivery of therapeutic RNA to NP cells over clinically relevant time scales. Next, in Aim 2 we will undertake in vitro cell culture studies to optimize the RNA therapy to synergistically arrest the pro-fibrotic transformation of the NP via ablation of mechano-active signaling and stimulation of healthy tissue formation. Finally, in Aim 3, the safety, efficacy and cellular mechanisms of the optimized therapy will be evaluated in ex vivo organ culture and an in vivo large animal model of moderate severity disc degeneration.