The Advancing Clinical Translational science for Rehabilitation (ACT4Rehab) research career development program addresses critical gaps in the current NIH portfolio of rehabilitation research. Advancements in the medical management of life-threatening diseases and traumatic injuries are increasing survival and longevity while also increasing the prevalence of chronic illness and physical disabilities. While great rehabilitation research is occurring, rehabilitation translational science is needed to ensure that our health systems and communities deliver the right care to the people who can benefit most from rehabilitation at the right time. ACT4Rehab will create a mentoring network to support a national cohort of rehabilitation clinician scholars capable of becoming independent scientists who lead research programs that restore, increase, and maximize capabilities to positively impact the lives of people with disabilities. ACT4Rehab will conduct widespread outreach to academic and clinical research programs to recruit and select rehabilitation clinician scholars in occupational therapy, physical therapy, and rehabilitation medicine who have an identified scientific domain with high translational potential for clinical implementation. We will train the scholars and their mentors to augment their clinical research expertise with skills in novel intervention research frameworks, study design, and methods; engagement and collaboration practices with shareholders (i.e., the persons for whom the implementation is designed, their families, healthcare providers, health care systems, payors and industry partners); and implementation design and evaluation frameworks, methods, and tools. This training will ensure that ACT4Rehab scholars will be able to advance and accelerate rehabilitation translational science by “designing for implementation” at all stages of intervention development. We will sustain the impact of ACT4Rehab by training mentors and scholars in mentoring best practices to ensure that ACT4Rehab training in clinical research and clinical implementation is available to successive generations of rehabilitation translational scientists. We will further sustain the impact of ACT4Rehab by expanding existing clinical translational science infrastructure to include rehabilitation specific need via establishment of a national ACT4Rehab network with accompanying web-based resources. ACT4Rehab’s impact will be measured by the degree to which we advance and accelerate high quality clinical translational science in rehabilitation to the benefit of society, as measured using the Translational Science Benefit Model.

Up to $931K

2031-03-31

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Actin cytoskeleton organization and function in health and disease

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NIGMS - National Institute of General Medical Sciences

Project Summary/Abstract The overarching goal of this proposal is to explore novel aspects of the actin cytoskeleton organization and function in health and disease. The remarkable functional versatility of the actin cytoskeleton stems from its ability to assemble into a variety of diverse structures – branched networks/meshes and aligned bundles. This architectural complexity is orchestrated by actin-binding proteins, whose activity is delicately regulated in response to internal and external signals. Human plastins are versatile actin-binding proteins that organize actin filaments into higher-order assemblies: bundles and networks. Plastins are involved in cytokinesis, migration, and stabilization of membrane protrusions, but also in the pathogenesis of the following diseases: carcinogenesis, neurodegeneration, and hereditary and infectious diseases. Despite the importance and long- lasting interest of the research community in these proteins, understanding of their interaction with actin and their regulation is superficial. Our first research direction is to contribute to human health and well-being by advancing the understanding of the actin cytoskeleton organization by actin-bundling proteins plastins and their contribution to pathologies (e.g., congenital diseases and metastatic cancers) at the molecular and cellular levels. Playing numerous vital roles in human defense mechanisms, the actin cytoskeleton is a common target for numerous bacterial pathogens, which developed various elegant and sophisticated ways to disrupt and usurp it by producing actin-targeting effectors. By hijacking the actin cytoskeleton, pathogenic toxins disturb cell morphology, cell motility, phagocytosis, epithelial permeability, and antigen presentation. Being constantly adjusted to the host cytoskeleton by co-evolution, they recognize weaknesses in the host defense and represent powerful tools that foster the understanding of the cytoskeleton on molecular and cellular levels. The urge for a thorough understanding of bacterial pathogenicity is further necessitated by the dissemination of multidrug- resistant pathogens that undermine the efficiency of antibiotics. The second research direction of this proposal is to decipher the in-depth molecular and cellular mechanisms of bacterial effectors targeting the actin cytoskeleton to i) enable alternative ways of targeting pathogens and ii) get a deeper understanding of the actin cytoskeleton per se. The current proposal is directly relevant to the NIH mission as it focuses on three families of bacterial effectors, all produced by human pathogens: Vibrio cholerae and Vibrio parahaemolyticus VopF/VopL (1) and VopM/VopV (2), and Legionella pneumophila MavH, RavH, and VipA (3). Furthermore, the proposal is of interest for a general understanding of human physiology as each of the above toxins reveals novel properties of the actin cytoskeleton. Finally, the understanding of the molecular and cellular mechanisms governing the function of actin-bundling proteins plastins contributes to explaining the pathology of plastin-related human diseases.

Up to $442K

2031-04-30

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Acting under uncertainty: neural dynamics underlying self-generated action decisions

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NINDS - National Institute of Neurological Disorders and Stroke

Project summary/abstract Making decisions under uncertainty is essential for learning and survival, yet the neural mechanisms that support such decisions remain poorly understood. This proposal investigates how the brain determines when and where to act in the absence of external cues, with a focus on the neural dynamics of cortical, thalamic, striatal, and cerebellar circuits. Aim 1 (K99 phase) will identify the neural dynamics that distinguish self-generated from sensory-driven temporal decisions (“when to act”), using an innovative behavioral paradigm, simultaneous multi-area neural recordings and computational methods. Aim 2 (K99/R00 phase) will establish causal principles by testing how specific brain circuits influence the timing of self-generated decisions, leveraging real-time, closed-loop optogenetic perturbations. Aim 3 (R00 phase) will extend this framework to self-generated spatial decisions (“where to act”), using a modified two-alternative choice paradigm to determine how the brain resolves ambiguity when external instructions are incomplete or absent. The candidate’s long-term goal is to lead an independent research program in cognitive systems neuroscience that integrates circuit-level mechanisms with exploratory behavior and decision-making. The mentored K99 phase will provide advanced training in computational methods and closed-loop optogenetics. Northwestern University offers an outstanding environment for this training, with world-class facilities, interdisciplinary expertise, and a strong community in systems, computational, and behavioral neuroscience. The R00 phase will allow the candidate to establish an independent research laboratory with a program that remains cohesive with prior work while significantly expanding in scope. This research will advance fundamental knowledge of voluntary action and may inform therapeutic strategies for neurological and psychiatric conditions that affect decision- making, including Parkinson’s disease, obsessive-compulsive disorder, and abulia.

Up to $117K

2028-07-31

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Action Likelihood to Evaluate Weakness, Abnormal Motor Synergies, and Spasticity in Stroke Survivors

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

PROJECT SUMMARY/ABSTRACT Upper limb motor impairments such as weakness, abnormal synergies and spasticity affect over two-thirds of stroke survivors, with one stroke occurring every 40 seconds in the United States. These deficits often persist long after the acute event, severely limiting individuals’ ability to perform daily activities. To maximize recovery with personalized rehabilitation, clinicians rely on manual muscle testing and comprehensive clinical assessments. However, these evaluations are time-consuming and subjective. Attempts to streamline evaluations using electromyography or marker-based motion tracking are impractical for routine clinical use. There is a critical need for a scalable, objective tool that leverages markerless upper limb movement data to rapidly identify deficits and predict clinical scores so therapists can devote more time in therapy. Our long-term goal is to quantify weakness, abnormal synergies, and spasticity from just two minutes of free exploration movement. Previously, we have shown that the probability distributions of wrist position in a free exploration task where participants move based on their own preferences can uncover flexion synergy patterns in over half of stroke survivors and identify regions of weakness in all stroke survivors. Based on this encouraging preliminary evidence, our central hypothesis is that comparing a stroke survivor’s portfolio of kinematic probability distributions, termed action likelihoods, to those of neurotypical participants will reveal individualized signatures of motor impairment. Our rationale is that each impairment alters the preferred movement patterns within a person’s available range of motion in distinct, quantifiable ways. In Aim 1, we compare action likelihoods of stroke survivors with weakness to those of neurotypical participants and to predictions from a neuromusculoskeletal model of weakness. In Aim 2, we compare action likelihoods of individuals with abnormal synergies to those of neurotypical participants and to predictions from model of joint coupling. In Aim 3, we examine spasticity during volitional movement by comparing high-frequency kinematic features in stroke survivors to those of neurotypical participants and to those generated by a computational model of spasticity. The expected outcome is a data-driven tool based on action likelihoods that can quantify upper limb impairments during free exploration and offer insight into underlying mechanisms of motor deficits. This work moves beyond predefined task performances and captures real-world variability and movement limitations. It also establishes a novel framework for precision rehabilitation while generating a curated upper extremity movement data repository to support future research. Alongside the research project, the individualized training plan developed by the sponsor (James L. Patton, PhD, University of Illinois Chicago) and the co-sponsor (R. James Cotton, MD, PhD, Northwestern University) will support the principal investigator in gaining skills necessary to become an impactful physician-scientist.

Up to $55K

2030-07-14

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Action Strategy to Engage Youth in River Recreation and Conservation

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National Park Service

Activities supported under this agreement include conducting coordinated programs for getting young people onto their urban waterways in key cities, providing opportunities to learn outdoor and environmental skills, and providing a continuum of experiences through access to additional opportunities for recreation, career information, and skill development.

$1 – $52K

rolling

Education

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Activate Arts! Beacon Hill

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Community Dance Program

The Community Dance group will be hosting various " Fair Days" at the Centilia Cultural Center located at El Centro de la Raza 2524 16th Ave South. The Fair days will happen August 9 and September 13. The purpose of this project is to celebrate the rich diversity of the Beacon Hill neighborhood by highlighting various cultural activities and dance that reflect ethnic groups such as Latino, Asian, East African etc. The event is free and open to the public.

Up to $15K

Rolling

arts

Free to search & build · $99 one-time to unlock the application pack · No subscription

Activation of the NLRP3 Inflammasome by Dopamine Is Regulated by Dual GSDMD and GSDMB Cleavage Pathways Associated with Mitochondrial Dysregulation

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NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ABSTRACT Inflammasomes are innate immune signaling hubs that coordinate inflammatory cytokine release and pyroptotic cell death. Aberrant inflammasome activity is implicated in a broad spectrum of chronic inflammatory conditions, yet the pathways by which different physiological signals regulate inflammasome responses remain insufficiently defined. Our recent findings reveal that the dopamine (DA), classically studied as a neurotransmitter, directly primes the activation of a novel NLRP3 inflammasome activation pathway in human monocyte-derived macrophages (hMDMs). In the presence of an inflammasome activation trigger (BzATP), DA induces parallel cleavage of Gasdermin D (GSDMD) and Gasdermin B (GSDMB). This dual gasdermin response uniquely induced by DA – it was not recapitulated by any pathogen-recognition receptor (PRR) agonist tested. Notably, while GSDMD is processed through caspase-mediated activity, the GSDMB cleavage pathway mediated by DA depends on granzyme-B activity, suggesting a novel, endogenous protease pathway in human macrophages. Because GSDMB is absent in rodents, this DA–GSDMB axis potentially represents a human- specific inflammatory mechanism that has not been identified in murine systems and may underlie previously described species-specific differences in dopaminergic immune responses. While the specific trigger for DA-mediated GSDMB cleavage is not clear, our data show that DA disrupts mitochondrial homeostasis and induces glycolytic shift, which has been shown to initiate inflammasome activity. Specifically, DA treatment induces excessive mitochondrial fission driven by DRP-1 phosphorylation, elevated mitochondrial superoxide (MitoSOX), and release of oxidized mitochondrial DNA (mtDNA). These alterations temporally coincide with inflammasome activation, and inhibiting these effects by blocking DRP-1 mediated fission suppresses DA-induced inflammasome assembly and cytokine maturation. This supports our premise that DA regulates NLRP3 inflammasome activation via two mechanistically distinct but parallel pathways targeting GSDMDNT and GSDMBNT, which are directly linked to mitochondrial dysregulation. To address this, Aim 1 will identify the specific proteases responsible for GSDMB and GSDMD cleavage, determine their contributions to IL-1β secretion and pyroptosis, and define the subcellular localization of the cleaved GSDM fragments. Aim 2 will define how DA disrupts mitochondrial dynamics and metabolism to promote inflammasome assembly, using complementary pharmacologic and genetic approaches, and will map these mitochondrial effects to discrete stages of inflammasome activation. Clarifying how DA engages gasdermin-dependent and mitochondrial signaling will establish a novel human-specific inflammatory pathway and reveal mechanistic links between dopaminergic signaling, mitochondrial stress, and innate immune activation in inflammatory disease and therapeutic contexts.

Up to $50K

2028-07-27

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Active Biointegrated Living Electronics (ABLE) for Synergistic Treatment of Skin Inflammation

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NIBIB - National Institute of Biomedical Imaging and Bioengineering

Project Summary Living materials—biohybrids combining both biological and synthetic components—exhibit dynamic responses to environmental stimuli and closely resemble native biological tissues, positioning them for transformative biomedical applications. This proposal introduces the second-generation Active Biointegrated Living Electronics (ABLE) system, designed specifically to manage and treat psoriasis through the integration of living materials and state-of-the-art bioelectronic technologies. The ABLE system consists of biocompatible hydrogel composites enriched with the commensal bacterium Staphylococcus epidermidis, coupled with a flexible, wireless bioelectronic device. This integrated platform continuously monitors critical skin parameters, including pH, temperature, inflammatory biomarkers, and tissue impedance, and delivers precise, adaptive electrical stimulation for effective inflammation management. In Aim 1, we will engineer and thoroughly characterize foundational living bioelectronic components by creating hydrogel matrices that mimic the extracellular matrix, supporting robust bacterial viability and metabolic function. Concurrently, we will develop flexible printed circuit boards (FPCB) equipped with energy-harvesting antennas, microcontrollers, multimodal sensors, and stimulation electrodes. These integrated systems will facilitate seamless bioelectronic interfacing, enabling real-time data acquisition and precise control of biological responses. Aim 2 focuses on systematically mapping and optimizing device parameters through detailed in vitro studies. We will elucidate how electrical modulation influences microbial physiology, including membrane potentials, ion fluxes, metabolic activities, and extracellular vesicle production. These studies will provide critical insights into microbial function and biofilm dynamics, guiding the identification of optimal electrical stimulation parameters necessary for therapeutic applications. Aim 3 will rigorously validate the therapeutic efficacy of the ABLE platform in vivo using a clinically relevant animal model of psoriasis. By combining advanced bioelectronics with commensal bacteria-based hydrogels, we will comprehensively assess therapeutic outcomes through histological analyses, cytokine profiling, transcriptomics, microbiome analysis, and detailed characterization of T-cell subsets. This multifaceted evaluation aims to establish a clear mechanistic understanding of the microbial- electrical interactions and demonstrate the potential clinical relevance of the ABLE platform. Our integrative approach not only offers fundamental insights into bioelectronic modulation of skin microbiota and immune responses but also sets the stage for groundbreaking translational applications, revolutionizing inflammation management and treatment paradigms in personalized medicine. The proposed ABLE system is poised to significantly advance healthcare innovation by enabling precise, minimally invasive, and adaptive therapeutic strategies for chronic inflammatory skin conditions.

Up to $641K

2030-06-30

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription

Activity-dependent cell survival in the adult somatosensory dorsal horn: Implications for sensorimotor behaviors during aging

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NIA - National Institute on Aging

Project Summary/Abstract The somatosensory dorsal horn comprises an array of neuronal populations that receive sensory information from the skin. In recent years, the development of transcriptomic and intersectional genetic tools has allowed the characterization of these populations in young adult animals with respect to their distinct molecular identities and functional roles in the processing and transmission of touch, pain and itch information. Preliminary data indicate that the survival of neurons in the dorsal horn of adult mice is dependent on excitatory input from touch receptors in the skin. This has implications for the processing of somatosensory information during aging, in which the transmission of touch information is impaired by demyelination and by the loss of mechanosensory end organs including Merkel cells (Feng et al., 2018). Chronic silencing Merkel cells in young adult Atoh1CreERT2; Piezo2f/f mice results in the apoptotic loss of excitatory and inhibitory dorsal horn neurons by 20-25%, with some molecularly defined populations being highly susceptible to cell death and others being resistant. A similar pattern of neuronal cell loss by apoptosis is detected in the dorsal horn of 2-year-old mice. The objective of this proposal is to characterize activity-dependent changes to the cellular composition of the spinal dorsal horn during aging and to determine the functional consequences of dorsal horn remodeling for the execution of sensorimotor behaviors as animals age. These experiments will (1) selectively perturb activity in different classes of cutaneous afferent to identify inputs that support cell survival in adult mice; (2) identify dorsal horn populations, defined by molecular profile, that are maintained by input from the periphery; (3) identify molecularly defined dorsal horn populations that are reduced in size during aging; (4) test the hypothesis that the reduction in the size of the neuronal population marked by expression of Cck and Sst that occurs following the loss of input from Merkel cells during aging impairs the execution of skilled locomotor and other sensorimotor behaviors; Cck+/Sst+ neurons are proposed to relay cutaneous tactile information to ventral horn motor circuits. Activity-dependent remodeling of the cellular landscape of the dorsal horn has broad implications for the processing of touch, pain and itch information during aging, as well as in conditions in which peripheral input is impaired, such as the peripheral neuropathies that arise from diabetes mellitus and chemotherapy treatment. This proposal will advance our understanding of how somatosensory processing changes across the lifespan and will determine the contribution of these changes to age-related sensorimotor dysfunction. Furthermore, it will likely inform therapeutic strategies for the treatment of somatosensory and sensorimotor disorders in older populations.

Up to $620K

2031-01-31

health research

Free to search & build · $99 one-time to unlock the application pack · No subscription