Grants

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Project Summary Bile acids (BAs) have emerged as a rich and important source of immunoregulatory metabolites in the intestines. Yet current views of BAs are incomplete. Reductionist studies administering single BAs to cells or mice, while useful for informing basic BA physicochemical properties, engender ‘1 BA = 1 function’ models that have limited relevance to the vastly more complex physiology that underpins BA metabolism and signaling in vivo. Our goals are to quantify intestinal BA pools in mice, understand how and why they change during intestinal inflammation, and map their interactions with host intestinal cells and receptors. Recognizing that intestinal BA pools are formed and dynamically regulated by endocrine-like signaling connections between the liver (where BAs are made), ileum (where most BAs are absorbed) and colonic microbiota (where most BAs are metabolized), we developed an integrated methods set to interrogate the size, complexity, regulation and function of intestinal BA pools in mice. We validated these approaches in mice that lack the ileal BA reuptake transporter, Asbt/Slc10a2, and that harbor robust and predictable differences in BA metabolism. We also established new computational models, calibrated to in vivo datasets, that offer quantitative insights into the independent inputs that hepatic synthesis, ileal absorption and microbial metabolism each contribute to the establishment and maintenance of enterohepatic BA pools. New preliminary data suggest that Crohn’s disease-like ileitis, which arises spontaneously in human Crohn’s disease patients and TnfARE/+ mice, alters BA circulation and metabolism in ways that ultimately produce a smaller and more pro-inflammatory BA pool. We hypothesize that aberrant ileal BA absorption is triggered by cytokine-driven Asbt downregulation in enterocytes prior to overt histopathology and is a distinctive feature of ileitis in mice and humans Once produced, we posit the ileitis-associated BA pool propagates immune dysfunction and ileitis by disturbing the balance of pro- vs. anti-inflammatory NR ligands available to T cells. We test these hypotheses through two inter-related, but not inter-dependent, aims. We expect these studies will have broad and lasting impacts in the field, both by generating fundamental new insights into the regulation of BA homeostasis, and by yielding actionable new paradigms in the understanding and treatment of human Crohn’s disease.

Up to $796K

2030-04-30

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Bilingual Children with DLD: A Neurodevelopmental Perspective

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

Contact PD/PI: Kovelman, Ioulia PROJECT SUMMARY/ABSTRACT At the onset of English-dominant schooling, bilinguals with developmental language disorders (DLD) generally experience a progressive decline in home language use. Yet, theories posit that a bilingual’s two languages interact in ways that enhance children’s developing language faculty (Hernandez, 2018). To advance new perspectives on neurodevelopmental disorders of cognitive function and inform clinical approaches for linguistically-diverse learners, we seek to understand language development in bilingual children with DLD. Our objective is to uncover how bilingualism impacts language development in children with DLD. Wang et al. (2021) bridge the Interactive Specialization (Johnson, 2011) and Dual Stream (Poeppel, 2012) frameworks to conceptualize language development as an interaction between neurocognitive systems competing for language subfunctions. To examine the effects of bilingualism on DLD, we advance this perspective by linking it to the view that bilingual experiences influence extrinsic brain-behavior and intrinsic neural interactions (Hernandez, 2018). We thus hypothesize that added interactivity and competition of two languages will be positively associated with cortical specialization for language function in bilinguals with DLD. To test this hypothesis, we focus on syntactic and semantic competences disproportionately affected in DLD. We use behavioral and functional Near Infrared Spectroscopy (fNIRS) neuroimaging measures, testing Spanish-English bilinguals ages 7-9 (N=400, 60 with DLD), in two languages. Sentence judgment and narrative comprehension tasks are used to uncover cortical specificity along the dorsal and ventral language neurocircuits. Aim 1 is to determine language-specific effects of bilingualism on the finetuning of cortical specialization for language function in DLD. Aim 2 is to uncover the global-system effects of bilingualism on cortical specialization for language in DLD. To achieve these aims, we examine the relation between children’s syntactic and semantic competences in each language, the relative balance in dual language experiences, and their interaction with children’s emerging neural architecture for language. This principled approach will provide an empirical basis to (1) uncover mechanisms that support the advancement of English proficiency in bilinguals with DLD; (2) advance theories of DLD through neuro-cognitive evidence on language competences most affected in DLD; (3) inform intervention by illuminating individual differences in the relations between language experiences, proficiency, and brain development. This evidence will reveal mechanisms by which language experiences and proficiency interact with DLD, providing theoretically rich and clinically significant information. Project Summary/Abstract Page 6

Up to $539K

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Biloxi National Cemetery Expansion and FCA Deficiencies

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

Biloxi National Cemetery Expansion and FCA Deficiencies

general

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Bimodal conformations of Smc5/6 regulate molecular activities and anti-genotoxic functions

NIEHS - National Institute of Environmental Health Sciences

PROJECT SUMMARY/ABSTRACT Humans are constantly exposed to environmental genotoxins, inducing DNA lesions that lead to mutations and diseases such as cancer and developmental defects. To preserve genome integrity, cells have evolved a highly conserved network of pathways to repair DNA lesions and manage DNA replication. In eukaryotes, a key member of this network is the conserved Smc5/6 complex, which has direct roles in DNA repair and replication. Smc5/6’s functions are critical, as its dysfunction sensitizes cells to many genotoxins and devastating genome instability syndromes in humans. Despite its importance in genome maintenance, how Smc5/6 performs its anti- genotoxic functions is poorly understood. Uncovering the core principles by which Smc5/6 modulates its genomic functions is critical in understanding how cells respond to environmental genotoxins and in advancing new avenues for treating diseases. Our structural data have revealed two competing conformations of budding yeast Smc5/6 that are proposed to regulate its key activities of DNA binding and ATP hydrolysis. These conformations, termed the Nse4-neck and Nse6-neck states, are required to protect against genotoxic stress. Further, genetic tests have revealed that each conformational state is required for specific Smc5/6-mediated functions in DNA replication termination and repair intermediate removal. Thus, we hypothesize that the two Smc5/6 conformational states regulate the complex’s key biochemical activities to enable distinct genome protection roles. To test this hypothesis, this project will investigate Smc5/6’s functional mechanisms using a combination of in vitro and in vivo approaches in budding yeast. Aim 1’s experiments will examine how the two distinct conformational states of Smc5/6 regulate its biochemical activities of ATP hydrolysis and DNA binding. Aim 2 will build on preliminary genetic findings suggesting that the Nse4-neck state of Smc5/6 is recruited to stalled replication forks at rDNA sites to aid replication termination. We will test how the Smc5/6 Nse4-neck state impacts replication termination and Smc5/6 chromatin localization through genomic approaches. In Aim 3, we will expand on previous work suggesting the Nse6-neck state of Smc5/6 modulates recombinational repair factors like Sgs1 to aid in removing DNA repair intermediates. As such, we will test how perturbing the Nse6-neck state in cells affects Smc5/6-mediated repair intermediate removal and Sgs1 modulation. These Aims will reveal the mechanisms by which Smc5/6 drives its genome integrity functions to provide widespread genotoxin resistance. As Smc5/6 mutations cause genotoxin sensitivity and diseases such as genome instability syndromes, this research will guide the study of human Smc5/6 into its disease-causing mechanisms. This research plan will provide the F31 candidate strong training in the genome integrity field under the guidance of the sponsor Dr. Xiaolan Zhao, an expert in Smc5/6 biology and genome maintenance processes. Further, the candidate’s network of committed mentors and collaborators will drive their progress in mastering multidisciplinary research approaches, developing mentoring skills, and cultivating strong communication skills.

Up to $50K

2029-05-31

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Binghamton Community Power Phase II: Clean Energy Empowerment for Environmental Justice Neighborhoods

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.

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Binghamton Community Power Phase II: Clean Energy Empowerment for Environmental Justice Neighborhoods

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.

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

Binghamton Community Power Phase II: Clean Energy Empowerment for Environmental Justice Neighborhoods

BINGHAMTON REGIONAL SUSTAINABILITY

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

Binghamton Community Power Phase II: Clean Energy Empowerment for Environmental Justice Neighborhoods

BINGHAMTON REGIONAL SUSTAINABILITY

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

Binghamton Community Power: Promoting Environmental Protection, Fiscal Stability, and Public Health in Environmental Justice Neighborhoods

Binghamton Regional Sustainability Coalition

To measure the rate of energy poverty, its impact on residents, and the barriers to adopting energy conservation practices.

Up to $97K

environmentHealthjustice

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Binghamton Community Power: Promoting Environmental Protection, Fiscal Stability, and Public Health in Environmental Justice Neighborhoods

Binghamton Regional Sustainability Coalition

To measure the rate of energy poverty, its impact on residents, and the barriers to adopting energy conservation practices.

Up to $97K

environmentHealthjustice

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Bio-based additives as alternatives to unlock and increase recyclability and/or biodegradability

European Commission - HORIZON

Bio-based additives as alternatives to unlock and increase recyclability and/or biodegradability. Call: HORIZON-JU-CBE-2026. Programme: HORIZON. Keywords: Applied and industrial chemistry, Bioprocessing technologies (industrial processes relying on biological agents to drive the process) biocatalysis, fermentation, Industrial biotechnology, Polymers and plastics. Open call from the EU Funding & Tenders Portal.

2026-09-22

technology

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Bio-based chemicals and/or materials from woody residues

European Commission - HORIZON

Bio-based chemicals and/or materials from woody residues. Call: HORIZON-JU-CBE-2026. Programme: HORIZON. Keywords: Forest ecosystem services, Forestry, Forestry, biomass production (e.g. for biofuels), Materials engineering. Open call from the EU Funding & Tenders Portal.

2026-09-22

research

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Bio-based innovation in society: supporting the sustainable way of living

European Commission - HORIZON

Bio-based innovation in society: supporting the sustainable way of living. Call: Call 01 - single stage (2026). Programme: HORIZON. Keywords: Bio-based products (products that are manufactured using biological material as feedstock) bio-based materials, bio-based plastics, biofuels, bio-based and bio-derived bulk and fine chemicals, bio-based and bio-derived novel materials, Biochemical research methods, Biochemistry and molecular biology, Biodiversity conservation, Bioprocessing technologies (industrial processes relying on biological agents to drive the process) biocatalysis, fermentation, Environmental biotechnology, Environmental engineering, Industrial biotechnology, Materials engineering, Social innovation, Social sciences, interdisciplinary, Sociology. Open call from the EU Funding & Tenders Portal.

environmenttechnologysocial_justice+2

2026-09-17

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Bioactive Injectable Implants for Functional Intervertebral Disc Regeneration

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.

2029-12-31

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Biobehavioral Signatures of Repetitive Head Impacts at the Intersection of Aging and Alzheimer's Disease

NIA - National Institute on Aging

ABSTRACT Millions of older adults are at increased dementia risk because of prior exposure to repetitive head impacts (RHI), such as those from contact sports, military service, intimate partner violence, and other sources. Investigating common, globally relevant, environmental dementia risk factors like RHI is a public health imperative. We lack a fundamental understanding of how RHI leads to cognitive decline, including the distinct biological pathways and brain regions that are disrupted. Further, the intersection of prior RHI with common diseases of aging, such as Alzheimer’s disease (AD), cannot be ignored given the potential for a synergistic negative impact on brain health. Progress towards accurately identifying (diagnosis) and effectively treating RHI-related brain changes depends on defining key molecular and brain structure correlates of RHI. Our multi-site, multidisciplinary team is uniquely positioned to address these critical gaps and make substantial strides towards precision care for aging adults with prior RHI. This proposal builds directly on our strong portfolio of published research and compelling preliminary data pointing us towards the importance of 1) altered inflammation and immune-signaling pathways and 2) vulnerability of limbic system structures seen several years downstream of RHI, distinct from the effects of AD, and potentially explaining later-onset of RHI-related cognitive decline. We aim to accelerate our recent progress through a longitudinal study of fluid biomarkers, neuroimaging, and cognition in aging adults with and without RHI to parse RHI effects on brain aging (i.e., RHI “signatures”). In this R01 from an Early-Stage Investigator (ESI), we will investigate intersections of aging, RHI, and AD using the collective infrastructure of 3 ADRCs (1Florida, Boston University, University of California-San Francisco). We will identify data-driven molecular (plasma proteomics; Aim 1) and brain structure (multimodal MRI; Aim 2) signatures of RHI and map onto cognitive trajectories (Aim 3). The primary cohort will be strategically sampled to study 400 older adults with representation across the RHI, AD pathology, and cognitive continuums. Robust validation of our findings will be performed two ways: 1) internal validation – longitudinal subset within the primary study cohort, 2) external validation – independent sample enriched for RHI across the cognitive and AD pathology continuum (DIAGNOSE-CTE II). Our methods are conceptually and technically innovative: multi-site gold standard head trauma measurement integrated with deep clinical and biological phenotyping, Subtype and Stage Inference modeling (SuStaIn), large-scale proteomics and bioinformatics from ~11,000 proteins (SomaScan®), leading- edge brain MRI (hippocampal subfield analysis, free water diffusion), and modeling the full continuum of RHI exposure. Executing this ESI-led project will provide foundational knowledge of the relationships between RHI, AD, and aging. Identifying RHI-related molecular targets, brain atrophy and white matter injury patterns, and cognitive correlates are essential steps for understanding mechanisms, accurately modeling disease progression, and developing interventions for millions of at-risk older adults with prior RHI.

Up to $440K

2028-05-31

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Biobehavioral Synchrony and Hormonal Correlates of Parenting from Pregnancy to Toddlerhood: A Longitudinal, Multi-Method Study of First-Time Fathers and Mothers

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

PROJECT SUMMARY Psychological, hormonal, and neural adaptations during the transition to parenthood shape early caregiving behaviors and may set the course for children’s long-term socioemotional and physical health. A growing body of research highlights biobehavioral synchrony, the coordination of behavioral and neural responses between caregivers, as a key mechanism supporting early family functioning. However, little is known regarding how biobehavioral synchrony between parents emerges during pregnancy, how it evolves through infancy and toddlerhood, and how it may contribute to child outcomes. This K99/R00 project addresses these gaps by investigating father–mother biobehavioral synchrony in the prenatal period, its role in shaping early caregiving, and its subsequent associations with postnatal triadic biobehavioral synchrony and child health-related outcomes. Using a novel, multi-method approach, the project will integrate functional near-infrared spectroscopy (fNIRS) and microanalytic coding to assess neural and behavioral synchrony. In addition, salivary hormone assays (cortisol reactivity and testosterone) during structured family interactions will measure hormonal changes. During the proposed K99 training phase, a small pilot sample of ~10 expectant couples will complete prenatal neural, hormonal, and behavioral assessments and be followed postnatally at 8 months as triads, providing an opportunity to refine the multi-method protocol, assess feasibility, and gain hands-on training in all study procedures. Building on this foundation, the R00 phase will scale the study to ~80 families assessed at four time points: prenatally, and at 8, 20, and 30 months postpartum. The project is guided by three aims: (1) pilot assessments of prenatal father–mother neural and behavioral synchrony and hormonal reactivity; (2) test longitudinal associations between prenatal dyadic synchrony and postnatal triadic synchrony, caregiving behaviors, and parent–child interactions; and (3) examine how pre- and postnatal synchrony and hormonal reactivity may shape children’s socioemotional functioning and health-related behaviors. By incorporating both parents and focusing on the prenatal emergence of synchrony, this proposal advances current models of family systems and child health. It also supports NICHD’s mission by identifying modifiable, biologically embedded processes that promote healthy family relationships and child outcomes. I will receive interdisciplinary training in fNIRS (Dr. Koraly Pérez-Edgar), hormonal analysis (Dr. Darby Saxbe), microanalytic behavioral coding of interparental and parent–child interactions (Dr. Natasha Cabrera), and intensive longitudinal modeling (Dr. Zachary Fisher). My training plan includes graduate-level coursework, advanced statistics workshops, a salivary data collection and assay bootcamp, and hands-on experience conducting neural, hormonal, and behavioral data collection. Together, this training—supported by an outstanding team of mentors—will prepare me to launch an independent, translational research program focused on biobehavioral dynamics in early family development and child health.

Up to $120K

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BioBlitz Data Analysis and Great Basin Landscape Report

National Park Service

NatureServe will assist the NPS to review, organize, and assess the results of these BioBlitzes for their scientific value and other potential benefits to park management.

rolling

natural resources

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BioBlitz Interns

National Park Service

In celebration of the National Park Service (NPS) Centennial, the tenth in a series of annual BioBlitzes, co-hosted by NPS and the National Geographic Society (NGS), will be centered in national park sites in and around Washington, D. C. BioBlitz is a two day event focusing around a 24 hour inventory period in which teams of scientists, teachers, children, and other community members work together to identify as many species as possible. The event also includes a Biodiversity Festival featuring hands-on activities, speakers, and exhibits. The 2016 BioBlitz and Biodiversity Festival will take place on Friday May 20 and Saturday May 21. Simultaneously, BioBlitzes will occur at national park sites across the country.

$1 – $78K

rolling

Education

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Biocatalytic Generation and Bioactivity Investigation of Naphthylisoquinoline Alkaloids

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT Global cases of malaria reached 263 million people in 2023, an eight percent increase from 2022, and the disease has led to estimated annual death tolls of half a million people. Over the next two decades, the global health burden of neglected tropical diseases (NTDs) and malaria is projected to increase further based on an analysis of data from the 2021 Global Burdens of Disease Study. The emergence of Plasmodium strains that are resistant to the current suite of registered antimalarial drugs creates significant challenges in combatting the disease and necessitates the development of novel small molecule antimalarial therapies. Looking to nature, root extracts from the Southeast Asian woody liana Ancistrocladus tectorius have historically been used to treat malaria. The plant species A. tectorius showcases a wide breadth of biaryl naphthylisoquinoline alkaloid (NIQ) metabolites. These NIQs have garnered interest due to their complex architectures and pharmacological properties against tropical diseases. Although the bioactivity of some NIQs has been characterized, our inability to readily obtain many of the molecules in this class of natural products hinders broader characterization. Thus, the biaryl NIQs are fascinating complex targets for selective synthesis with potential utility in combatting malaria and other NTDs. Strategies to access these molecules can require pre-functionalization of the coupling partners, forcing conditions, and can suffer from limited yields and selectivity challenges. In contrast, Nature has evolved versatile heme-dependent cytochrome P450 monooxygenases (P450s) capable of a wide breadth of oxidation chemistry. A biocatalytic oxidative coupling approach offers an efficient alternative strategy for catalyst-controlled selective biaryl C–C bond formation under mild conditions with molecular oxygen as the stoichiometric oxidant. Herein, I propose that profiling of a wild-type P450 library coupled with enzyme engineering to improve both enzyme reactivity and selectivity will enable the chemoenzymatic synthesis of naphthylisoquinoline alkaloids (NIQs) and their subsequent bioactivity characterization. A biocatalyst will be optimized via directed enzyme evolution for the target-oriented synthesis of the antimalarial NIQ ancistrotanzanine C. Further P450 library reactivity profiling and enzyme engineering will generate a suite of biocatalysts a broader scope of NIQs with varying site-selectivity and coupling partners. Synthesized NIQs will be characterized for potential inhibitory activity against a cysteine protease target implicated in malaria and crystal formation that protects Plasmodium from a toxic environment during hemolysis. The proposed work will accelerate the development of novel small molecule alternatives for treating malaria and other neglected tropical diseases.

Up to $44K

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Biodiversity on a Changing Planet

U.S. National Science Foundation

The biodiversity found in nature is essential for healthy ecosystems and human well-being. However, the disruption and decline of Earth s biodiversity is currently occurring at an unprecedented rate. The resulting shifts in biodiversity dynamics including changes in the scope and structure of biodiversity are increasingly significant but not well understood. Shifting biodiversity dynamics (i.e., shifts in scope, structure, and interactions of biodiversity) in turn influence functional biodiversity, which includes the roles of traits, organisms, species, communities, and ecosystem processes in natural systems. Changes in biodiversity dynamics and functional biodiversity are components of future planetary resilience under environmental change, including climate change. The connection between functional biodiversity and biodiversity dynamics on a changing planet is the main focus of the Biodiversity on a Changing Planet (BoCP) program. The program encourages proposals that integrate ecological and evolutionary approaches in the context of the continual gain, loss, and reorganization of biodiversity on a changing planet. To advance a comprehensive understanding of functional biodiversity requires a highly integrative approach including consideration of spatial and temporal dimensions from the organismal to the ecosystem level, and from recent to deep timescales. The BoCP program is a cross-directorate and international program led by NSF that invites submission of interdisciplinary proposals addressing grand challenges in biodiversity science within the context of unprecedented environmental change, including climate change. Successful BoCP proposals will test novel hypotheses about functional biodiversity and its connections to shifting biodiversity on a changing planet, with respect to both how environmental change affects taxonomic and functional biodiversity, as well as how the resulting functional biodiversity across lineages feeds back on the environment. Proposals that seek to improve predictive capability about functional biodiversity across temporaland spatial scales by considering the linkages between past, present, and future biological, climatic, and geological processes are also encouraged. While this focus complements several core programs at NSF, it differs by requiring an integrative approach to understanding functional biodiversity as it relates to shifting biodiversity under changing environmental conditions. The program supports both US-only collaborative proposals and proposals with international partnerships with the National Natural Science Foundation of China (NSFC), the S o Paulo Research Foundation (FAPESP) of Brazil, and the National Research Foundation (NRF) of South Africa. International collaborative proposals are to be submitted jointly, with the US PIs submitting to NSF and the collaborating Chinese, Brazilian, or South African PIs submitting to their appropriate national funding agencies. These agreements do not preclude other international collaborations (see solicitation for additional details).

rolling

sciencetechnology

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Bioeconomy policy support hub for Member States, regions and sectors

European Commission - HORIZON

Bioeconomy policy support hub for Member States, regions and sectors. Call: Call 01 - single stage (2026). Programme: HORIZON. Keywords: Bioeconomy, EU research policy /Research policies in the EU, Industrial policy, Innovation policy, Public administration. Open call from the EU Funding & Tenders Portal.

Business Developmentresearch

2026-09-17

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Bioengineered Models of Intramural Uterine Fibroids: A Dual-Platform Approach to Study Molecular Transport Barriers and Biochemical Interactions

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

PROJECT SUMMARY Uterine fibroids, also known as leiomyoma, affect 70-80% of women in the United States of reproductive age and carry significant health and economic burdens. Fibroids are benign fibroproliferative tumors characterized by excessive extracellular matrix (ECM) deposition and remodeling that alters the biophysical and biochemical microenvironment, cell interactions, and access to signaling molecules (i.e., hormones, growth factors) and treatments. Yet, knowledge gaps remain regarding how these factors influence fibroid behavior, and there are limited preclinical in vitro models for uterine fibroids that recapitulate 3D tissue architecture, cell interactions, and relevant microenvironmental features. There is a significant need for improved in vitro models for uterine fibroids with pathophysiologically relevant cell interactions, tunable biophysical properties, and biochemical signaling to effectively study fibroid biology and advance therapeutic development. The proposal objective is to leverage two novel in vitro models of uterine fibroids—one with tunable transport properties and one representing intramural uterine fibroids (fibroids surrounded by myometrium)—to study how altered signaling from sex hormones (estrogen, progesterone), obesity, and therapeutics affect fibroid growth. This work supports the long-term goal of developing predictive in vitro models of uterine fibroids—across all subtypes—to study fibroid initiation, growth, persistence, and recurrence. Aims will test the central hypothesis that fibrotic biophysical properties within the fibroid microenvironment and fibroid-myometrium interactions contribute to fibroid growth and treatment response by reducing molecular transport and modulating the activity of sex hormones, obesity-related factors, and therapeutics. The objective will be accomplished by two Specific Aims: Aim 1 – Characterize fibroid cell responses to molecular transport barriers using a novel tunable collagen-alginate interpenetrating polymer network (IPN) model and Aim 2 – Establish a self- assembled myometrial tissue ring model with embedded fibroid spheroids for evaluating fibroid cell responses to hormones, obesity, and treatment. In Aim 1, we will change fabrication parameters for type I collagen-alginate IPN hydrogels to tune stiffness to that of myometrium and fibroid tissue and reduce molecular transport. A tissue model with a fibroid-tissue sphere embedded within an IPN hydrogel will then be used to evaluate how reduced molecular transport of bioactive molecules of varying size influences functional outcomes, including proliferation, metabolic, activity, and apoptosis, using high throughput and content multiplexed analysis. In Aim 2, self-assembled uterine smooth muscle tissue rings with embedded uterine fibroid spheroids (fibroid cells, fibroblasts) will undergo separate exposures: 1) estrogen and progesterone hormone at concentrations representing a normal menstrual cycle (luteal and follicular phase) and pregnancy (three trimesters); 2) conditioned medium from lean and obese adipocytes; 3) clinically relevant dose of Leuprolide—a gonadotropin-releasing hormone agonist that suppresses estrogen and progesterone production. Models will be evaluated on fibroid growth and related processes, primarily proliferation, apoptosis, and ECM production. Collectively, these studies will provide new insights into how the fibroid microenvironment influences fibroid growth and treatment response, while establishing innovative in vitro models that serve as platforms for future mechanistic and therapeutic investigation.

Up to $555K

2029-05-31

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Bioengineered Networking Microbes for Targeted Colon Cancer Therapy

NCI - National Cancer Institute

Project Summary Colon cancer remains a critical global health challenge, intensified by the rising incidence of early-onset disease and the persistence of immunologically cold and metastatic tumors that evade conventional therapies. To address these unmet needs, this project develops bioengineered networking microbes, a coordinated system of genetically modified bacteria designed to selectively target tumors and reprogram the host immune environment. We have developed genetically modified Salmonella (GMS) engineered to deliver TRAIL and capable of homing to tumor sites, colonizing the tumor microenvironment, and initiating localized inflammatory responses that increase tumor immunogenicity. In multiple preclinical mouse models, TRAIL-expressing GMS induce potent tumor cell apoptosis, amplify immune activation through the release of tumor-associated antigens, inhibit tumor growth, prolong survival, and reduce metastatic spread. Complementing this oncolytic platform, we also engineer beneficial gut bacteria to restore microbial balance, reduce inflammation, and modulate metabolites implicated in colon cancer progression. By integrating tumor-targeting bacteria with microbiome-restorative strains, we propose a synergistic therapeutic approach in which engineered microbes communicate and cooperate to enhance tumor targeting, strengthen anti-tumor immunity, and improve overall treatment efficacy. Animal models are essential for proposed research to evaluate the safety, biodistribution, and therapeutic efficacy of the engineered microbial consortium within the complex tumor and immune microenvironment. They also enable investigation of host-microbiome-tumor interactions and cooperative microbial behaviors that cannot be adequately replicated in vitro. If successful, this project will establish a transformative paradigm in colon cancer therapy-leveraging networked, multifunctional microbes as both precise local activators of anti-tumor immunity and systemic modulators of gut health to achieve durable and broadly applicable therapeutic responses.

Up to $404K

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Bioengineering a human pluripotent stem cell system for studying inner ear development

NIDCD - National Institute on Deafness and Other Communication Disorders

Human pluripotent stem cells (hPSCs) have been demonstrated to be powerful tools to study human biology and diseases, especially for which human tissue is difficult to access to and biopsy is challenged to obtain. Inner ear is one of organs that is nearly impossible to access without causing damages. Moreover, it is rare to obtain human inner ear biopsy. However, inner ear disorders, including hearing loss and vestibular dysfunction, are one of the most common sensory disorders. Although animal studies have advanced our understanding in hair cells, the underlying cellular processes may differ from those of human. A human cell-based model is therefore needed to progress our understanding of inner ear and the development of therapeutic strategies. Recently, stem cell-derived three-dimensional (3D) inner ear organoids have been reported to mimic certain aspects of inner ear development and disease pathologies in vivo. Despite this potential, there are limitations in the 3D inner ear organoid system to faithfully recapitulate some developmental processes, e.g., morphogen gradients that are critical for proper patterning. Therefore, we first propose to develop an innovative microphysiological system featuring a microfluidic chip that can precisely establish desired morphogen concentration gradients to which large size, 3D organoids are subjected on-chip (Aim 1). We will mediate BMP, WNT, and SHH signaling pathways to model dorso-ventral patterning in otic vesicles as a proof of concept. Results will assist us to understand how to induce the proper dorso-ventral patterning such that a similar strategy can be applied to effectively induce ventralization in the hPSC-based inner ear organoid system. As many inner ear disorders stem from malfunction of or damages in hair cells, we then propose to understand regulatory processes for the hair cell formation with special focus on epigenetic regulatory mechanisms, which is poorly understood, using the hiPSC-derived 3D inner ear organoid system (Aim 2). We propose to generate comprehensive epigenetic and transcriptomic regulatory networks for nature occurring hair cell differentiation and post-damage-induced hair cell regeneration using single cell (sc) muti-‘Omic approaches. Furthermore, we will validate the findings from sc multi-‘Omic approaches by testing the effects of the identified regulatory enhancer regions and genes in hair cell regeneration using CRISPR/dCas9-based assays (Aim 3). This will allow us to mimic epigenetic regulation of gene expression during hair cell formation. This project is not only improving the technology for the organoid system, but also providing the first step towards systematically advancing our knowledge of the role of epigenetics in human hair cell formation and, ultimately, developing therapeutic strategies for damaged hair cells.

Up to $485K

2031-04-30