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A primary focus of these programs is on the use of in vitro methods and assays using lower organisms to screen thousands of chemicals for toxicity in order to identify mechanisms of compound-induced biological activity, characterize toxicity pathways, facilitate cross-species extrapolation, and provide input to models for low-dose extrapolation.  Data generated by these methods will be used to prioritize compounds for more extensive toxicological evaluation and to develop predictive models for biological response in humans. Current approaches are limited in terms of incorporating genetic variability in toxicity testing and in assessing the effects of chemicals in multiple normal tissue and cell types, relying on immortalized cell lines or primary cell lines derived from tissues. Thus, there is a need for novel, medium- to high-throughput assays (at least a 96-well format) to evaluate the effects of chemical compounds on the differentiation of pluripotent or multi-potent stem cells as well as the effects of chemical exposures on differentiated cell types representative of various in vivo tissues. Approaches can include the use of human induced pluripotent stem (iPS) cells, approved human embryonic stem (ES) cell lines, or ES or iPS cells derived from genetically characterized mouse strains. Assays should be able to measure the effects of toxicants on the differentiation process and/or on the differentiated cells themselves; cell types of high priority include but are not limited to cardiomyocytes, neural cells, hepatocytes, endothelial cells, lung (airway or alveolar) cells, and hormonally-responsive tissues such as reproductive tissues or breast epithelial cells.

In recent years, somatic cells as therapeutic agents have provided new treatment approaches for a number of pathological conditions that were deemed untreatable, or difficult to treat. Several successful cell therapies using T cells have been demonstrated for cancer and autoimmune diseases, while stem cell therapies have given relief for heart disease and stroke. Hundreds of clinical trials are ongoing to examine efficacy of cell therapies for a variety of other diseases including diabetes, Alzheimer's, Parkinson's, and Crohn's disease. Production of therapeutic cells is currently expensive and, therefore, cost prohibitive for the large number of people who might benefit from these treatments. The overarching goal of this Advanced Biomanufacturing of Therapeutic Cells (ABTC) solicitation is to catalyze well-integrated interdisciplinary research to understand, design, and control cell manufacturing systems and processes that will enable reproducible, cost-effective, and high-quality production of cells with predictable performance for the identified therapeutic function.

In recent years, somatic cells as therapeutic agents have provided new treatment approaches for a number of pathological conditions that were deemed untreatable, or difficult to treat. Several successful cell therapies using T cells have been demonstrated for cancer and autoimmune diseases, while stem cell therapies have given relief for heart disease and stroke. Hundreds of clinical trials are ongoing to examine efficacy of cell therapies for a variety of other diseases including diabetes, Alzheimer's, Parkinson's, and Crohn's disease. Production of therapeutic cells is currently expensive and, therefore, cost prohibitive for the large number of people who might benefit from these treatments. The overarching goal of this Advanced Biomanufacturing of Therapeutic Cells (ABTC) solicitation is to catalyze well-integrated interdisciplinary research to understand, design, and control cell manufacturing systems and processes that will enable reproducible, cost-effective, and high-quality production of cells with predictable performance for the identified therapeutic function.

The National Science Foundation (NSF) Division of Chemical, Bioengineering, Environmental and Transport Systems (CBET), seeks proposals that elucidate mechanisms of, and develop strategies to, direct the differentiation of undifferentiated cells into mature, functional cells or organoids. Projects responsive to this solicitation must aim to establish a robust and reproducible set of differentiation design rules, predictive models, real-time sensing, control, and quality assurance methods, and integrate them into a workable differentiation strategy. They must develop a fundamental understanding of how cells develop, including mechanisms, molecular machinery, dynamics, and cell-cell interactions, and use this understanding to manipulate cells purposefully. Investigators can choose any undifferentiated cell type, from any animal species, as a starting point and choose any appropriate functional product (cell, organoid, etc.) with real-world relevance. This solicitation parallels NSF's investment in Understanding the Rules of Life (URoL): Predicting Phenotype, NSF's Big Idea focused on predicting the set of observable characteristics (phenotype) of an organism based on its genetic makeup and the nature of its environment and applies it to understanding and accomplishing the intentional and guided differentiation of an undifferentiated cell into cells, organoids or tissues with predetermined activities and functions.

The National Science Foundation (NSF) Division of Chemical, Bioengineering, Environmental and Transport Systems (CBET), seeks proposals that elucidate mechanisms of, and develop strategies to, direct the differentiation of undifferentiated cells into mature, functional cells or organoids. Projects responsive to this solicitation must aim to establish a robust and reproducible set of differentiation design rules, predictive models, real-time sensing, control, and quality assurance methods, and integrate them into a workable differentiation strategy. They must develop a fundamental understanding of how cells develop, including mechanisms, molecular machinery, dynamics, and cell-cell interactions, and use this understanding to manipulate cells purposefully. Investigators can choose any undifferentiated cell type, from any animal species, as a starting point and choose any appropriate functional product (cell, organoid, etc.) with real-world relevance.This solicitation parallels NSF's investment inUnderstanding the Rules of Life (URoL): Predicting Phenotype, NSF's Big Idea focused on predicting the set of observable characteristics (phenotype) of an organism based on its genetic makeup and the nature of its environment and applies it to understanding and accomplishing the intentional and guided differentiation of an undifferentiated cell into cells, organoids or tissues with predetermined activities and functions.

This Funding Opportunity Announcement (FOA) is soliciting applications to develop Solid Oxide Fuel Cell Technology in order to support fuel cells system manufacturers in addressing issues related to cost and reliability of fuel cells systems. Applications are sought in two areas of interest (AOI) that include AOI 1 - Solid Oxide Fuel Cells (SOFC) Core Technology Research and AOI 2 - Core Technology Research and Development (R&D) in Support of Near-Term SOFC Power Systems Prototype Tests. AOI 1 is supporting transformational technologies that are focused on early-stage laboratory-scale R&D. Successful projects will result in validation of concepts at a laboratory-scale. Collaboration with a fuel cell system manufacturer is encouraged. AOI 2 will seek projects that address reliability issues facing 2nd Generation SOFC power systems in an operational environment. This AOI will require a team approach where the participation of at least one fuel cell system manufacturer as a prime or a sub-recipient in the team is required. Teams should be able to take the technology developed during the award to the point that it can be validated in an operational system. Fuel cell technology other than SOFC will be considered non-responsive to both AOIs.

This Funding Opportunity Announcement (FOA) requests applications to explore human pancreatic tissues for the discovery of early biomarkers of T1D pathogenesis, the description of specific signaling or processing pathways that may contribute to the asymptomatic phase of T1D, the development of clinical diagnostic tools for the detection and staging of early T1D in at-risk or recently-diagnosed individuals, and/or the identification of therapeutic targets for the development of preventative or early treatment strategies. Successful applicants will join the Consortium on Beta Cell Death and Survival (CBDS), whose mission is to better define and detect the mechanisms of beta cell stress and destruction central to the development of T1D in humans, with the long-term goal of detecting beta cell destruction and protecting the residual beta cell mass in T1D patients as early as possible in the disease process, and of preventing the progression to autoimmunity. The CBDS is part of a collaborative research framework, the Human Islet Research Network (HIRN, https://hirnetwork.org), whose overall mission is to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans. This FOA will only support studies with a primary focus on increasing our understanding of human disease biology (as opposed to rodent or other animal models). This FOA will not accept applications proposing a clinical trial.

The purpose of this Funding Opportunity Announcement [FOA] submitted through the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is to stimulate the development and validation of novel tools and analytical methods to target, identify and characterize non-neuronal cells in the brain. This FOA complements previous and ongoing cell-census and tool development efforts initiated under BRAIN, RFA-MH-14-215 and RFA-MH-14-216, that have focused almost exclusively on neuronal cells. The cutting-edge tools and methods developed under this opportunity should focus specifically on providing improved points of entry into non-neuronal cell-types (glial and vascular) to enable their inventory and characterization within the CNS and help define how these cells interact among each other and with neuronal cells to impact functional circuitries. Plans for validating the utility of the tool/technology/method and demonstrating its advantage over currently available approaches will be an essential feature of a successful application. Tools that can be used in several species or model organisms rather than in a single species are especially desirable.

Cell-based therapies, especially immune cells, have the potential to revolutionize human healthcare in various different contexts, including cancer and personalized medicine. For example, CAR (Chimeric antigen receptor) T-cell therapy for cancer requires modification, in vitro culture and expansion of human T-cells.   Manufacturing of therapeutic cells as the end product presents major engineering challenges.  New therapies and cell-based products depend critically on the development of robust, reliable and reproducible biomanufacturing technologies.

This Funding Opportunity Announcement (FOA) supports the research and development of key early-stage technical challenges for fuel cells and for hydrogen fuel production, delivery and storage, and will leverage the private sector to address institutional barriers that impact progress in the field. The goal of this research activity is to provide affordable, clean, safe, and reliable energy from diverse domestic resources, providing the benefits of increased energy security and reduced emissions through early-stage research and development. The global fuel cell market increased its growth 40% in 2016, with revenues of over $1.6 billion in 2016 and over 20,000 fuel cell units for material handling equipment purchased in the U.S. alone since 2009. Light duty vehicles are an emerging application for fuel cells that has earned substantial commercial and government interest worldwide due to the superior efficiencies, reductions in petroleum consumption, and reductions in criteria pollutants fuel cells make possible.

Fetal bovine serum (FBS) is the most widely used growth supplement for cell culture because it cost-effectively supports the survival and growth of many cell lines. Although serum is an effective growth promotor, it is highly variable in its composition, activity, and physiological effects on cells. This variability introduces inconsistencies into cell culture research. This Funding Opportunity Announcement (FOA) will support STTR projects to develop novel, reliable, and cost-effective tools that will make it easier for researchers to standardize or replace serum in cell culture.

This Funding Opportunity Announcement (FOA) encourages investigator-initiated applications that propose hypothesis-driven research using erythroid cells.  The aim of this program is to support research efforts towards a complete description of the molecular and cellular components of erythropoiesis and how these components function to achieve normal erythropoiesis.  Components include genes that are expressed (transcriptome) in erythroid cells, either during development or during differentiation, chemical changes to DNA and histone proteins (epigenome) and the proteins (proteome) that are translated in erythroid cells, including post-translational modifications or subcellular localizations that are unique to erythroid cells. 

GSK is seeking rapid, point of care analytical tests for gene therapy products that can go from sample to result within 2 hours   Tests should work with human cells at a concentration of 1x106 - 1x108 cells per mL in growth media. They should characterize / quantify the populations of cell immunophenotypes in the sample.   Lab tests are welcome. GSK would be especially interested in analytical techniques that could be carried out at or close to the patient's bedside.

The BMMB Program supports fundamental research in biomechanics and mechanobiology. An emphasis is placed on multiscale mechanics approaches in the study of organisms that integrate across molecular, cell, tissue, and organ domains. The influence of in vivo mechanical forces on cell and matrix biology in the histomorphogenesis, maintenance, regeneration, and aging of tissues is an important concern. In addition, the relationships between mechanical behavior and extracellular matrix composition and organization are of interest. Funded projects may include theoretical, computational, and experimental approaches. The program encourages the consideration of diverse living tissues as smart materials that are self-designing.

The BMMB Program supports fundamental research in biomechanics and mechanobiology. An emphasis is placed on multiscale mechanics approaches in the study of organisms that integrate across molecular, cell, tissue, and organ domains. The influence of in vivo mechanical forces on cell and matrix biology in the histomorphogenesis, maintenance, regeneration, and aging of tissues is an important concern. In addition, the relationships between mechanical behavior and extracellular matrix composition and organization are of interest. Funded projects may include theoretical, computational, and experimental approaches. The program encourages the consideration of diverse living tissues as smart materials that are self-designing.

The Cellular and Biochemical Engineering (CBE) program supports fundamental engineering research that advances the understanding of cellular and biomolecular processes in engineering biology and eventually leads to the development of enabling technology for advanced biomanufacturing in support of the therapeutic cells, biochemical, biopharmaceutical and biotechnology industries.  A quantitative treatment of biological and engineering problems of biological processes is considered vital to successful research projects in the CBE program.  Fundamental to many research projects in this area is the understanding of how biomolecules, cells and cell populations interact in the biomanufacturing environment, and how those molecular-level interactions lead to changes in structure, function, and behavior.  The program encourages highly innovative and potentially transformative engineering research leading to novel bioprocessing and biomanufacturing approaches, and proposals that address emerging research areas and technologies that effectively integrate knowledge and practices from different disciplines while incorporating ongoing research into educational activities.

U.S. Department of Energy Advanced Research Projects Agency - Energy Announcement of Teaming Partner List for Upcoming Funding Opportunity Announcement: Reliable Electricity Based on Electrochemical Systems (REBELS) The Advanced Research Projects Agency Energy (ARPA-E) intends to issue a Funding Opportunity Announcement (FOA) entitled Reliable Electricity Based on Electrochemical Systems (REBELS) to solicit applications for financial assistance to fund new intermediate temperature fuel cell (ITFC) technologies that efficiently generate stationary power from fossil fuels in the near-term, while simultaneously building a bridge to a zero carbon future. Currently, ARPA-E anticipates that there will be three specific areas of interest indentified in the REBELS FOA as follows: (1) low-cost, efficient, reliable ITFCs for small distributed generation applications, (2) ITFCs that are capable of in-situ charge storage in an electrode to enable battery-like response to transients, and (3) electrochemical devices that produce liquid fuels from methane using excess renewable resources. Fuel cell systems based on existing Department of Energy R&D programs, such as low temperature polymer exchange membrane (LT-PEM) and high temperature solid oxide fuel cells (HT-SOFCs), will not be areas of interest for the anticipated REBELS FOA. 

This Funding Opportunity Announcement (FOA) invites applications from institutions and organizations to conduct research focused on elucidating mechanisms of Fc-dependent, antibody-mediated killing of infected or aberrant cells, or antibody-mediated therapeutic ablation of cells implicated in immune pathologies, including autoimmune and allergic diseases. Studies supported by this FOA are expected to define variables that affect efficiencies of antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cell-mediated phagocytosis (ADCP), both in vitro and in vivo. U01 awardees will be expected to attend annual Program Progress/Steering Committee meetings and present progress to fellow awardees and to NIAID program staff. The goal of the meetings is to facilitate collaborations between funded investigators and to accelerate development of mechanistic models that incorporate the collective findings of this program. Advances in our understanding of these Fc-dependent killing mechanisms will inform more efficient design and optimization of ablative antibody therapeutics and may also inform design of vaccines that preferentially elicit ADCC- or ADCP-efficient antibody responses. This FOA uses the U01 grant mechanism, while the companion FOA, PA-19-xxx, uses the R21 mechanism. High risk/high reward projects with limited preliminary data or utilize existing data may be most appropriate for the R21 mechanism.

The Cellular and Biochemical Engineering (CBE)program is part of the Engineering Biology and Health cluster, which also includes 1) Biophotonics; 2) Biosensing; 3) Disability and Rehabilitation Engineering; and 4) Engineering of Biomedical Systems. TheCellular and Biochemical Engineering program supports fundamental engineering research that advances understanding of cellular andbiomolecular processes in engineering biology. CBE-funded research eventually leads to the development of enabling technology for advanced biomanufacturing in support of the therapeutic cell, biochemical, biopharmaceutical, and biotechnology industries. Fundamental to many research projects in this area is the understanding of how biomolecules, subcellular systems, cells, and cell populations interact in the biomanufacturing environment, and how those interactions lead to changes in structure, function, and behavior. A quantitative treatment of problems related to biological processes is considered vital to successful research projects in the CBE program. The program encourages highly innovative and potentially transformative engineering research leading to novel bioprocessing and biomanufacturing approaches. The CBE program also encourages proposals that effectively integrate knowledge and practices from different disciplines while incorporating ongoing research into educational activities.

This Funding Opportunity Announcement (FOA) intends to support investigators who have interest and capability to join efforts for the discovery of cell-based chemical probes for novel brain targets. It is expected that applicants will have in hand the starting compounds (validated hits) for chemical optimization and bioassays for testing new analog compounds. Through this FOA, NIH wishes to stimulate research in: 1) discovery and development of novel, small molecules for their potential use in understanding biological processes relevant to the missions of NIMH, NIA, and/or NIDCD; and 2) discovery and/or validation of novel, biological targets that will inform studies of brain disease mechanisms. Emphasis will be placed on projects that provide new insight into important disease-related biological targets and biological processes. The main emphasis of projects submitted under this FOA should be in the discovery of cell-based chemical probes. Applicants interested in developing in vivo chemical probes may wish to apply using the companion R01 mechanism (PAR-17-336).

The Biotechnology, Biochemical, and Biomass Engineering (BBBE) program supports fundamental engineering research that advances the understanding of cellular and biomolecular processes (in vivo, in vitro, and/or ex vivo) and eventually leads to the development of enabling technology and/or applications in support of the biopharmaceutical, biotechnology, and bioenergy industries, or with applications in health or the environment.  Quantitative assessments of bioprocesses are considered vital to successful research projects in the BBBE program.  Fundamental to many research projects in this area is the understanding of how biomolecules and cells interact in their environment, and how those molecular level interactions lead to changes in structure, function, phenotype, and/or behavior.  The program encourages proposals that address emerging research areas and technologies that effectively integrate knowledge and practices from different disciplines, and effectively incorporate ongoing research into educational activities. Research projects of particular interest in BBBE include, but are not limited to: Metabolic engineering and synthetic biology Quantitative systems biotechnology Tissue engineering and stem cell culture technologies Protein engineering/protein design Development of novel "omics" tools for biotechnology applications

The Biotechnology, Biochemical, and Biomass Engineering (BBBE) program supports fundamental engineering research that advances the understanding of cellular and biomolecular processes (in vivo, in vitro, and/or ex vivo) and eventually leads to the development of enabling technology and/or applications in support of the biopharmaceutical, biotechnology, and bioenergy industries, or with applications in health or the environment.  Quantitative assessments of bioprocesses are considered vital to successful research projects in the BBBE program.  Fundamental to many research projects in this area is the understanding of how biomolecules and cells interact in their environment, and how those molecular level interactions lead to changes in structure, function, phenotype, and/or behavior.  The program encourages proposals that address emerging research areas and technologies that effectively integrate knowledge and practices from different disciplines, and effectively incorporate ongoing research into educational activities. Research projects of particular interest in BBBE include, but are not limited to: Metabolic engineering and synthetic biology Quantitative systems biotechnology Tissue engineering and stem cell culture technologies Protein engineering/protein design Development of novel "omics" tools for biotechnology applications