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Grant Opportunities

New funding opportunity – 3 years, $1M/year maximum budget, due Sept 1, 2009:

Recovery Act Limited Competition: Biomedical Research, Development, and Growth to Spur the Acceleration of New Technologies (BRDG-SPAN) Pilot Program (RC3)

Download the entire list of NIH Challenge Grant topics (PDF, 2MB)

Of particular note are the following topics which could be of interest to potential users of the Nano eNabler System:

13-AR-101 Biomaterials for Wound Healing.

The inability of chronic wounds to heal is a major health problem in the United States, and the problem will increase in magnitude as the population ages. Understanding and controlling the regenerative process is essential; the natural wound healing response is “over-exuberant” and can create additional morbidity in the form of hypertrophic scarring and fibrosis. There is tremendous interest in developing methods to attract endogenous cells to the wound site to mediate the healing processes; to conduct exploratory work to evaluate new scaffolds and biomaterials that may allow identification of cell populations migrating to the wound edge, and enhance homing and residency of endogenous cells. Other studies of interest include investigation of materials to deliver cells, growth factors, cytokines, or other agents and the use functional bonds to regulate release of these factors. Contact: Dr. Susana Serrate-Sztein, 301-594-5032, NIAMShelp-NIHChallengeGrants@mail.nih.gov

04-CA-101 Enhanced Infrastructure for Brain Cancer Research.

Progress in the treatment of brain metastases has been hampered by a lack of focus on the clinical problem over many years. The most critical need is for coordinated efforts toward creating infrastructure for biospecimen collection, banking, and distribution of clinically annotated tissue available for research focused on all aspects of the process by which a tumor cell metastasizes to the brain are needed. Multidisciplinary approaches should be encouraged to explore: the molecular signature of tumors that metastasize to the brain, homing of tumor cells to the brain microenvironment, the blood brain barrier, the role of brain microenvironment in successful growth of brain metastases and the use of novel imaging and other technologies to target and validate novel therapeutics. Contact: Dr. Judy Mietz, 301-496-9326, mietzj@mail.nih.gov

06-AG-107 Measuring the body burden of emerging contaminants: Biosensors and lab-on-a-chip technology for measuring in vivo environmental agents.

New advances in biosensors and lab-on-chip technology create novel ways to measure the body burden and sub-clinical health effects of emerging contaminants in the environment in large study populations. Additional research funds would support field testing of the most promising sensors and analysis techniques through collaboration with existing epidemiologic studies taking advantage of both new and banked tissue specimens.

Contact: Ms. Winifred Rossi, 301-496-3836, RossiW@mail.nih.gov

06-AG-108 Technologies for obtaining genomic, proteomic, and metabolomic data from individual viable cells in complex tissues.

Develop technologies that are able to use one or a small number of cells are needed to generate data to understand the molecular phenotype, or state, of a particular cell type and the role it plays in tissue and organ function in health and disease.

Contact: Dr. Jose Velazquez, 301-496-6428, Jvelazqu@mail.nih.gov

06-AI-101 Development of novel ideas for diagnostic and assay platforms for use in clinical and field conditions

Approaches may include microsampling and high throughput cellular immune assays. Contact: Dr. Maria Giovanni, 301-496-1884, mgiovanni@mail.nih.gov

06-CA-103 Synthetic biology.

As we increase our understanding of cancer we find ourselves in a unique position to re-engineer or manipulate fundamental cellular processes in an attempt to control and treat the disease. This type of approach would require an interdisciplinary effort between cancer biology and engineering principals to interrogate, target and integrate at subcellular and cellular levels to generate model synthetic biological systems.

Contact: Dr. Dan Gallahan, 301-496-8636, gallahad@mail.nih.gov

06-CA-107 In vivo molecular profiling (spatial relationships) and single cell analysis.

A great deal of information has been gained through molecular profiling of cancer cells and specimens. But these profiles, patterns of gene or protein expression for example, have been identified by monitoring purified components. The context and timing of the expression of these molecules is also important and spatial changes in protein and other molecules are often important in the development of cancer. New methods for visualizing gene expression, proteins or other molecules in normal and cancer cells are needed. Methods for single molecule resolution and methodologies that can monitor expression over time in vivo are needed. Contact: Dr. Jennifer Couch, 301-435-5226, couchj@mail.nih.gov

06-CA-113 Pre-Clinical Diagnostic and Prognostic Technologies for the Early Detection of Cancer.

Technologies intended for pre-clinical cancer detection and diagnostics, prediction of progression from preneoplastic lesions to cancer, early detection of cancer, and technologies for risk assessment are badly needed to facilitate the early, effective, and more accurate detection of cancer. Specific technologies of interest include technologies and associated methods to significantly improve cancer biomarker discovery, multiplexing platforms to accurately measure low abundance biomarkers, including those from bodily fluids (serum, plasma, buffy coat cells, urine, sputum, saliva) or cells within these fluids, integrated technological platforms for enabling multiplexed biomarker assays, and cellular imaging technologies to detect preneoplastic lesions. Contact: Dr. Richard Aragon, 301-496-1550, raragon@mail.nih.gov

06-CA-114 Integrated Clinical Technologies.

Novel devices, instrumentation, and tools intended for potential clinical application and those for the prediction of response to therapy or for therapy monitoring are needed to facilitate improved clinical outcomes. Such technologies include platforms for comprehensive, high throughput analysis of genomic or proteomic alterations of tumor tissue such as changes in epigenetic profiles, gene copy number, gene expression, post-translational modifications, and tumor-related changes in lipids and carbohydrates. Of particular utility will be the integration of varying technologies for the development of analytical or point of care devices, including microfluidics, nanotechnology, micro or nanofabrication devices, or the multiplexing thereof. Technologies designed for the targeted delivery and retention of anticancer agents or for the surveillance or monitoring of such agents are also needed to facilitate better interventions for cancer treatment and diagnosis.

Contact: Dr. Richard Aragon, 301-496-1550, raragon@mail.nih.gov

06-CA-116 Physical Sciences and Cellular Mechanics.

Technologies designed to elucidate, interrogate, and model the role of physical forces on varying cellular functions, including cellular metastasis, metastatic potential, or motility need to be developed in order to facilitate an increased understanding of the role that physical forces play in cancer pathology and metastasis. Of particular need are technologies to quantitatively and temporally model, monitor, track, and/or characterize changes that occur at the level of the cell, including the development of cell-based bio and nanosensors. Technologies for targeted measurements made at the level of the cell, including cell-cell adhesion, cellular motility, and/or cellular adherence properties are also of interest, as are technologies to quantitatively measure cytoskeletal changes and the impact of such changes on elements of metastatic potential, including increased/decreased motility, changes in intracellular mechanics, and ability of cells to interact with the environment.

Contact: Dr. Jerry S. Lee, 301-496-1045, leejerry@mail.nih.gov

06-AC-117 Cancer Development, Pathology, and Pathological Progression.

Technologies that provide new tools and insights for basic research with increased speed, cost efficiency, sensitivity, selectivity, or the capability to create new avenues of research into the specific mechanisms can lead to a better understanding of the development and progression of cancer. Of interest are technologies for molecular, subcellular, cellular and extracellular structure/function studies; capture, separation, and characterization of biomolecules, molecular complexes, sub-cellular complexes, cells, and complex mixtures; and technologies to facilitate the development of more accurate in vitro and in vivo cancer models (especially mouse models for human cancers). Of specific interest are new technologies that enhance understanding of the tumor microenvironment, cancer stem cells, complex pathways, and the role of pathogens in cancer development.

Contact: Dr. Richard Aragon, 301-496-1550, raragon@mail.nih.gov

06-DA-102 Tool Development for the Neurosciences.

Tools that unambiguously identify, manipulate, and report from neurons in vivo and in vitro are needed to help us understand interactions within neural circuits, to examine the functions of types of neurons that are derived from different brain regions, and to determine how selective and conditional silencing or activation of individual neurons or groups of similar neurons may alter functional outcomes, including behavior. This methodology can contribute greatly to the identification of real-time responses to drugs of abuse or to therapeutic interventions, and can play a key role in helping us understand endogenous neuroprotective mechanisms and the repair of frank brain damage or neural dysfunction as a result of drug abuse.

Contact: Dr. Nancy Pilotte, 301-435-1317, npilotte@nih.gov

06-ES-101* Measuring the body burden of emerging contaminants: Biosensors and lab-on-a-chip technology for measuring in vivo environmental agents.

New advances in biosensors and lab-on-chip technology create novel ways to measure the body burden and sub-clinical health effects of emerging contaminants in the environment in large study populations. Additional research funds would support field testing of the most promising sensors and analysis techniques through collaboration with existing epidemiologic studies taking advantage of both new and banked tissue specimens.

Contact: Dr. David Balshaw, 919-541-2448, Balshaw@niehs.nih.gov

06-ES-102* 3-D or virtual models to reduce use of animals in research: Creation of miniature multi-cellular organs for high throughput screening for chemical toxicity testing.

Development of novel micro-scale systems of multiple cell types that replicate the macro-scale structure and function of major organ systems in response to environmental stressors linked with development of computational models of organ system function can accelerate testing of the multitude of chemicals in our environment for toxicity. Research which furthers the generation of 3-D biological models will provide new assays for rapid screening of toxicity in organs such as the lung and liver. Cell types, such as human stem cells, used in these systems would reduce the use of animals and improve our assessment of chemical hazards in the environment.

Contact: Dr. David Balshaw, 919-541-2448, Balshaw@niehs.nih.gov

06-GM-112 Molecular and Cellular Dynamics Technologies

Development of tools, reagents, and technologies to better understand molecular and cellular dynamics in vivo. The goal is to develop the capability to characterize the abundance, location, composition, interactions, and turnover of individual molecules with high sensitivity and with little perturbation of the cellular environment. New methods, including those for single-molecule resolution, are needed for tracking and recording these changes in vivo at the subcellular level.

Contact: Dr. Catherine Lewis, 301-594-0828, lewisc@nigms.nih.gov

06-HD-102 Point of Care Diagnosis and Assessment.

Development of rapid point-of-care diagnosis could result in dramatic improvements in targeted therapy, outcomes, and cost of care. Research is needed to jumpstart the development and application of these techniques, particularly for newborn screening and diagnosis of serious conditions in infants. Examples of NICHD’s interest in this area include:

o Nanotechnologies and Microfluidics for Newborn Screening

– Proof-of-concept projects are needed for new technologies, based on, but not limited to, micro- and nanofluidic and nanostring technologies, that pioneer reliable diagnostic approaches and tools for assessing

1) gene expression in small, well defined samples at specific developmental stages;

2) multiple analytes rapidly and efficiently with minimal-volume human specimens, pertaining to a broad range of early detectable developmental disabilities;

3) sepsis in newborns.

o Assessment of HIV and CD4 Counts in Infants

– Diagnosis of HIV infection in infants involves direct assessment of the virus, and CD4 counts are needed for immune assessment in HIV; however, both require technology that does not lend itself to point of care assessment. New techniques need to be developed to facilitate early diagnosis and immediate treatment in infancy, particularly in low resource settings.

o Hemoglobinopathies and thalassemias – Digital microfluidics technology offers the hope for quick diagnosis, assessment and monitoring of hemoglobinopathies and thalassemias, to speed infant, children and other patients’ access to appropriate treatment.

Contact: Dr. James Coulombe, 301-451-1390, UCoulombeJ@mail.nih.govU;

Dr. Tiina Urv, 301-402-7015, Uurvtiin@mail.nih.govU;

Dr. Lynne Mofenson, 301-435-6870, Umofensol@mail.nih.govU;

Dr. Tonse Raju, 301-402-1872, Urajut@mail.nih.govU

06-HG-102* Technologies for obtaining genomic, proteomic, and metabolomic data from individual viable cells in complex tissues.

Most existing technologies can only measure the properties of a population of cells and not the properties of individual cells. Technologies that are able to use one or a small number of cells are needed to generate data to understand the molecular phenotype, or state, of a particular cell type and the role it plays in tissue and organ function in health and disease.

Contact: Dr. Brad Ozenberger, 301-496-7531, bozenberger@mail.nih.gov

06-HG-104 New Technology and Resources for Personalized Medicine.

To make personalized medicine a reality requires new technologies and resources, such as rapid point-of-care genotyping methods and more effective ways to use genetic testing results in conjunction with electronic medical records. Research on the effects that the utilization of such resources has on health costs and outcomes is also urgently needed to achieve the full integration of personalized medicine into current health care systems.

NHGRI contact: Dr. Ebony Bookman, 919-541-0367, bookmane@mail.nih.gov

06-NS-103 Breakthrough Technologies for Neuroscience.

Advances in basic neuroscience are often catalyzed by the development of breakthrough technologies that allow interrogation of nervous system function (e.g. patch clamp recording from single cells, optical imaging, multi-channel recording arrays, fluorescent dyes to image cell types and intracellular processes, etc.). The challenge is to develop new technologies with the potential to enable basic neuroscientists to make future quantum leaps in understanding nervous system development and function.

Contact: Dr. Edmund Talley, 301-496-1917, talleye@ninds.nih.gov

06-OD-109 3D Tissue High Throughput Screening Platforms.

Engineered three dimensional human tissue models are needed to rapidly evaluate, with high fidelity, the safety and efficacy of drug candidates in a cost-effective manner. A critical challenge is to make a modular three dimensional tissue system that can accommodate multiple tissue types compatible with high throughput screening platforms.

Contact: Dr. Rosemarie Hunziker (NIBIB), 301-451-1609, hunzikerr@mail.nih.gov

11-AR-102 Basic Studies on Regenerative Medicine/Tissue Engineering and Wound Repair.

The objectives are to define differences in molecular pathways in healing versus non-healing wounds, in acute versus chronic tissue (skin, joint) damage, and in the pathways that regulate the integration of muscle, tendon and bone into functional units.

NIAMS Contact: Dr. Joan McGowan, 301-594-5055, NIAMShelp-

NIHChallengeGrants@mail.nih.gov

11-DE-101 Craniofacial Tissue Regeneration.

Every hour, a baby is born with a craniofacial birth defect that requires complex surgical correction. In addition, numerous procedures are performed each year for maxillofacial reconstruction following head and neck cancer surgery, and trauma and injuries from accidents, violence, and, more recently, combat. Technological advances present the timely research opportunity to promote craniofacial tissue regeneration using bioengineering and biomimetic approaches. ;A5F: Design of strategies to promote craniofacial tissue regeneration using bioengineering and biomimetic approaches, including the development of novel biomaterials and scaffolds, directed differentiation of stem and progenitor cells, modulation of mechanical and other physical properties of tissues to guide their morphogenesis, control of the wound healing microenvironment, tissue printing and local delivery of therapies.

Contact: Dr. Nadya Lumelsky, 301-594-7703, Nadya.Lumelsky@nih.gov

11-EB-101* Vascular Networks in Engineered Tissues.

Research on the design, optimization, and formation of a complete vascular network capable of delivering oxygen and nutrients and removing waste products in engineered tissues (i.e., vascularization of engineered tissue constructs).

Contact: Dr. Rosemarie Hunziker, 301-451-1609, hunzikerr@mail.nih.gov

11-EB-102 Advanced Biomaterials to Support Engineered Tissues.

The critical role of cell-matrix interactions in designing functional engineered tissues is increasingly appreciated. Scaffolds need to be: biocompatible (i.e. non-immunogenic, non-toxic, able to fully integrate with existing structures), biomechanically robust (i.e. capable of withstanding a wide array of stresses and strains), biomimetic (i.e. approximating the function of a target tissue as well as the native structure—at the nano- through macro- scales), complex (i.e. incorporating spatial-temporal-structural gradients as needed), and appropriately biodegradable (i.e. decomposing into non-toxic component parts as host remodeling occurs). Proposals addressing novel structural aspects of known materials, or the development of new synthetic or natural materials are encouraged.

Contact: Dr. Rosemarie Hunziker, 301-451-1609, hunzikerr@mail.nih.gov

11-EB-103 Modular Platforms for Regeneration and Development.

Current state-of-the-art for assessing the developmental/differentiation potential of a stem cell involves transplantation to an animal, waiting, and a full histological and physiological analysis upon autopsy. This process is slow, cumbersome, costly, and unwieldy. In vitro tissue models offer a more reliable system with tighter control, greater access to spatio-temporal variables, and many other advantages. Stem cells can be introduced into the basic tissue model platform to study development and how specific interventions affect outcomes becomes more accessible. Such surrogate developmental assays can establish a new toolkit for “tissueomics”—the collection and analysis of complex, multi-scale, rigorous, structured, quantitative data at the tissue level.

Contact: Dr. Rosemarie Hunziker, 301-451-1609, hunzikerr@mail.nih.gov

11-EB-104 Living Human Tissue Microarrays.

Prototypes of vitro tissue models of target organs (e.g. skin, liver, lung, muscle) currently exist. However, these systems are not user-friendly, robust, or flexible—preventing their use for high throughput assays that would underlie the next generation of drug/toxicity screening systems for predicting human tissue responses. Proposals are invited to Generate organotypic platforms that are complex yet modular, hardened, standardized, simplified, and validated against traditional animal models.

Contact: Dr. Rosemarie Hunziker, 301-451-1609, hunzikerr@mail.nih.gov

11-EB-105 Advanced Imaging Systems for Tissue Engineering.

The ability to monitor complex cell-cell and cell-matrix interactions in engineered tissues in vitro and in vivo is critically important. The imaging needs to be functional—able to assess meaningful changes non-destructively and non-invasively; intrinsic—using inherent signatures of normal biological processes (e.g. intermediates of energy metabolism, conformationally based changes in light scattering); and dynamic—monitoring events as they are occurring. Proposals to develop tools for characterizing engineered tissues in vitro and in vivo are encouraged.

Contact: Dr. Rosemarie Hunziker, 301-451-1609, hunzikerr@mail.nih.gov

11-EB-106 Technologies for Expanding Stem Cells and Producing Engineered Tissue.

Tissue engineering and regenerative medicine is a rapidly evolving field, but current production and manufacturing technologies are confined to the laboratory scale and grossly inadequate to ensure sufficient quantity and quality on an industrial scale. New measurement tools, and engineering methods and design principles that can model, monitor, and influence the interaction of cells and their environment at the molecular and organelle level are urgently needed. Projects are sought to develop scaleable bioreactors to precisely control the chemical and mechanical environment for functional 3D tissue growth or for rapidly expanding stem cells; quantitative, non-invasive tools to monitor structure, composition, quorum sensing, and function of heterogeneous tissues in real time; and technologies for preservation, sterilization, packaging, transport, and ensuring cell and tissue health and phenotypic stability.

Contact: Dr. Albert Lee, 301-451-1317, leeah@mail.nih.gov

13-CA-101 Cellular Mechanics.

A great deal of information about cancer has come to light through the generation of molecular data, including gene and protein expression data that differs between cancer and normal cells. But also of critical importance is the mechanics of the cells themselves: adhesion strength, motility, and shape deformation changes have all been identified in cancer cells compared to normal. High throughput methods for capturing the physical properties of cells are needed to help complete our understanding of cancer processes.

Contact: Dr. Randy Knowlton, 301-435-5226, knowltoj@mail.nih.gov

13-CA-102 Nanotechnology-based multi-functional materials for theranostic applications.

Nanotechnology provides a unique opportunity to develop multi-functional constructs carrying targeting moiety, therapeutic construct, and imaging agent. Such constructs will enable entirely new category of clinical solutions which permit early recognition of the disease through the use of novel contrast agents combined with one of the existing imaging modalities (MRI, ultrasound, optical imaging) followed through tailored release of the therapeutic. This new category of solutions – theranostic will provide a path for personalized medicine in oncology.

Contact: Dr. Piotr Grodzinski, 301-496-1550, grodzinp@mail.nih.gov

13-DK-103 Scaffolds, biomatrices, smart materials.

Examples: Development of novel biomaterials, scaffolds, and biomatrices that may modulate cellular behavior, differentiation, and engraftment to optimize cellular replacement therapies and tissue engineering; Development of smart biomaterials, implantable biohybrids matrices or membranes that may release bioactive agents that promote vascularization, innervation, or inhibit the inflammatory/fibrotic response thus improving biocompatibility and durability.

Contact Dr. Guillermo Arreaza, 301-594-4724, arreazag@mail.nih.gov.

14-CA-101 Tumor Stem Cells

The role of cancer stem cells remains a controversial and poorly understood area of biology. Some of the pending questions include: the existence and characteristics of tumor stem cells in different tissue types; the relationship between stem cells, tumor cells and dormant cells; role of the microenvironment in the development and harboring of stem cells; the effect of cancer stem cells on treatment.

Contact: Dr. Allan Mufson, 301-496-7815, mufsonr@mail.nih.gov

14-CA-102 Understanding the Heterogeneity of Cancer and its Environment.

Cancer is not a disease of a single cell but multiple cells interacting in a timely way to develop and progress through the cancer continuum. These cells make up the greater cancer micro-environment and can include transformed cells, tumor stem cells, differentiating cells and associated stromal cells. Efforts are needed to identify and characterize this cellular milieu so that we can better understand the biology.

Contact: Dr. Suresh Mohla, 301-435-1878, mohlas@mail.nih.gov

14-DE-103 Enhancing Human Embryonic Stem (ES) Cell Culture Systems.

Cell differentiation and tissue morphogenesis during normal development is guided by the highly orchestrated temporal, spatial and combinatorial action of multiple of ligands, signaling pathways, transcription factors, and extracellular matrices. In light of this tremendous complexity, the existing human ES cell in vitro culture systems lack appropriate sophistication thus necessitating the need for strategies to better mimic normal developmental processes. Recent progress in the fields of bioengineering, nanotechnology, biomaterials and bioimaging offer a wealth of tools that can lend tight control of the multiple parameters needed to improve the existing human ES culture systems. Integration of engineering disciplines with developmental biology and with ES cell technology for deriving a new generation of human ES cell culture protocols that will facilitate the application of ES cell-based therapies for the treatment of a multitude of human tissue degenerative diseases and trauma, including those of oral and craniofacial complex.

Contact: Dr. Nadya Lumelsky, 301-594-7703, Nadya.Lumelsky@nih.gov

14-DK-102 Discovery of Methods to Program Stem or Progenitor Cells.

These methods would allow manipulation of stem or progenitor cells in a predictable manner to differentiate into cells/tissues of NIDDK relevance; such as, hematopoietic cells, bladder, liver, intestine, pancreas, kidney, prostate, etc. Studies may rely upon model organisms with a goal of application to humans.

Contact Dr. Sheryl Sato, 301-594-8811, smsato@mail.nih.gov.

14-ES-101 Effects of Exposures to Pluripotent Cells Growth, Development, and Function.

Tissues that have the potential to differentiate into a variety of cell types during maturation may be especially sensitive to the effects of environmental exposures. Support for research that determines the effects of environmentally relevant exposures on differentiation, proliferation, function and survival of multi-potent cells in targeted tissues during a range of windows of susceptibility would increase our understanding of the cellular targets for insult and how the cells respond during different life stages could provide value insight into both prevention and treatment strategies for a variety of diseases.

Contact: Dr. Les Reinlib, 919-541-4998, Reinlib@niehs.nih.gov

14-HL-102 Bio-models and Scaffolds for Blood Cell Production and Tissue Regeneration.

Stem cells have the potential to serve as a virtually unlimited source of all blood cell lineages for use in transfusion medicine, other cellular therapies, and tissue regeneration. Generation of blood cells of the required lineages and in the required numbers, and tissue regeneration uses spatial cues and tissue topography not reproduced in simple cell culture systems. Advances in stem cell technology and blood cell signaling networks have led us to the point that new bio-models and scaffolds can be developed to regenerate tissues and increase blood cell production to levels needed for clinical applications.

Contact: Dr. John Thomas, 301-435-0065, thomasj@nhlbi.nih.gov