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The Division of Molecular and Cellular Biosciences (MCB) supports quantitative, mechanistic, predictive, and theory-driven fundamental research designed to promote understanding of complex living systems at the molecular, subCellular, and Cellular levels. While recognizing the need for thorough and accurate descriptions of biological complexes and pathways, the priority of the Division is to support work that advances the field by capturing the predictive power of mechanistic, quantitative, and evolutionary approaches. Two funding tracks will be available. Core Program Track proposals are solicited to support research relevant to the four MCB core clusters: o Cellular Dynamics and Function o Genetic Mechanisms o Molecular Biophysics o Systems and Synthetic Biology Rules of Life Track proposals that integrate across the scales in biological sciences are solicited to support research that spans from the molecular and Cellular levels normally funded by MCB to organismal and ecosystem scales typically funded by other divisions in the Biological Sciences. This track provides new opportunities to advance our understanding of the Rules of Life by new mechanisms for review and funding of proposals that would not ordinarily fit well within one division in the Biological Sciences Directorate.

The Division of Molecular and Cellular Biosciences (MCB) supports quantitative, predictive, and theory-driven fundamental research and related activities designed to promote understanding of complex living systems at the molecular, subCellular, and Cellular levels. MCB is soliciting proposals for hypothesis-driven and discovery research and related activities in four core clusters: Molecular Biophysics Cellular Dynamics and Function Genetic Mechanisms Systems and Synthetic Biology MCB gives high priority to research projects that use theory, methods, and technologies from physical sciences, mathematics, computational sciences, and engineering to address major biological questions.  Research supported by MCB uses a range of experimental approaches--including in vivo, in vitro and in silico strategies--and a broad spectrum of model and non-model organisms, especially microbes and plants. Typical research supported by MCB integrates theory and experimentation.  Projects that address the emerging areas of multi-scale integration, molecular and Cellular evolution, quantitative prediction of phenome from genomic information, and development of methods and resources are particularly welcome.

Studies funded by our Basic Research RFP will fall into one the following key areas, which are listed in random order: 1. Studies focused on the molecular and biochemical mechanisms regulating SMN expression or mediating SMN function. Results should lead to a better understanding of the requirements for SMN protein biologically, informing therapy development. Such studies may also identify genetic modifiers, upstream regulators of SMN expression / splicing / function, and downstream effectors of SMN functional activity, resulting in novel drug targets.      2.  Studies resulting in greater understanding of the pathophysiology of SMA, using well-validated animal or cellular models of the SMA. This includes focus on the tissue requirements for SMN protein, clarifying the cellular autonomy of the disease in motor neurons and other cells, peripheral versus central manifestations of the disease, and other areas.  3. Early proof-of concept assessment of novel therapeutic approaches for SMA in well-validated animal or cellular models of the disease. 4. Work focused on generating research and clinical trial tools, such as new animal models for SMA, phenotypic cellular assays for SMA, biomarkers or outcome measures for SMA clinical trials, newborn screening protocols, and others.

We envision that studies funded by this Research RFP will fall into one the following key areas: · Studies focused on the molecular and biochemical mechanisms regulating SMN expression or mediating SMN function. Results should lead to a better understanding of the requirements for SMN protein biologically. There is a particular interest in identifying genetic modifiers, upstream regulators of SMN expression / splicing / function, and downstream effectors of SMN functional activity, resulting in new drug targets for SMA. · Studies resulting in greater understanding of the pathophysiology of SMA, using well-validated animal or cellular models of the SMA. This includes focus on the tissue or timing requirements for SMN protein, the cellular autonomy of the disease in motor neurons and other cells, peripheral versus central manifestations of SMA, and others. · Studies focused on early proof-of concept assessment of novel therapeutic approaches for SMA in well-validated animal or cellular models of the disease or on progressing aspects of ongoing preclinical drug programs for SMA towards IND. Proposed SMN enhancing approaches should have advantage over current candidates or have the ability to be used in combination. Particular interest exists in non-SMN based approaches with the potential for combination use with SMN up-regulation strategies. · Work focused on generating research or clinical trial tools for SMA, such as new animal models, phenotypic cellular assays, activity assays for SMN function, biomarkers or outcome measures for clinical trials, and newborn screening protocols / technologies.

This Funding Opportunity Announcement (FOA) solicits grant applications proposing exploratory research projects focused on the early-stage development of highly innovative technologies offering novel molecular or cellular analysis capabilities for basic or clinical cancer research. The emphasis of this FOA is on supporting the development of novel capabilities involving a high degree of technical innovation for targeting, probing, or assessing molecular and cellular features of cancer biology. Well-suited applications must offer the potential to accelerate and/or enhance research in the areas of cancer biology, early detection and screening, clinical diagnosis, treatment, control, epidemiology, and/or address issues associated with cancer health disparities. Technologies proposed for development may be intended to have widespread applicability but must be focused on improving molecular and/or cellular characterizations of cancer biology.

This Funding Opportunity Announcement (FOA) solicits grant applications proposing exploratory research projects focused on further development and validation of emerging technologies offering novel capabilities for targeting, probing, or assessing molecular and cellular features of cancer biology for basic or clinical cancer research. Well-suited applications must offer the potential to accelerate and/or enhance research in the areas of cancer biology, early detection and screening, clinical diagnosis, treatment, control, epidemiology, and/or address issues associated with cancer health disparities. Technologies proposed for development may be intended to have widespread applicability but must be focused on improving molecular and/or cellular characterizations of cancer. FOA Emphasis. This FOA utilizes the R33 mechanism and is suitable for projects, which have overcome major feasibility gaps for the technology or methodology as demonstrated with supportive preliminary data but still require further development and rigorous validation to encourage adoption by the research community. Proposed projects should offer the potential to produce a molecular or cellular analysis capability with a major impact in a broad area of cancer-relevant research.

This Funding Opportunity Announcement (FOA) solicits grant applications proposing exploratory research projects focused on the inception and early-stage development of highly innovative, molecular and/or cellular analysis technologies with transformative potential. The emphasis of this FOA is on supporting the development of novel capabilities involving a high degree of technical innovation for targeting, probing, or assessing molecular and cellular features of cancer biology. Well-suited applications must offer the potential to accelerate and/or enhance research in the areas of cancer biology, early detection, and screening, clinical diagnosis, treatment, control, epidemiology, and/or cancer health disparities. Technologies proposed for development may be intended to have widespread applicability but must focus on improving molecular and/or cellular characterizations of cancer. Applications involving an existing technology not yet demonstrated for the proposed cancer-relevant application(s) are also within the scope of this FOA but must involve additional technical modifications and development to allow for the proposed cancer-relevant context of use or some significant question of feasibility exists for achieving the proposed aims. If the research focus for the application involves an existing technology, a clear description of the feasibility risk justifying the use of the R21 mechanism must be included in the application.  Applicants are encouraged to reach out to the Scientific/Research Contact below with any questions.

The Division of Molecular and Cellular Biosciences (MCB) supports quantitative, mechanistic, predictive, and theory-driven fundamental research designed to promote understanding of complex living systems at the molecular, subCellular, and Cellular levels. While recognizing the need for thorough and accurate descriptions of biological complexes and pathways, the priority of the Division is to support work that advances the field by capturing the predictive power of mechanistic, quantitative, and evolutionary approaches. Proposals are solicited to support research relevant to the four MCB core clusters: Cellular Dynamics and Function Genetic Mechanisms Molecular Biophysics Systems and Synthetic Biology

This Funding Opportunity Announcement (FOA) solicits grant applications proposing exploratory research projects focused on the inception and development of early stage, highly innovative, technologies for the molecular or cellular analysis of cancer. Emerging technologies with significant transformative potential that have not yet been explored in a cancer-relevant use may also be considered. An emerging technology is defined (for the purpose of this FOA) as one that has passed the initial developmental stage, but has not yet been evaluated within the context of cancer-relevant use intended in the application and requires significant modification for the proposed application to establish feasibility. The emphasis of this FOA is on molecular analysis technologies with a high degree of technical innovation with the potential to significantly affect and transform investigations exploring the molecular and cellular bases of cancer. If successful, these technologies would accelerate and/or enhance research in the areas of cancer biology, early detection and screening, clinical diagnosis, treatment, control, epidemiology, and/or cancer health disparities. Technologies proposed for development may be intended to have widespread applicability but must be based on molecular and/or cellular characterizations of cancer.

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.

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.

The Division of Molecular and Cellular Biosciences (MCB) supports quantitative, mechanistic, predictive, and theory-driven fundamental research designed to promote understanding of complex living systems at the molecular, subCellular, and Cellular levels. While recognizing the need for thorough and accurate descriptions of biological complexes and pathways, the priority of the Division is to support work that advances the field by capturing the predictive power of mechanistic, quantitative, and evolutionary approaches. MCB is soliciting proposals in four core clusters:

This Funding Opportunity Announcement (FOA) solicits grant applications proposing exploratory research projects focused on further development and validation of emerging technologies offering novel capabilities for targeting, probing, or assessing molecular and cellular features of cancer biology for basic or clinical cancer research. This FOA solicits R33 applications where major feasibility gaps for the technology or methodology have been overcome, as demonstrated with supportive preliminary data, but still requires further development and rigorous validation to encourage adoption by the research community. Well-suited applications must offer the potential to accelerate and/or enhance research in the areas of cancer biology, early detection and screening, clinical diagnosis, treatment, control, epidemiology, and/or address issues associated with cancer health disparities. Technologies proposed for development may be intended to have widespread applicability but must be focused on improving molecular and/or cellular characterizations of cancer. Projects proposing application of existing technologies where the novelty resides in the biological or clinical target/question being pursued are non-responsive to this solicitation and will not be reviewed. Also listed under R21

The Division of Molecular and Cellular Biosciences (MCB) has developed a new opportunity to enable researchers with a strong track record of prior accomplishment to pursue a new avenue of research or inquiry. This funding mechanism is designed to facilitate and promote a PI's ability to effective adopt empowering technologies that might not be readily accessible in the PI's current research environment or collaboration network.Transformative research likely spans disciplines and minimizing the practical barriers to doing so will strengthen research programs poised to make significant contributions.The award is intended to allow mid-career or later-stage researchers (Associate or Full Professor, or equivalent) to expand or make a transition in their research programs via a sabbatical leave or similar mechanism of professional development and then develop that research program in their own lab. This award will also enable the PI to acquire new scientific or technical expertise, facilitate the investigator's competitiveness, and potentially lead to transformational impacts in molecular and Cellular bioscience. The award would fund up to six months of PI salary during the first sabbatical or professional development year, followed by support for continued research for two subsequent years upon the PI's return to normal academic duties.

The Division of Molecular and Cellular Biosciences (MCB) has developed a new opportunity to enable researchers with a strong track record of prior accomplishment to pursue a new avenue of research or inquiry. This funding mechanism is designed to facilitate and promote a PI's ability to effective adopt empowering technologies that might not be readily accessible in the PI's current research environment or collaboration network. Transformative research likely spans disciplines and minimizing the practical barriers to doing so will strengthen research programs poised to make significant contributions. The award is intended to allow mid-career or later-stage researchers (Associate or Full Professor, or equivalent) to expand or make a transition in their research programs via a sabbatical leave or similar mechanism of professional development and then develop that research program in their own lab. This award will also enable the PI to acquire new scientific or technical expertise, facilitate the investigator's competitiveness, and potentially lead to transformational impacts in molecular and Cellular bioscience.

The Division of Molecular and Cellular Biosciences (MCB) has developed a new opportunity to enable researchers with a strong track record of prior accomplishment to pursue a new avenue of research or inquiry. This funding mechanism is designed to facilitate and promote a PI's ability to effectively adopt empowering technologies that might not be readily accessible in the PI's current research environment or collaboration network. Transformative research likely spans disciplines and minimizing the practical barriers to doing so will strengthen research programs poised to make significant contributions. The award is intended to allow mid-career or later-stage researchers (Associate or Full Professor, or equivalent) to expand or make a transition in their research programs via a sabbatical leave or similar mechanism of professional development and then develop that research program in their own lab. This award will also enable the PI to acquire new scientific or technical expertise, facilitate the investigator's competitiveness, and potentially lead to transformational impacts in molecular and Cellular bioscience.

The purpose of this FOA is to stimulate the development of innovative research strategies aimed at increasing the understanding of the molecular and cellular changes in the cytoskeleton that occur during the aging process.  Applications considering the effect of age on factors such as cytoskeleton structure and function, the impact of the cytoskeleton on intracellular organelle interactions, and signaling or regulatory molecules controlling cellular architecture are encouraged.  There is also interest in studying the role of the cytoskeleton in nuclear-cytoplasmic communications, and in spatio-temporal relationships during the aging process and in age-related diseases.

The participating NIH Institutes and Centers invite applications to address both the origins and the effects of low level chronic inflammation in the onset and progression of age-related diseases and conditions. Chronic inflammation, as defined by elevated levels of both local and systemic cytokines and other pro-inflammatory factors, is a hallmark of aging in virtually all higher animals including humans and is recognized as a major risk factor for developing age-associated diseases. The spectra of phenotypes capable of generating low-level chronic inflammation and their defining mediators are not clear. Further, a clear understanding of how chronic inflammation compromises the integrity of cells or tissues leading to disease progression is lacking. The role of dietary supplements and/or nutritional status in chronic inflammation in age-related disease is also poorly studied. Thus, there is a critical need to establish the knowledge base that will allow a better understanding of the complex interplay between inflammation and age-related diseases. Applications submitted to this FOA should aim to clarify the molecular and cellular basis for the increase in circulating inflammatory factors with aging, and/or shed light on the cause-effect relationship between inflammation and disease, using pre-clinical (animal or cellular based) models.

Research into the etiology and pathophysiology of PD has identified an increasing number of genetic and cellular targets where therapeutic intervention could benefit people with PD, including: Epidemiological studies that have identified both protective and risk factors for PD. Genetic studies that have implicated candidate genes whose protein products may underlie PD pathogenesis. Biochemical studies from cellular and whole organism model systems that point to biological pathways important in PD etiology and pathogenesis, as well as examination of cell death and trophic factor signaling pathways that have pointed to potential protective targets. Emerging understanding of dopamine neuronal development and maintenance in adulthood that has provided potential targets to restore/protect dopaminergic function in PD patients. Improved understanding of the neurochemistry and neurophysiology of the basal ganglia and related neuronal circuits that have suggested ways to alter neuronal function that could help treat motor and non-motor symptoms of PD not addressed by current therapeutics. Better understanding of the physiological and molecular pathways underlying treatment-induced complications that have revealed potential targets for interventions to ameliorate these troubling side effects.

This Funding Opportunity Announcement (FOA) issued by the National Institutes of Health, solicits early stage, high-risk/high-impact applications to develop next-generation tools that distinguish heterogeneous states among cells in situ. Applications should define the current state of technology as a benchmark against which the new tool(s) will be measured and should propose proof-of-concept testing of the tool(s) in a complex biological tissue or living organism. The new tools should provide substantially increased sensitivity, selectivity, spatiotemporal resolution, scalability of multiple global or functional measures of single cells. A particular emphasis for this FOA is on measures that minimize cell perturbation and permit viability of cells for repeated measures over time. These novel technologies will aid in obtaining a fine-grained, integrative and dynamic view of heterogeneous cellular states/classes and will provide innovative platforms to transform research into the cellular basis of diseases.