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Additionally, studies that elucidate the underlying mechanisms that result in immune memory and protection in response to vaccination. Topics of interest relevant to immunity to infection and/or vaccination include, but are not limited to:Differentiation and activation of innate and adaptive immune cells and signaling pathways;Positive and negative regulation of inflammation;Mechanisms by which the innate immune system directs subsequent adaptive immune responses;Generation and maintenance of effector and memory antigen-specific T and B lymphocytes;Generation and maintenance of anti-viral effector innate lymphocytes;Regulation of differentiation and maintenance of effector and memory antigen-specific T and B lymphocytes;Migration of na飗e, memory and effector cells during the induction and effector phases of immune responses and their therapeutic modulation;Generation, differentiation and maintenance of tissue-resident antigen-specific lymphocytes;Responses of tissue-resident lymphocytes to microbial and/or viral infections;Regulation of antibody production and mechanisms of antibody-mediated protectionDefinition of biomarkers of protective immune responses;Characterization of innate and adaptive mucosal immune responses;Relationship between mucosal immunity and the development of, or protection from, autoimmune disease;Mechanisms of immune-mediated pathogenesis triggered by responses to microbial and/or viral infection;Effect of viral and microbial infections, and environmental pollutants on systemic/regional innate immunity and epithelial/mucosa functions and their contribution to the pathogenesis of asthma, allergic diseases, or autoimmune diseases, and the relationship to commensal microbiota.NIAID - Infectious Diseases (non-HIV/AIDS):Research on infectious diseases (non-HIV/AIDS) should focus on malaria, tuberculosis, dengue fever, enterovirus 71, rabies, schistosomiasis, measles, hepatitis, or influenza and include one of the following areas:Antimicrobial resistance, including mechanisms of resistance;Resistance in disease vectors;Immune responses to infectious diseases or vaccines, including the role of immune responses in pathogenesis;Molecular characteristics of innate immunity in acute or chronic infections and strategies for modulation of the immune responses.NCI - Cancer: Applications should be focused in the following areas:Genomics/Proteomics (e.g., collaborative research leveraging proteomic data publicly released by NCI抯 Clinical Proteomics Tumor Analysis Consortium [CPTAC]) that has been analyzed as part of The Cancer Genome Atlas (TCGA));Nanotechnology (e.g., collaborative research focused on translating genomic targets into cancer therapeutics using nanotechnology and studies on structure-activity relationships in nanomaterials and their safety);Immunotherapy/ new immune inhibitory receptors/co-inhibitory molecules in tumor progress;Liver cancer studies as a result of carcinogen exposure, high fat diets, or high alcohol intake;DNA damage networks as a target for cancer cells; synthetic biology studies of engineered cells to study biological networks; and the effects of lipid addiction on tumor cells. NCI Priorities.燱ithin the areas of cancer, the specific priorities for this FOA include the following aspects:Genomics/Epigenomics/Transcriptomics (including Epitranscriptomics)/ProteomicsMining/leveraging of TCGA data or proposed work to identify and understand genomic landscape of various cancer types梪nderstanding the role(s) of genes, non-coding RNAs, and gene products in tumorigenesis, progression, and metastasis.CPTAC梒oordinated effort to understand molecular basis of cancer by systematically identifying proteins that derive from alterations in cancer genomes. NanotechnologyCollaborative applications that propose the use of nanotechnology to delineate cancer-associated pathways as a means to characterize and functionally validate cancer genomic findings in relevant cell and animal modelsApplications that propose the use of nanotechnology to enable cancer biomarker discovery and validation.Research directed towards uncovering structure-activity relationship in nanomaterials and correlation between nanomaterial properties and their safety profiles would also be supported by this FOA.Nanotechnology for immunotherapy梐pplication thay propose to characterize the physiological parameters of nanostructures targeting mononuclear phagocyte system, such as monocytes, macrophages and dendritic cells. Delivering agonists by targeting innate immune sensing pathways with nanotechnology to improve antigen presentation.Targeting immune regulatory cells (e.g. tumor-associated macrophages) to ameliorate tumor immunosuppressive microenvironment.Developing immunotherapy with nanotechnology to improve conventional therapies.Cell engineeringApproaches using synthetic biology to improve the understanding of biological networks and/or to develop live intelligent agents to test new diagnostic and therapeutic strategies.DNA-damage network as a target in cancer cellsDevelopment of molecule tools and imaging and single-cell and single molecule technology to detect induction , expression and de-construction of molecular complexes that are formed in response to genotoxic therapy a variety of human cancers;Characterization and targeting of DNA repair in cancer stem cells and/or quiescent cancer cells in Go or G1;Establishing the role of DNA damage response communication with the microenvironment induced by cancer therapy (e.g., ionizing radiation) and effects such communication has on resistance to treatment and cancer progression in the face of high levels of DNA damage/replication stress;Exhaustive studies to determine synthetic lethal relationships related to cancer-cell defects in DNA repair or DNA replication for range of human cancers and grades.Liver Cancer 桼esearch questions include:Does the cell of origin influence liver tumor type? Do liver cancer stem cells arise and are they found in all liver tumors?What is the role of the hepatic stellate cell in cancer progression?How do individual cell types/stromal components in the microenvironment influence tumor progression.Lipid addiction of cancer cellsThe effects of dietary fat intake/obesity on the activation of fatty acid synthesis in cancer cells;The effects of lipid droplets on the induction of fibrosis.Novel strategies of cancer immunotherapyAmplification/modification爋f爄mmune effectors?e.g., with燙hinese herbs);Recruitment of immune effectors to the tumor site;Targeting爐umor stromal燾ells;Prevention of side effects.Antigen-based design of cellular effectors (e.g. CTL, NK);Cancer vaccine including DC vaccine;Immune molecule monitoring;New immune inhibitory receptors/co-inhibitory molecules in tumor progress.NIMH - Mental Health:Research focused on systems and cellular neuroscience as they relate to mental disorders, including:Use of non-human primates to study neurobiological processes underlying cognitive, social, and affective behavior;Use of non-human primates to create genetic model animals of single-gene disorders beyond Rett syndrome, and to use these models to test gene manipulation methods to subsequently correct the genetic defect in vivo;Research to increase the sophistication of data analyses, (e.g., neuroimaging studies);Development of novel tools and methodologies, including imaging tools and assays, single cell analyses and 憃mics, that allow high throughput phenotyping in cell model systems;Improvements in stem cell techniques to study the molecular and cellular basis of mental disorders;Comprehensively using the imaging genetics in patients or healthy control subjects and the neurobiological characteristics in brain bank tissues, to explore the mechanism of common mental disorders (schizophrenia, autism, etc.).Biologically-relevant computational modeling of neural circuit activity that relates to behavior and/or psychological and cognitive processes in mental health and mental disorders.Research focused on the development of an integrative scientific literature that can inform future, neuroscience-based diagnostic systems, consistent withHYPERLINK "http://www.nimh.nih.gov/research-priorities/rdoc/index.shtml"NIMH抯 Research Domain Criteria爄nitiative.Such studies should include the following elements:Primary hypotheses based on one or more of the defined HYPERLINK "http://www.nimh.nih.gov/research-priorities/rdoc/development-and-definitions-of-the-rdoc-domains-and-constructs.shtml" RDoC domains and constructs;Multiple units of analysis (i.e., genes, molecules, circuits, physiology, behavior, and self-report);Recruitment methods and eligibility criteria that are likely to yield a broad range of severity of the symptoms or problems to be explained, spanning healthy to symptomatic individuals, and avoiding recruitment based strictly on diagnostic criteria;A dimensional approach to data analysis which does not focus only on the extremes of the constructs under investigation.燦ovel, data-based (rather than diagnosis-based) groupings of individuals are acceptable.Research focused on the neurodevelopmental basis of serious mental illness, including:Studies of the prodrome of major mental disorders (e.g. schizophrenia and bipolar disorder);Identification of biomarkers and behavioral markers with predictive values for diagnosis and treatment;Characterization of developmental processes across biological and behavioral systems that give rise to mental illnesses over the lifespan;Determination of sensitive periods and specific factors that modify typical and atypical mental health trajectories;Identification of early biological and environmental risk and protective factors for serious mental illness;Studies of autism, particularly those focused on genomics or early biomarkers, early detection, and/or treatment development.Note: Clinical research is permissible under this FOA, but clinical trials are not. Applicants who wish to conduct a clinical trial focused on mental illness should review information about NIMH抯 new direction for clinical trials research and the relevant FOAs atHYPERLINK "http://www.nimh.nih.gov/funding/opportunities-announcements/clinical-trials-foas/index.shtml"http://www.nimh.nih.gov/funding/opportunities-announcements/clinical-trials-foas/index.shtml. 燙ollectively, these FOAs define NIMH抯 focus on an experimental therapeutics approach when supporting clinical trial research.NINDS:The NINDS will support novel collaborative research projects in the areas of Parkinson's disease (PD) and related disorders, stroke, epilepsy, and vascular contributions to cognitive impairment. Applicants are advised to refer to NINDS policy regarding rigorous study design and transparent reporting and to incorporate these standards into their proposed research,HYPERLINK "http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf"http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf. Research topics include, but are not limited to:Studies in animal models or human subjects to identify genetic and environmental risk factors as well as epigenetic mechanisms in disease or in specific disease subtypes (e.g., PD, intracerebral hemorrhage, intracranial stenosis, small vessel disease or vascular cognitive impairment);Collaborative research that develops, characterizes, validates and utilizes transgenic animal models and large animal models, such as non-human primates in the following areas:Biomarkers of disease mechanisms and progression;Therapeutic targets;Pathophysiological basis of diseases.Collaborative neuroimaging studies for early diagnosis and progression of disease as well as recovery after stroke;Prospective studies on non-motor and cognitive changes in PD and related disorders or cognitive impairment and dementia due to cerebrovascular disease ;Collaborations in database comparison and data sharing as appropriate (e.g., hospital-based and community-based studies of target neurological disorders).Note:燯S applicants who plan to conduct studies on PD and related disorders on US patients should be aware that:All genetic studies are expected to share data via dbGaP (HYPERLINK "http://www.ncbi.nlm.nih.gov/gap"http://www.ncbi.nlm.nih.gov/gap). All laboratory-based PD studies on human specimen and clinical PD biomarker projects, including imaging studies, must be compliant with the PD Biomarkers Program (PDBP) requirements (HYPERLINK "http://grants.nih.gov/grants/guide/notice-files/NOT-NS-11-020.html"http://grants.nih.gov/grants/guide/notice-files/NOT-NS-11-020.html). Specifically, some human biological samples collected under this program may be required to be deposited in the NINDS repository as stated inHYPERLINK "https://grants.nih.gov/grants/guide/notice-files/NOT-NS-15-046.html"https://grants.nih.gov/grants/guide/notice-files/NOT-NS-15-046.html. In addition, all such projects must utilize the PDBP Data Management Resource (DMR) when sharing clinical, imaging and biological data. A detailed plan for data sharing via the DMR is expected to be included in the data sharing plan.When planning, applicants should take into consideration the above policies, and also engage the approval process in China for international sharing of the biological samples and genetic data as appropriate.HIV/AIDS and Co-Morbities:Priority HIV/AIDS topic areas include:Treatment: Improved treatment outcomes, including:Developing and testing novel therapeutic approaches combining virologic-, immunologic-, and cellular-based therapies.Implementation research to ensure early initiation of treatment, adherence to treatment regimens, retention and engagement in these services, and achievement and maintenance of optimal prevention and treatment responses.Prevention: Reducing incidence of HIV/AIDS, including:HIV phylogenetics: Novel applications to identify hotspots of transmission, phylogenic and epidemiologic analyses of HIV dynamics and models of transmission.Vaccine research: AIDS vaccine candidates, including but not limited to identification of candidate novel immunogens, novel adjuvants, or initial characterization of high-risk populations for possible participation in future clinical trials of AIDS vaccines or combination prevention strategies.Co-Morbidities: Improved prevention or treatment of HIV-associated comorbidities, co-infections, and complications, including:Tuberculosis?basic as well as clinical research): Pathogenesis of TB/HIV co-infection, evaluating biomarkers to predict TB disease outcomes (including risk of activating latent infection), and pre-clinical development of novel immune-based therapeutic and prevention modalities for TB/HIV co-infection and disease.Non-infectious comorbidities: Complications associated with long-term HIV disease and antiretroviral therapy, such as cardiovascular and metabolic disorders, neurologic and neurocognitive disorders, and conditions associated with premature aging.AIDS-related malignancies:燬tudies that optimize the diagnosis, prevention and treatment of HIV-associated cancers, including development of biomarkers for early detection, progression, or response to treatment of HIV-associated cancers. Particular interest in virally associated malignancies such as Kaposi sarcoma, lymphoma, and cervical cancer.Cross-Cutting Topics: Other cross-cutting topics include basic research that underpins the development of strategies for the areas listed above; studies focusing on reducing health disparities in the incidence of new HIV infections or in treatment outcomes of people living with HIV/AIDS; and training.Research involving human subjects (clinical research) is permitted under this FOA. For the NIH definition of clinical research versus clinical trials, please see: HYPERLINK "http://funding.niaid.nih.gov/researchfunding/sci/human/pages/default.aspx" http://funding.niaid.nih.gov/researchfunding/sci/human/pages/default.aspx.Note:燼pplicants and collaborating partners are expected to adhere to NIH regulations for the conduct of research involving human subjects and vertebrate animals.Unlike a standard R01 application, preliminary data are not required under this FOA; however, supporting evidence for past productivity, proposed approach, and techniques should be included.Scope of research or activities NOT supported under this FOA:Any clinical trial including clinical trials of drugs, biologics, or diagnostics (see NIH definition of clinical trials in theHYPERLINK "http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_Adobe_VerB.pdf"Application Guide SF424). For NIH definitions of clinical research vs. clinical trials, please seeHYPERLINK "https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html"https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html. 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