Funding Opportunity RFA-NS-17-012 from the NIH Guide for Grants and Contracts. The purpose of this funding opportunity announcement (FOA) is to invite applications that address the unmet need to detect cognitive impairment, including dementia, in large and diverse populations seen in primary care across the United States, including in health disparities populations, when a patient, relative, or care provider indicates concern. Proposed clinical paradigms should utilize tools that are simple to use, standardized, and ideally take five minutes or less to administer in a primary care clinical setting.

Funding Opportunity RFA-DA-18-001 from the NIH Guide for Grants and Contracts. The NIDA Avant-Garde Award Program for HIV/AIDS Research supports individual scientists of exceptional creativity who propose high-impact research that will open new areas of HIV/AIDS research relevant to drug abuse and/or lead to new avenues for prevention and treatment of HIV/AIDS among drug abusers. The term avant-garde is used to describe highly innovative approaches that have the potential to be transformative. The proposed research should reflect approaches and ideas that are substantially different from those already being pursued by the investigator or others and should support the NIH HIV/AIDS Research Priorities https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-137.html. The NIDA Avant-Garde award supports innovative, basic research that may lead to improved preventive interventions or therapies; creative, new strategies to prevent disease transmission; novel approaches to improve disease outcomes; and creative approaches to eradicating HIV or improving the lives of those living with HIV.

Funding Opportunity PAR-17-204 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to support research projects that examine how inter-organelle communication in cancer cells and/or tumor-associated cells affects cellular function, adaptation, and phenotypic plasticity.

Funding Opportunity PAR-17-203 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to support research projects that examine how inter-organelle communication in cancer cells and/or tumor-associated cells affects cellular function, adaptation, and phenotypic plasticity.

Notice NOT-AI-17-016 from the NIH Guide for Grants and Contracts

Funding Opportunity PA-17-197 from the NIH Guide for Grants and Contracts. Despite significant scientific advancements made in substance use disorder research over the last century, the causes and consequences of drug use in later life remain poorly understood. The intent of this funding opportunity announcement is to support innovative research that examines aspects of marijuana and prescription opioid and benzodiazepine use in adults aged 50 and older. This FOA encourages research that examines the determinants of these types of drug use and/or characterizes the resulting neurobiological alterations, associated behaviors, and public health consequences. This initiative will focus on two distinct populations of older adults: individuals with earlier onset of drug use who are now entering this stage of adult development or individuals who initiate drug use after the age of 50. Applications are encouraged to utilize broad methodologies ranging from basic science, clinical, and epidemiological approaches. The insights gleaned from this initiative are critical to our understanding of the determinants of drug use in later life, as well as its consequences in the aging brain and on behavior. This knowledge may have the potential to identify risk factors and to guide clinical practices in older populations.

Funding Opportunity PA-17-198 from the NIH Guide for Grants and Contracts. Despite significant scientific advancements made in substance use disorder research over the last century, the causes and consequences of drug use in later life remain poorly understood. The intent of this funding opportunity announcement is to support innovative research that examines aspects of marijuana and prescription opioid and benzodiazepine use in adults aged 50 and older. This FOA encourages research that examines the determinants of these types of drug use and/or characterizes the resulting neurobiological alterations, associated behaviors, and public health consequences. This initiative will focus on two distinct populations of older adults: individuals with earlier onset of drug use who are now entering this stage of adult development or individuals who initiate drug use after the age of 50. Applications are encouraged to utilize broad methodologies ranging from basic science, clinical, and epidemiological approaches. The insights gleaned from this initiative are critical to our understanding of the determinants of drug use in later life, as well as its consequences in the aging brain and on behavior. This knowledge may have the potential to identify risk factors and to guide clinical practices in older populations.

Funding Opportunity PA-17-196 from the NIH Guide for Grants and Contracts. Despite significant scientific advancements made in substance use disorder research over the last century, the causes and consequences of drug use in later life remain poorly understood. The intent of this funding opportunity announcement is to support innovative research that examines aspects of marijuana and prescription opioid and benzodiazepine use in adults aged 50 and older. This FOA encourages research that examines the determinants of these types of drug use and/or characterizes the resulting neurobiological alterations, associated behaviors, and public health consequences. This initiative will focus on two distinct populations of older adults: individuals with earlier onset of drug use who are now entering this stage of adult development or individuals who initiate drug use after the age of 50. Applications are encouraged to utilize broad methodologies ranging from basic science, clinical, and epidemiological approaches. The insights gleaned from this initiative are critical to our understanding of the determinants of drug use in later life, as well as its consequences in the aging brain and on behavior. This knowledge may have the potential to identify risk factors and to guide clinical practices in older populations.

Funding Opportunity PA-17-202 from the NIH Guide for Grants and Contracts. This FOA encourages applications for research on hearing health care in adults in support of improving access and affordability. Further research is needed to strengthen the evidence base with a goal of delivering better hearing health care outcomes in adults.

Notice NOT-CA-17-034 from the NIH Guide for Grants and Contracts

Notice NOT-DK-17-009 from the NIH Guide for Grants and Contracts

Notice NOT-HD-17-001 from the NIH Guide for Grants and Contracts

Notice NOT-HG-17-001 from the NIH Guide for Grants and Contracts

Notice NOT-CA-17-040 from the NIH Guide for Grants and Contracts

Notice NOT-CA-17-039 from the NIH Guide for Grants and Contracts

Notice NOT-HL-17-491 from the NIH Guide for Grants and Contracts

Notice NOT-HL-17-490 from the NIH Guide for Grants and Contracts

Notice NOT-CA-17-038 from the NIH Guide for Grants and Contracts

Related Articles

Single-cell analysis of mixed-lineage states leading to a binary cell fate choice.

Nature. 2016 Sep 29;537(7622):698-702

Authors: Olsson A, Venkatasubramanian M, Chaudhri VK, Aronow BJ, Salomonis N, Singh H, Grimes HL

Abstract
Delineating hierarchical cellular states, including rare intermediates and the networks of regulatory genes that orchestrate cell-type specification, are continuing challenges for developmental biology. Single-cell RNA sequencing is greatly accelerating such research, given its power to provide comprehensive descriptions of genomic states and their presumptive regulators. Haematopoietic multipotential progenitor cells, as well as bipotential intermediates, manifest mixed-lineage patterns of gene expression at a single-cell level. Such mixed-lineage states may reflect the molecular priming of different developmental potentials by co-expressed alternative-lineage determinants, namely transcription factors. Although a bistable gene regulatory network has been proposed to regulate the specification of either neutrophils or macrophages, the nature of the transition states manifested in vivo, and the underlying dynamics of the cell-fate determinants, have remained elusive. Here we use single-cell RNA sequencing coupled with a new analytic tool, iterative clustering and guide-gene selection, and clonogenic assays to delineate hierarchical genomic and regulatory states that culminate in neutrophil or macrophage specification in mice. We show that this analysis captured prevalent mixed-lineage intermediates that manifested concurrent expression of haematopoietic stem cell/progenitor and myeloid progenitor cell genes. It also revealed rare metastable intermediates that had collapsed the haematopoietic stem cell/progenitor gene expression programme, instead expressing low levels of the myeloid determinants, Irf8 and Gfi1 (refs 9, 10, 11, 12, 13). Genetic perturbations and chromatin immunoprecipitation followed by sequencing revealed Irf8 and Gfi1 as key components of counteracting myeloid-gene-regulatory networks. Combined loss of these two determinants 'trapped' the metastable intermediate. We propose that mixed-lineage states are obligatory during cell-fate specification, manifest differing frequencies because of their dynamic instability and are dictated by counteracting gene-regulatory networks.

PMID: 27580035 [PubMed - indexed for MEDLINE]

Related Articles

Transcriptional Regulation by ATOH1 and its Target SPDEF in the Intestine.

Cell Mol Gastroenterol Hepatol. 2017 Jan;3(1):51-71

Authors: Lo YH, Chung E, Li Z, Wan YW, Mahe MM, Chen MS, Noah TK, Bell KN, Yalamanchili HK, Klisch TJ, Liu Z, Park JS, Shroyer NF

Abstract
BACKGROUND & AIMS: The transcription factor atonal homolog 1 (ATOH1) controls the fate of intestinal progenitors downstream of the Notch signaling pathway. Intestinal progenitors that escape Notch activation express high levels of ATOH1 and commit to a secretory lineage fate, implicating ATOH1 as a gatekeeper for differentiation of intestinal epithelial cells. Although some transcription factors downstream of ATOH1, such as SPDEF, have been identified to specify differentiation and maturation of specific cell types, the bona fide transcriptional targets of ATOH1 still largely are unknown. Here, we aimed to identify ATOH1 targets and to identify transcription factors that are likely to co-regulate gene expression with ATOH1.
METHODS: We used a combination of chromatin immunoprecipitation and messenger RNA-based high-throughput sequencing (ChIP-seq and RNA-seq), together with cell sorting and transgenic mice, to identify direct targets of ATOH1, and establish the epistatic relationship between ATOH1 and SPDEF.
RESULTS: By using unbiased genome-wide approaches, we identified more than 700 genes as ATOH1 transcriptional targets in adult small intestine and colon. Ontology analysis indicated that ATOH1 directly regulates genes involved in specification and function of secretory cells. De novo motif analysis of ATOH1 targets identified SPDEF as a putative transcriptional co-regulator of ATOH1. Functional epistasis experiments in transgenic mice show that SPDEF amplifies ATOH1-dependent transcription but cannot independently initiate transcription of ATOH1 target genes.
CONCLUSIONS: This study unveils the direct targets of ATOH1 in the adult intestines and illuminates the transcriptional events that initiate the specification and function of intestinal secretory lineages.

PMID: 28174757 [PubMed - in process]