From Association to Function in the Alzheimers Disease Post Genomics Era (R01)
Department of Health and Human Services
National Institutes of Health
Currently, the AD research community is facing many different challenges between identifying critical AD risk gene variants and elucidating the potential biological and pathological functions of these variants in the initiation and propagation of AD. Protein activity and function are the end game mediators of the effects of AD risk gene variants. For example, gene variants may affect protein-DNA or –RNA interactions, protein translation, or protein complex formation that may be missed by “omics” expression approaches. As a consequence, it is critical to identify and develop more effective ways to rapidly screen variants for impact on potential biological functions prior to any in-depth mechanistic studies. In addition, this initiative also encourages investigators to create a more integrated and effective platform to identify protein-protein interactions, protein complexes and their regulation caused by AD genetic variants. To build on the large amount of genetics and “omics” datasets generated with support from NIA supported GWAS, Alzheimer’s Disease Sequencing Project (ADSP) and other projects, this initiative strongly encourages collaborative and multi-institutional research applications designed to quickly reduce the complexity of GWAS, DNA sequencing and “omics” datasets, either computationally or experimentally; and to provide a robust pipeline to validate the function at the protein level of candidate variants using in vitro and in vivo model systems.
Areas of research interest include, but are not limited to:
Implementation of Proteome-Wide Analysis of disease-associated SNPs (PWAS) on non-protein coding regions to identify allele-specific transcription factor binding and alteration of promoter or enhancer activity in AD. The advantage of using unbiased PWAS for AD research is that it will allow one to link genomic studies to protein function without prior information.
Comprehensive and deep proteomics analyses to understand the impact of GWAS genetic variants; and identify key molecular signatures and networks in modulating the early pathogenesis of AD. Any protein expression profiling analysis solely to generate a large dataset without any functional validation will not be considered responsive.
Test the function of coding genetic variants and to determine the roles of genetic variants or post-translational modifications, cell signaling and protein homeostasis in sporadic AD. Functional analysis can range from biochemical assays to imaging of cells or tissues in various in vitro and in vivo models of sporadic AD.
Implementation of local and web-based in silico model systems to predict the three dimensional structure and function of mutant vs wild type AD risk proteins, particularly if the mutations are located within the protein coding sequence. However, it is expected that any variant function identified by in silico model analysis will need to be confirmed by a complementary in vitro biochemical, cell or animal-based assay.
|Posted Date:||May 11, 2016|
|Last Updated Date:||May 11, 2016|
|Original Closing Date for Applications:||Sep 27, 2016|
|Current Closing Date for Applications:||Sep 27, 2016|
|Archive Date:||Oct 28, 2016|
|Estimated Total Program Funding:||$4,000,000|
Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education
City or township governments
Private institutions of higher education
For profit organizations other than small businesses
Others (see text field entitled “Additional Information on Eligibility” for clarification)
Nonprofits that do not have a 501(c)(3) status with the IRS, other than institutions of higher education
Public and State controlled institutions of higher education
Public housing authorities/Indian housing authorities
Native American tribal organizations (other than Federally recognized tribal governments)
Special district governments
Native American tribal governments (Federally recognized)
Independent school districts
|Additional Information on Eligibility:||Other Eligible Applicants include the following: Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISISs); Eligible Agencies of the Federal Government; Faith-based or Community-based Organizations; Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Indian/Native American Tribal Governments (Other than Federally Recognized); Non-domestic (non-U.S.) Entities (Foreign Organizations); Regional Organizations; Tribally Controlled Colleges and Universities (TCCUs) ; U.S. Territory or Possession.|
|Agency Name:||National Institutes of Health|
|Description:||This Funding Opportunity Announcement (FOA) solicits innovative and collaborative research focused on understanding the structure and function of proteins or protein complexes regulated by different AD genetic variants that have been identified to be associated with the sporadic and late onset Alzheimers disease (AD). Specifically, NIA is interested in identifying and developing more effective and integrated platforms to screen protein functions, protein-protein interaction, protein complexes and their regulation by AD genetic variants prior to any in-depth mechanistic studies. The program encourages collaborative research projects that will translate initial GWAS discovery into functional and phenotypical insights and ultimately lead to understand the complex biology of AD.|
|Link to Additional Information:||http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-17-010.html|
|Contact Information:||If you have difficulty accessing the full announcement electronically, please contact:
NIH OER Webmaster FBOWebmaster@OD.NIH.GOV