Next Generation Genetic Association Studies (U01)

archived

Purpose. This FOA issued by the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, encourages applications from institutions or organizations that propose to utilize cellular reprogramming, molecular profiling, and genomics to investigate functional aspects of genetic variation in humans. NHLBI is soliciting a phased technology development and implementation program whose goal is to add a functional dimension to genomic studies by combining cellular reprogramming strategies with molecular profiling or cellular assays, followed by integration of this information with existing genotypic and clinical phenotypic data to assess how naturally occurring human genetic variation influences the activities of biological networks in cell-based models of disease. Since the design and conduct of such studies will require several areas of expertise, applicants are encouraged to include multiple PIs on the application. Mechanism of Support. This FOA will utilize the U01 (cooperative agreement) grant mechanism. Applicants will submit a single application organized into three phases, beginning with Phase I which will have technology development to generate induced pluripotent stem (iPS) cells from human samples and differentiate these iPS cells into tissues relevant to heart, lung, blood and sleep (HLBS) diseases. Phase II involves ramping up the technology developed in Phase I for high throughput generation of differentiated cells from iPS cells in population samples. Phase III will utilize technology developed in Phases I and II to test genome wide association study (GWAS) generated functional hypotheses in cell-based models of disease. Applicants may propose Phases I to III or II to III depending on the current state of iPS generation and cell type differentiation technology needed to meet their specific aims. Inclusion of Phase I is dependent on the validation and reproducibility of cell differentiation protocols for the specific cell type(s) proposed in the application.

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