Alliance for Lupus Research: Functional Genomics and Molecular Genetic Pathways in SLE

Applications should focus on 2 principal areas: [1] functional validation to determine which candidate genes/variants identified in human lupus have an authentic role in the disease and [2] detailed elucidation of the molecular pathways modulated by these candidate genes/variants identified in human lupus. All proposals submitted must be based on information in the public domain. Responsive applications will propose research to elucidate the functional implications of the genetic variants identified in human lupus studies. Lupus-associated genes studied in animal models that are not among those also identified in human studies are not appropriate topics for this grant mechanism. ALR will focus support on:
·Human Studies: Functional validation studies could use human DNA samples from phenotypically well-characterized individuals to correlate a gene variant with a particular phenotype. Such human studies are particularly encouraged.
·Genetic Models: Established genetic models as well as emerging genetic models can be used to look at in vivo gene/variant function.
·RNA interference: RNAi depletion of candidate genes in cells, tissues or whole organisms can be used to identify phenotypes.
·Imaging strategies: Imaging of cell trafficking in vivo might be useful in characterizing the impact of lupus-associated gene variants on immune responses or inflammation.
·Systems-level approaches: Bioinformatic resources can be mined to generate testable hypotheses concerning the function of candidate genes and groups of genes.
·Cellular or circuit-level approaches: Studies might compare gene/variant functional consequences at the cellular and circuit levels, especially with respect to a drug challenge.
·Epigenetics: Functional validations of epigenetic mechanisms of gene regulation in the context of lupus, including potential maternal and paternal imprinting or X chromosome inactivation.
·Comparison of wild type and gene variant functions: Molecular alteration associated with a gene variant frequently does not reveal whether the function of a particular gene is increased, decreased, or leads to unexpected functional consequences. Approaches using in vivo transgenes, in vitro biochemical assays, or other validation methods that can address these issues will help to identify the most promising molecular targets for therapeutic interventions.
·Identification of functionally significant sequences in disease-associated genomic regions: While some genomic regions show strong statistical association with a diagnosis of SLE, in many cases the specific sequences responsible for the association have not yet been identified. Deep sequencing approaches can be used to define the specific regulatory or coding sequences responsible for the association with SLE and their impact on cell function.
Funding: Research Grants: Up to $350K over 2 years. Pilot Grants: up to $75K for one year.
http://www.lupusresearch.org/research/grants.html