The Bioinformatics Core (Core B) will provide computational support to all projects and cores to transform their data into predictive models and integrate their diverse experimental approaches to understanding age- related protein detoxification. In particular, it will integrate mRNA and protein expression profiling in C. elegans, mouse and cell culture models with comparative genomics of promoter sequences to build a transcriptional model of this process in these diverse phyla, and provide candidate effector proteins for biochemical and genetic analysis. This will integrate and extend these transcriptional and protein networks to vertebrate and other model systems, using comparative genomics, database mining and experimental analysis performed by our colleagues. We will correlate our data with extensive and growing public databases and literature knowledge on protein function, pathways and interactions, to bridge large gene lists to discrete functions and logic. Finally, we will provide a range of computational supports for each individual project (programming, database generation and data mining), and in integrating their results into a robust, and conserved models of the protein detoxification machinery that can be shared throughout the project and ultimately with the broader community. Public Health Relevance This project will uncover themechanisms bywhich diverse organisms - andultimately humans - detoxify protein aggregates formed during aging, leading to better diagnosis and potentially effective treatments for a range of aging related diseases such as Alzheimer's and Parkinson's disease. This bioinformatics core will assist in many ways, in particular to build a detailed model for this process, and to translate these mechanisms from worms to mouse to human, assisting both our overall understanding of the process, and the potential for therapeutic application. With a particular focus on enhancing the value of large data sets, this core will also provide the community with a valuable knowledge base to assist other investigations in this field.
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