For this program project, we will establish a bioinformatics core to process and analyze the large amount of data that will be generated by its four projects. We propose a comparative study of genome maintenance and tumor suppression in relation to aging in rodents. While it has long been observed that rodents differ enormously in their life spans, the mechanisms behind this difference remain unclear. Lack of this information is an important problem, because, without this knowledge, acquiring the ability to modulate aging on the whole organism level is highly unlikely. Our long-term goal is to understand the mechanisms that determine longevity. The overall objective of the bioinformatics core is to provide computational support and service to the project investigators - namely, both to work with each project to handle data generated therein and to integrate data from all projects to achieve the aims of the program project grant as a whole. The central hvpothesis of this Program is that long-lived rodents have evolved specific molecular mechanisms that mediate their longevity. This hypothesis has been formulated on the basis of preliminary data produced in the applicants'laboratories. The rationale for a dedicated bioinformatics core is that a consolidated facility is needed to manage the large amount of data on the whole genome level generated by each of four highly integrated projects of this program project. This bioinformatics core will be established to achieve three specific aims: 1) To deveipp a Web portal to warehouse and share data generated by projects;2) To facilitate projects to process and analyze the data that they generate;3) To integrate project data at the systems level and identify genetic network related to life span control. The function of the bioinformatics core is significant, because it will be set up to meet the challenge posed by the high volume of data that need to be generated, examined at multiple levels by a variety of approaches, integrated to develop the models of lifespan control, and shared among project investigators.
; The proposed bioinformatics core is relevant to public health because the Web data portal and novel computational methods, which will be developed to tackle the genetic bases behind the enormous difference in life span among rodents, will also be used to disseminate the data to the larger research community. The proposed research is relevant to the Nll-l's mission in that it pertains to developing fundamental knowledge that will help reduce the burdens of human disability associated with advanced age.
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| Sziráki, András; Tyshkovskiy, Alexander; Gladyshev, Vadim N (2018) Global remodeling of the mouse DNA methylome during aging and in response to calorie restriction. Aging Cell 17:e12738 |
| Hébert, Jean M; Vijg, Jan (2018) Cell Replacement to Reverse Brain Aging: Challenges, Pitfalls, and Opportunities. Trends Neurosci 41:267-279 |
| Tan, Li; Ke, Zhonghe; Tombline, Gregory et al. (2017) Naked Mole Rat Cells Have a Stable Epigenome that Resists iPSC Reprogramming. Stem Cell Reports 9:1721-1734 |
| Nieborowska-Skorska, Margaret; Sullivan, Katherine; Dasgupta, Yashodhara et al. (2017) Gene expression and mutation-guided synthetic lethality eradicates proliferating and quiescent leukemia cells. J Clin Invest 127:2392-2406 |
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