TRIREME Mission |
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| The overarching goal of the TRIREME project is to develop and implement a multi-disciplinary strategy for obtaining a systems-level, multi-layer understanding of a major cornerstone of cellular homeostasis – the DNA damage response (DDR). The DDR is responsible for the stability and integrity of the genome. Genetic defects in critical relays of the network lead to genomic instability syndromes, which are almost invariably characterized by degeneration of specific tissues, signs of premature aging, sensitivity to specific DNA-damaging agents, and a marked predisposition to cancer. In addition, many of the cancer treatment regimens are based on DNA damaging agents. Systems-level understanding of the signaling networks induced by DNA damage is of great importance for human health: it will enhance our knowledge of physiological processes that lead to malignant transformation, aging and tissue degeneration on the one hand, and will point to novel approaches to enhancing the efficacy of cancer therapeutic agents on the other.
The TRIREME project brings together a multi-disciplinary consortium of six research groups with long-standing expertise in the fields of DNA damage responses, cell cycle control, functional genomics, proteomics and computational biology. The TRIREME project focuses on one prototypic DNA damage inducing agent – ionizing radiation (IR), which is the agent used in cancer radiotherapy. The most cytotoxic DNA lesion induced by IR is the double strand break (DSB), a lesion that vigorously mobilizes the DDR. The cellular network activated by IR will be systematically analyzed on all its major layers – the transcriptome, microRNAome, proteome, and key post-translational modifications (phosphorylations, ubiquitylations and SUMOylations) – together with genome-wide functional screens aimed at identifying new players in the DDR. Novel computational algorithms will be developed to glean information from these heterogeneous data sources, algorithms that will construct systems-level, multi-layer, predictive models of the cellular networks induced by IR. |
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