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Most of the current understanding of regulation of biological systems is based on the single stimulus-single gene response paradigm. However, in real life systems, each gene is subject to a multiplicity of stimuli, which is integrated at the molecular level to generate a binary response. The binary response is further integrated at the level of population of molecules to give a graded response. We are therefore trying to address the much-overlooked question of biological signal integration at the single gene level, which is a fundamental question in biological regulation, using control of translation in inflammation and cancer as a model system. Understanding the transition from chronic inflammation to cancer is of major biomedical importance and the chronic inflammatory condition provides a complex cellular microenvironment where genes are exposed to multiple internal and external signals. Using both computational and experimental approaches we are elucidating the role of small regulatory RNAs, called microRNAs, and RNA-
binding proteins, in the translation regulation of these genes, and deciphering their molecular crosstalk which integrates different biological stimuli at the level of gene expression, and fine-tunes the inflammatory response. |