Eric Ortlund, Graeme Conn
An important unanswered question in biology is how proteins evolved to recognize other proteins, small molecules, DNA and RNA. These interactions, which drive intricate cell signaling networks, rely on biomolecules that often perform multiple functions. Emory University researchers propose to use a methodology known as ancestral gene resurrection to understand the mechanisms by which these biomolecules evolved their current functions. Ancestral gene resurrection is the process of using information from the evolutionary tree to reconstruct ancient genes which can then be used to generate the RNAs and proteins they encode. The investigators will derive ancient transcription factors and noncoding RNAs and determine the evolutionary steps that enabled them to acquire their unique functions. They will use the ancient molecules as tools to discover the forces that shaped the specific molecular interactions driving gene expression. A number of state-of-the-art cellular and biophysical methods will be applied to understand how DNA sequence changes drove changes in cell signaling. Their findings may help researchers generate predictive knowledge regarding how DNA sequence drives gene regulation, enabling the generation of algorithms designed to predict the functional outcome of transcription factor binding. Moreover, the work will likely have significant impact on understanding the biophysical principles underlying the structure-function relationships in protein-DNA and protein-RNA complexes.
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