Transcription initiation: molecular mechanisms of TFE

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The information that determines the basic layout, development and behaviour of living organisms is mostly contained within their genes. The retrieval of this genetic information is termed transcription and is facilitated by the enzyme RNA Polymerase (RNAP). In order to access the right information in a timely manner this enzyme interacts with additional proteins (transcription factors). In some cases transcription factors are malfunctioning because they are altered (mutated) / resulting in the wrong information being read and applied at the wrong time and this causes diseases. We need to understand how the factors interact with the enzyme in order to understand the cause of such diseases and ultimately how to treat them. My research proposal focuses on one of the transcription factors, TFE. We have a reasonable knowledge of what TFE achieves during transcription but we do not know how. In essence, we do not understand the mechanisms underlying TFE function. The project we are proposing will address these questions by testing combinations of mutant variants of this factor and RNAP in experimental setups that characterise transcription. We will use biophysical techniques to examine how the structure of RNAP changes due to the influence of TFE. In summary, the research proposal is focused on the structure and function of the basal TFE factor and the RNA Polymerase enzyme.