Transcription initiation: molecular mechanisms of TFE

决定生物体基本布局、发育和行为的信息大多包含在它们的基因中。这种遗传信息的检索被称为转录，并由RNA聚合酶(RNAP)促进。为了及时获得正确的信息，这种酶与额外的蛋白质(转录因子)相互作用。在某些情况下，转录因子发生故障是因为它们被改变(突变)/导致在错误的时间读取和应用错误的信息，从而导致疾病。我们需要了解这些因素是如何与酶相互作用的，以便了解这些疾病的原因，并最终如何治疗它们。我的研究建议集中在转录因子之一TFE上。我们对TFE在转录过程中实现了什么有合理的了解，但我们不知道它是如何实现的。从本质上讲，我们并不了解TFE功能的潜在机制。我们提出的项目将通过在表征转录的实验设置中测试该因子和RNAP的突变变体的组合来解决这些问题。我们将使用生物物理技术来研究由于TFE的影响RNAP的结构是如何变化的。综上所述，该研究方案主要集中在基础TFE因子和RNA聚合酶的结构和功能上。

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.