The Wbl proteins - a novel family of [4Fe-4S] cluster-containing transcription factors

被称为链霉菌的无害土壤细菌对我们的福利很重要，因为它们是用于治疗传染病的绝大多数抗生素的来源，也为我们提供了许多其他药物，例如用于治疗癌症和帮助器官移植患者。我们已经确定了两个关键的调节因子（称为“转录因子”），它们可以转换这些有用细菌的遗传机制，使它们能够自我繁殖。我们发现，这些调节器是不寻常的，包含一个特殊的传感装置（称为“铁硫簇”），它可能控制细菌的繁殖，以响应关键的环境信号，如氧气。在这项资助中，我们希望确切地了解这些调节器是如何工作的，了解它们在细胞中的作用以及特殊传感装置（“铁硫簇”）的作用。我们还知道，类似的关键调节因子存在于导致肺结核和白喉等重要致命疾病的危险细菌中。在导致结核病的细菌中，这些调节因子之一控制着对多种抗生素的耐药性（一种称为“多药耐药性”的现象）。如果我们能够理解这些调节器是如何工作的，我们就能够开发出针对和消除多药耐药性的新药，从而使治愈结核病患者变得更加容易。

The harmless soil bacteria called streptomycetes are important to our welfare because they are the source of the vast majority of antibiotics used to cure infectious diseases, as well as providing us with numerous other medicines used, for example, to treat cancer, and to help organ transplant patients. We have identified two key regulators (called 'transcription factors') that switch the genetic machinery of these useful bacteria to allow them to reproduce themselves. We have discovered that these regulators are unusual in containing a special sensing device (called an 'iron-sulphur cluster') which likely controls reproduction of the bacteria in response to key environmental signals, like oxygen. In this grant we expect to find out exactly how these regulators work, to understand what they do in the cell and the role of the special sensing device (the 'iron-sulphur cluster'). We also know that similar key regulators are present in dangerous bacteria that cause important fatal diseases like tuberculosis and diphtheria. In the bacterium that causes tuberculosis, one of these regulators controls resistance to a wide range of antibiotics (a phenomenon called 'multi-drug resistance'). If we can understand how these regulators worked, we may be able to develop new medicines to target and eliminate multi-drug resistance, making it much easier to cure patients suffering from tuberculosis.