Molecular recognition in post-transcriptional regulation 2

人体和复杂生物体的功能一般需要在不同类型的细胞中产生不同的蛋白质。这种特定于细胞类型的蛋白质生产是通过精确调控遗传密码到蛋白质的翻译来实现的。这一翻译过程中的两个步骤是，首先将DNA编码的信息翻译成RNA，然后将RNA编码翻译成蛋白质分子。这两个过程都受到生物机器的调控，生物机器由蛋白质组成，在某些情况下，还包括RNA分子。我们专注于RNA到蛋白质步骤(或转录后调节)的调节，并研究蛋白质RNA机器如何在溶液环境中组装和调节基因表达。我们的结构研究补充了其他技术，如X射线结晶学，可用于研究处于静态结晶状态的分子。分析控制蛋白质合成调控的分子结构具有直接的医学意义，因为这一过程是以常见的遗传病、癌症和病毒感染为基础的。我们研究一种重要的调节机制，称为ARE介导的mRNA衰退(AMD)，它在炎症和愈合过程中增加特定蛋白质的合成。这种机制，如果永久开启，可能会导致炎症性关节炎和癌症。我们想要了解开关在分子水平上的工作原理，并设计特定的治疗方法，以便在需要时关闭开关。||使用类似的技术方法，我们还在研究疱疹病毒的一种关键调节蛋白。该项目希望促进抗疱疹药物的设计，以治疗感染这种病毒的人，这种病毒对免疫功能低下的患者构成主要威胁，增加了器官移植和化疗的风险，并降低了艾滋病患者的预期寿命。例如，如果我们要设计或优化化合物以将蛋白质和RNA锁定在非功能构象中或(去)稳定蛋白质RNA复合体，就需要从分子上了解ICP27与其功能结合伙伴的相互作用。

The functioning of the human body and of complex organisms in general requires different proteins to be produced in different types of cells. This cell-type-specific protein production is achieved by precisely regulating the translation of the genetic code into proteins. The two steps in this process of translation are, first, the translation of the DNA-encoded information into RNA and, then, the translation of the RNA code into a protein molecule. Both processes are regulated by biological machines, which are composed of proteins and, in some cases, RNA molecules. We focus on the regulation of the RNA-to-protein step (or post-transcriptional regulation) and investigate how the protein RNA machines assemble in a solution environment and regulate gene expression. Our structural studies complement other techniques such as X-ray crystallography, which can be used to study molecules in a static crystalline state. Analysing the structures of the molecules that govern regulation of protein synthesis has a direct medical relevance, as this process lies at the basis of common genetic diseases, cancer and viral infections. We work on an important regulatory mechanism, called ARE mediated mRNA decay (AMD), that increase the synthesis of specific proteins in inflammation and healing processes. This mechanism, if permanently switched on, can lead to inflammatory arthritis and cancer. We want to understand how the switch works at the molecular level and design specific therapies to switch in off when required.||Using a similar technical approach we are also investigating a key regulatory protein from herpes virus. This project wants to facilitate the design of anti-herpes drugs to treat people infected with this virus, which forms a major threat to immunodepressed patients, increases the risk of organ transplantation and chemotherapy and reduces the life expectancy of AIDS sufferers. Molecular insight into the interaction of ICP27 with its functional binding partners needs to be obtained if we are, for example, to design or optimise compounds to lock protein and RNA in a non-functional conformation or to (de)stabilise protein RNA complexes.