Nuclear architecture: structure, function and disease

最近，科学家们开发了一些工具，用于识别患有复杂神经发育障碍的个体的突变。令人惊讶的是，这些突变中的许多都是在与细胞基本功能有关的蛋白质中发现的。为了了解这些疾病的分子基础，希望开发新的预后标记物和潜在的疾病治疗方法，了解特定蛋白在复杂的细胞环境中如何发挥作用至关重要。我的团队是分析DNA如何包装在人类细胞内称为细胞核的部分的专家，我们假设，在一些人中，他们的疾病是由DNA包装改变引起的，因此它不能正常工作。然而，这个过程有很多步骤，从包装DNA到如何读取DNA来制造RNA，然后RNA如何折叠并输出到细胞的其他部分来制造蛋白质。在这项研究中，我们将重点关注一种特定的蛋白质，HNRNPU，当它突变时会导致学习困难、自闭症和癫痫。到目前为止，我们的研究表明，HNRNPU与细胞核中另一种名为RNA的分子相互作用，共同形成一种包围DNA的凝胶，类似于保护性的棉花。这种凝胶共同促进了DNA上发生的过程，如读取RNA，或修复DNA损伤。我们将研究HNRNPU中的突变如何改变DNA包装，以及这如何影响许多重要的细胞过程和疾病。

Recently scientists have developed tools for identifying mutations in individuals with complex neuro-development disorders. Surprisingly, many of these mutations are found in proteins that have a role in fundamental cellular functions. To understand the molecular basis of these diseases, with a hope of developing new prognostic markers and potential disease treatments, it is crucial to understand how the specific proteins function in the complex environment of the cell. My team is expert in analysing how DNA is packaged inside part of a human cell called the nucleus and we hypothesise that in some individuals their disease is caused by altered packaging of DNA so it does not function correctly. However, there are many steps to this process from packaging DNA to how the DNA is read to make RNA and then how the RNA is folded and exported to other parts of the cell to make protein. In this study we will focus on one specific protein, HNRNPU, that when mutated causes learning difficulties, autism, and epilepsy. So far, our research has shown that HNRNPU interacts with another molecule in the nucleus called RNA and together they form a gel that surrounds the DNA, similar to protective cotton wool. Together this gel facilitates processes that occur on the DNA such as reading into RNA, or repairing damage to the DNA. We will study how mutations in HNRNPU alter DNA packaging and how this affects many important cellular processes and disease.