Assembly and function of DNA double-strand break repair foci.

我已建立的研究项目因使用创新的、多学科的方法来识别调节细胞对DNA损伤的反应的分子和细胞机制而脱颖而出。这个项目的中心是细胞生物学中的一个基本问题，即不同的DNA修复途径是如何调节和激活的，以应对大量不同的DNA损伤事件。针对不同类型的DNA损伤，有特定的分子传感器，然后将特定的反应传递给下游的分子复合体，导致细胞周期检查点激活和DNA修复途径的处理。这项拟议的工作旨在开发和使用不同的互补技术来识别、量化和表征参与调节DNA修复机制的蛋白质的相互作用网络。我们将进一步扩展我们的生化纯化和基于质谱学的分析，以产生新的方法，并改进我们过去开发的方法。这些方法将使我们能够识别被招募到DNA损伤部位的蛋白质，并确定它们在这些重要过程中的功能。重要的是，我们的方法允许我们绕过传统生化技术的限制，这对于完整描述调控DNA修复机制的不同成分是必不可少的。因此，从拟议研究中获得的技术专门知识将为我们提供可在我们的项目中使用的工具和专门知识，并为科学界的其他成员服务。蛋白质组学研究领域展示了新的和创新的发现的强大潜力，也是学术和工业研究实验室中非常受欢迎的专业知识。因此，这项研究计划非常适合希望获得这一独特专业知识的学生和个人。

My established research program stand out for using innovative, multi-disciplinary approaches to identify the molecular and cellular mechanisms that regulate the cellular response to DNA damage. This project centers on a fundamental question in cell biology, namely how are the different DNA repair pathways regulated and activated in response to a multitude of different DNA damaging events. There are specific molecular sensors for the different types of DNA damage, which then relay a specific response to downstream molecular complexes, resulting in cell cycle checkpoint activation and DNA repair pathway processing. The proposed work aims to develop and use different complimentary techniques that identify, quantify and characterize interaction networks of proteins involved in regulating DNA repair mechanisms. We will further extend our biochemical purification and mass spectrometry based assays to generate novel approaches, as well as improve on methods we have developed in the past. These methods will allow us to identify proteins that are recruited to sites of DNA damage, and determine their function in these important processes. Importantly, our approaches allow us to circumvent limitations of conventional biochemical techniques, which is essential for a complete characterization of the different component regulating DNA repair mechanisms. Thus, the technical expertise gained from the proposed studies will provide us with tools and expertise that can be use in our projects, as well as serve the rest of the scientific community. The field of proteomic research presents strong potential for novel and innovative discoveries, and is also a very sought after expertise in both academic and industry research laboratories. As such, this research program is perfectly fitted for students and personals willing to gain this unique expertise.