An x-ray irradiator cabinet for live cell irradiation

每一个生物体的细胞都在不断地暴露于DNA损伤，无论是通过内源性代谢的副产物产生的，还是由细胞外来源如辐射或化学物质产生的。虽然DNA损伤是常见的，但它可能导致突变，对细胞，组织和整个生物体产生负面影响。DNA损伤修复失败导致多种疾病，包括免疫缺陷、衰老、癌症和神经退行性疾病。因此，了解细胞如何对DNA损伤做出反应是理解细胞和物种长期和短期生存所必需的基本机制的关键。 这笔赠款提供的资金将允许购买一个Faxitron CellRad内阁X射线单位，提供一系列的辐射剂量的细胞和组织培养照射。细胞辐射导致细胞遗传物质（DNA）的损伤。这是一个实验模型系统，用于研究哺乳动物和人类细胞修复受损DNA的机制。该设备对于执行由NSERC资助的Schild-Poulter实验室研究计划至关重要，该计划旨在研究DNA修复蛋白Ku的作用，该蛋白对于哺乳动物细胞中DNA双链断裂的修复至关重要。虽然Ku对DNA的正常修复至关重要，但其作用方式仍不清楚。已知Ku与许多在DNA修复中发挥作用的其他因子相互作用，然而，这些相互作用的细节和结果知之甚少。使用Ku的晶体结构，可以预测蛋白质中可以接触其他蛋白质的区域。因此，在这些可接近区域中的几个中产生突变，以测试它们如何改变Ku DNA修复功能。已经确定了两个Ku突变，它们改变了其响应DNA损伤的功能。这些突变导致不同的缺陷，表明突变区域参与不同的功能。Schild-Poulter实验室目前正在努力鉴定与这些Ku基序相互作用的蛋白质，以阐明它们如何在DNA修复中共同发挥作用。 所要求的设备将提供在我们的细胞模型中诱导DNA损伤的方法，以便我们能够阐明Ku在DNA修复中的调节机制。 西方大学的其他几个实验室也需要这种设备，用于干细胞再生和细胞介导的免疫反应的研究。因此，由该设备产生的DNA损伤是一种工具，使学生，科学家和技术人员在其个人实验室或研究计划中的生物研究中使用的生物系统和实验成为可能。

The cells of every living organism are constantly being exposed to DNA damage, whether created through by-products of the endogenous metabolism, or generated by extracellular sources such as radiation or chemicals. While DNA damage is commonly encountered, it can cause mutations that have negative impacts on cells, tissues, and organisms as a whole. Failure to repair DNA lesions results in a multitude of conditions including immunodeficiency, aging, cancer, and neurodegenerative disorders. Thus, understanding how cells respond to DNA damage is key to comprehend fundamental mechanisms that are essential to long- and short-term survival of cells and species. The funding provided by this grant will allow the purchase a Faxitron CellRad cabinet X-ray unit that delivers a range of radiation doses for cell and tissue culture irradiation. Cell irradiation causes damage in the genetic material (DNA) of the cells. This serves as an experimental model system to study the mechanisms set in place by mammalian and human cells to repair their damaged DNA. This equipment is essential to carry out the Schild-Poulter lab’s research program funded by NSERC that investigates the role of the DNA repair protein Ku which is essential for the repair of DNA double-stranded breaks in mammalian cells. While it is understood that Ku is essential for the proper repair of DNA, its mode of action is still unclear. It is known that Ku interacts with a number of other factors that play roles in the repair of DNA, however, the details and the outcome of these interactions are poorly understood. Using the crystal structure of Ku, one can predict regions of the protein that are accessible to contact other proteins. Thus, mutations were generated in several of these accessible regions to test how they alter Ku DNA repair functions. Two Ku mutations that alter its ability to function in response to DNA damage have been identified. These mutations result in different defects suggesting that the mutated regions are involved in distinct functions. The Schild-Poulter laboratory is currently working to identify the proteins that interact with these Ku motifs to elucidate how they function together in the repair of DNA. The requested equipment will provide the means to induce DNA damage in our cellular models so that we can elucidate the regulatory mechanisms that underlie Ku function in DNA repair. This equipment is also needed by several other laboratories at Western University for research on stem cell regeneration and cell-mediated immune responses. Thus, the DNA damage created by this equipment is a tool to enable biological systems and experimentations used in biological research by students, scientists and technicians in their individual lab or research program.