Molecular, cellular, and physiological response to DNA damage, genotoxic stress, and cell death across living systems: RadSource RS-2000 X-ray irradiator

遗传毒性应激包括DNA损伤和生物体对这种损伤的复杂反应。它包括DNA修复、多种细胞信号传导和转录反应、细胞活力和增殖的下游变化以及涉及许多生理系统的全身效应。对遗传毒性应激的有效反应对于所有生命形式的急性DNA损伤的修复至关重要。在高等生物中，它也是干细胞维持和组织更新以及适应性免疫系统中程序性DNA损伤的解决所必需的。挑战，团队和设备：在各种系统中有效和可重复地诱导DNA损伤，遗传毒性应激和细胞死亡对于研究这些基本生物过程以及自然科学和工程（NSE）的许多其他研究领域至关重要。我们的申请汇集了一个由12名申请人和16名设备用户组成的多学科团队，并要求购买一台RS-2000 X射线辐照器，以取代今年早些时候发生故障并被评估为无法修复的仪器。I.缺乏所需的设备是许多杰出的NSE研究人员持续取得成功和生产力的主要障碍，诱导遗传毒性应激的替代策略构成了重大的实验，后勤，财务和监管挑战。申请的辐照器满足了这一需求，并满足以下所有技术要求：（a）剂量精度、均匀性、再现性和组织穿透性，（B）细胞和小动物模型应用，以及（c）安全性和无放射性物质。二.优点、影响和可行性该应用程序由来自麦吉尔大学的大量NSE研究人员组成的团队提供支持，领导NSERC的科学发现和创新使命;所需的设备对于支持他们的研究至关重要。鉴于团队的规模和他们对设备的广泛专业知识，新仪器将有很高的需求，并立即广泛使用。制定了设备操作、培训和财务管理的详细计划。三. HQP培训申请人在HQP培训方面有着良好的记录，他们的学员将在许多正在进行的实验中使用所要求的设备。因此，所要求的设备对于HQP的成功至关重要，并将促进获得新的技术技能，提高研究生产力，增加研究成果的影响和创新，并促进HQP在学术界和工业界的职业发展。EDI的原则与HQP的培训计划紧密结合。总结：所要求的设备对于支持许多优秀的NSERC资助的研究计划至关重要，将带来NSE知识创造和技术创新的重大进步，并将大大提高麦吉尔大学NSERC研究社区的HQP培训质量。

Introduction: Genotoxic stress comprises DNA damage and the complex responses of an organism to such damage. It includes DNA repair, diverse cellular signaling and transcriptional responses, downstream changes in cell viability and proliferation, and systemic effects involving many physiological systems. Efficient response to genotoxic stress is essential across all life-forms for the repair of acute DNA damage. In higher organisms it is also required for stem cell maintenance and tissue renewal, and for the resolution of programmed DNA damage in the adaptive immune system. Challenge, Team, & Equipment: Effective and reproducible induction of DNA damage, genotoxic stress, and cell death in various systems is essential to study such fundamental biological processes and for many other lines of research in natural sciences and engineering (NSE). Our application brings together a multidisciplinary team of 12 applicants and 16 equipment users, and requests to purchase an RS-2000 X-ray irradiator, to replace an instrument that broke down earlier this year and is assessed beyond repair. I. Urgency & Suitability Lack of the requested equipment is a major hindrance for the ongoing success and productivity of many outstanding NSE researchers, and alternative strategies for the induction of genotoxic stress pose major experimental, logistical, financial, and regulatory challenges. The requested irradiator addresses this need and satisfies all the technical requirements for (a) dose precision, uniformity, reproducibility, and tissue penetration, (b) applications for cells and small animal models, and (c) safety and lack of radioactive material. II. Merit, Impact, & Feasibility The application is supported by a large team of NSE researchers from across McGill University, leading in the NSERC mission of scientific discovery and innovation; and the requested equipment is essential to support their research. Given the team size and their vast expertise with the equipment, the new instrument will be in high demand, and used immediately and widely. Detailed plans for equipment operation, training, and financial management are established. III. HQP Training The applicants have an excellent track-record in HQP training, and their trainees will use the requested equipment hands-on in many of their ongoing experiments. The requested equipment is therefore essential for HQP success and will promote the acquisition of new technical skills, enhance research productivity, increase the impact and innovation of the research outputs, and promote HQP career advances in academia and industry. The principles of EDI are tightly integrated into the HQP training program. Summary: The requested equipment is essential to support many outstanding NSERC-funded research initiatives, will bring major advances in NSE knowledge creation and technological innovation, and will greatly improve the quality of HQP training in the NSERC research community of McGill University.