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

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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.