X-Ray Irradiation Platform for cells and small animal studies

用于细胞和小动物研究的 X 射线照射平台

基本信息

  • 批准号:
    RTI-2017-00336
  • 负责人:
  • 金额:
    $ 10.9万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Research Tools and Instruments
  • 财政年份:
    2016
  • 资助国家:
    加拿大
  • 起止时间:
    2016-01-01 至 2017-12-31
  • 项目状态:
    已结题

项目摘要

This application is to request funding for the purchase of an X-Ray irradiator that allows whole body irradiation of small animals as well as ex vivo cell culture models. The Lady Davis Institute (LDI) has witnessed a massive surge in users requiring ionizing irradiation for their studies. Ionizing radiation is a powerful tool that is utilized in the fields of immunology, DNA damage/repair and telomere biology. Whole body irradiation is a standard procedure in immunology to produce bone marrow ablation in small animals, which allows the subsequent transplantation of donor hematopoietic stem cells. Ex vivo X-ray irradiation is also commonly used to evaluate the potential of cells to repair DNA breaks and maintain telomere structure. Up to now, researchers at the LDI have used the hospital’s clinical irradiator. This has been problematic for basic researchers as it is only available when clinicians are done treating patients. With the increased demand for radiation therapy, the access to the irradiator for basic researchers has become more and more difficult and worsen. Moreover, while researchers can reserve time to use it, appointments are frequently canceled to prioritize patient care. Furthermore, researchers are unable to operate the irradiator themselves and rely on coordinating with the technician to perform the actual procedures. This ongoing situation has prevented critical experiments to be performed and significantly decreased the productivity of a number of fundamental research programs, including those of the principal applicant Dr. Alexandre Orthwein and his co-applicants Drs. Koren Mann and Chantal Autexier. Acquiring an ‘in house’ irradiator is therefore essential for multiple LDI research labs to reach their full potential. These include 9 additional researchers at the Lady Davis Institute, for whom ex vivo or in vivo studies to understand DNA repair mechanisms in different cellular contexts. This equipment will complement the existing infrastructure and core facilities already offered at the LDI. It will be installed in the small animal Research Core facility to promote maximal usage. This will allow whole body irradiation to be performed with mouse or rat animal cages, irradiation to targeted areas with the use of a fixed collimator, or irradiation on cells. The X-ray cabinet provides a large area with space for up to 12 small animals or multiple samples to be irradiated, and is self-shielded, thereby requiring no additional barrier or infrastructure renovation. Once integrated into the LDI, this equipment will serve to: (i) accelerate multiple research programs, (ii) allow for training of high quality personnel (i.e. students and post-doctoral fellows), and (iii) produce quantitative data that will allow researchers to increase the impact of their projects. It will also be critical to enhance collaborations between different research units at the LDI.
该申请旨在申请资金,用于购买一台X射线辐照器,该辐照器可对小动物进行全身辐照,并可进行离体细胞培养模型。戴维斯夫人研究所(LDI)见证了需要电离辐射进行研究的用户的大量激增。电离辐射是免疫学、DNA损伤/修复和端粒生物学领域中使用的有力工具。全身照射是免疫学中的标准程序,用于在小动物中产生骨髓消融,这允许随后移植供体造血干细胞。离体X射线照射也常用于评估细胞修复DNA断裂和维持端粒结构的潜力。到目前为止,LDI的研究人员已经使用了医院的临床辐照器。这对基础研究人员来说是个问题,因为只有当临床医生完成对患者的治疗时才能使用。随着放射治疗需求的增加,基础研究人员获得辐射器变得越来越困难和恶化。此外,虽然研究人员可以预留时间使用它,但预约经常被取消,以优先考虑患者护理。此外,研究人员无法自己操作辐照器,而是依赖于与技术人员协调来执行实际程序。这种持续的情况阻碍了关键实验的进行,并显著降低了许多基础研究项目的生产力,包括主要申请人Alexandre Orthwein博士及其共同申请人Koren Mann博士和Chantal Autexier博士的项目。因此,获得“内部”辐照器对于多个LDI研究实验室充分发挥其潜力至关重要。其中包括戴维斯夫人研究所的另外9名研究人员,他们进行了体外或体内研究,以了解不同细胞环境中的DNA修复机制。 这些设备将补充LDI已经提供的现有基础设施和核心设施。它将被安装在小动物研究中心设施,以促进最大的使用。这将允许使用小鼠或大鼠动物笼进行全身照射,使用固定准直器对靶区域进行照射,或对细胞进行照射。X射线柜为多达12只小动物或多个样品提供了大面积的空间进行辐照,并且是自屏蔽的,因此不需要额外的屏障或基础设施改造。 一旦集成到LDI中,该设备将用于:(i)加速多个研究项目,(ii)允许培训高质量的人员(即学生和博士后研究员),以及(iii)产生定量数据,使研究人员能够增加其项目的影响。加强地方发展研究所不同研究单位之间的合作也至关重要。

项目成果

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Orthwein, Alexandre其他文献

Mitosis Inhibits DNA Double-Strand Break Repair to Guard Against Telomere Fusions
  • DOI:
    10.1126/science.1248024
  • 发表时间:
    2014-04-11
  • 期刊:
  • 影响因子:
    56.9
  • 作者:
    Orthwein, Alexandre;Fradet-Turcotte, Amelie;Durocher, Daniel
  • 通讯作者:
    Durocher, Daniel
A Cell Cycle-Dependent Regulatory Circuit Composed of 53BP1-RIF1 and BRCA1-CtIP Controls DNA Repair Pathway Choice
由 53BP1-RIF1 和 BRCA1-CtIP 组成的细胞周期依赖性调节回路控制 DNA 修复途径的选择。
  • DOI:
    10.1016/j.molcel.2013.01.001
  • 发表时间:
    2013-03-07
  • 期刊:
  • 影响因子:
    16
  • 作者:
    Escribano-Diaz, Cristina;Orthwein, Alexandre;Durocher, Daniel
  • 通讯作者:
    Durocher, Daniel
MAD2L2 controls DNA repair at telomeres and DNA breaks by inhibiting 5' end resection.
MAD2L2通过抑制5'末端切除来控制端粒的DNA修复和DNA断裂。
  • DOI:
    10.1038/nature14216
  • 发表时间:
    2015-05-28
  • 期刊:
  • 影响因子:
    64.8
  • 作者:
    Boersma, Vera;Moatti, Nathalie;Segura-Bayona, Sandra;Peuscher, Marieke H.;van der Torre, Jaco;Wevers, Brigitte A.;Orthwein, Alexandre;Durocher, Daniel;Jacobs, Jacqueline J. L.
  • 通讯作者:
    Jacobs, Jacqueline J. L.
Active nuclear import and cytoplasmic retention of activation-induced deaminase
  • DOI:
    10.1038/nsmb.1598
  • 发表时间:
    2009-05-01
  • 期刊:
  • 影响因子:
    16.8
  • 作者:
    Patenaude, Anne-Marie;Orthwein, Alexandre;Di Noia, Javier M.
  • 通讯作者:
    Di Noia, Javier M.
In vivo genome-wide CRISPR screening in murine acute myeloid leukemia uncovers microenvironmental dependencies.
  • DOI:
    10.1182/bloodadvances.2022007250
  • 发表时间:
    2022-09-13
  • 期刊:
  • 影响因子:
    7.5
  • 作者:
    Mercier, Francois E.;Shi, Jiantao;Sykes, David B.;Oki, Toshihiko;Jankovic, Maja;Man, Cheuk Him;Kfoury, Youmna S.;Miller, Elizabeth;He, Shutao;Zhu, Alexander;Vasic, Radovan;Doench, John;Orthwein, Alexandre;Michor, Franziska;Scadden, David T.
  • 通讯作者:
    Scadden, David T.

Orthwein, Alexandre的其他文献

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