Immunogenetics of antibody affinity

抗体亲和力的免疫遗传学

• 批准号: RGPIN-2019-05047
• 负责人: Lesage, Sylvie
• 金额: $ 3.06万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=760940
• 关键词: Immunogenetics; antibody; affinity

The overarching aim of our research program is to address how variations in the genetic code influence the immune system. To achieve this goal we use a variety of genetically different mouse models. Our previous work has resulted in the identification of new molecular pathways that determine the number of specific immune cells. While studying these cells, we serendipitously generated new mouse models that inefficiently produce antibodies. Our specific objective for the next five years is thus to exploit our newly developed mouse models to identify genes or molecular processes that regulate the production of high affinity antibodies. Antibodies are proteins that are produced by the immune system. In addition to protecting the host against pathogens, antibodies serve as useful tools in multiple facets of biological sciences. They specifically recognize various molecular structures with high affinity. Therefore, our goal is to better define the process leading to high affinity antibody production to improve the quality of the reagents used in the laboratory. One of our new mouse strain carries 21 mutated genes relative to the control mouse. In the first aim, we will target each of these genes, one by one, to identify the gene(s) that contribute to the generation of high affinity antibodies. In the second aim, we will perform an unbiased approach and determine the ability of more than 200 strains of mice at generating high affinity antibodies. By pairing the genetic information of these 200 strains with their ability or inability to produce high affinity antibodies, we will be able to identify new genes involved in affinity maturation. Altogether, our approach will identify new molecular pathways that influence the production of high affinity antibodies to facilitate the production of better antibody reagents. An integral aspect of this program is the nature and quality of personnel training. Indeed, this program requires both cross-disciplinary expertise and international collaborations. We will train at least two graduate students and five undergraduate students in the five-year funding time frame. All the students will acquire strong skillsets in a variety of research fields and techniques, including molecular biology, immunogenetics, mouse handling, cell culture, cellular immunology, and systems biology. The undergraduate students leading summer projects will present the results emanating from their work in various locals meetings. In addition to local meetings, the graduate students will have the opportunity to participate in both national and international meetings. As the 200 mouse strains are held in different facilities in the USA, Europe and Australia, the graduate student leading this aspect of the project will learn to lead an international collaborative project. Altogether, this program will facilitate the training of highly qualified personnel, opening the door to a variety of job opportunities in both the private and public sectors.

我们研究计划的首要目标是解决遗传密码的变化如何影响免疫系统。为了实现这一目标，我们使用了多种遗传上不同的小鼠模型。我们以前的工作已经确定了决定特定免疫细胞数量的新分子途径。在研究这些细胞时，我们偶然产生了新的小鼠模型，这些小鼠模型不能有效地产生抗体。因此，我们未来五年的具体目标是利用我们新开发的小鼠模型来鉴定调节高亲和力抗体产生的基因或分子过程。抗体是由免疫系统产生的蛋白质。除了保护宿主免受病原体侵害外，抗体还在生物科学的多个方面充当有用的工具。它们以高亲和力特异性识别各种分子结构。因此，我们的目标是更好地定义导致高亲和力抗体产生的过程，以提高实验室中使用的试剂的质量。我们的一个新品系小鼠携带21个相对于对照小鼠的突变基因。在第一个目标中，我们将逐一靶向这些基因中的每一个，以鉴定有助于产生高亲和力抗体的基因。在第二个目标中，我们将执行无偏的方法，并确定200多种小鼠产生高亲和力抗体的能力。通过将这200个菌株的遗传信息与它们产生高亲和力抗体的能力或能力进行配对，我们将能够识别参与亲和力成熟的新基因。总之，我们的方法将确定影响高亲和力抗体产生的新分子途径，以促进更好的抗体试剂的生产。 该计划的一个组成部分是人员培训的性质和质量。事实上，该计划需要跨学科的专业知识和国际合作。我们将在五年的资助时间内培养至少两名研究生和五名本科生。所有学生将获得各种研究领域和技术的强大技能，包括分子生物学，免疫遗传学，小鼠处理，细胞培养，细胞免疫学和系统生物学。领导暑期项目的本科生将在各种当地会议上展示他们的工作成果。除了本地会议，研究生将有机会参加国家和国际会议。由于200种小鼠品系在美国，欧洲和澳大利亚的不同设施中进行，因此领导该项目的研究生将学习领导国际合作项目。总之，该方案将促进高素质人才的培训，为私营和公共部门的各种就业机会打开大门。