Immunogenetics of antibody affinity

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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.**