BCL10-MALT1 protein-protein interaction in lymphocyte function and dysfunction

BCL10-MALT1 蛋白-蛋白相互作用在淋巴细胞功能和功能障碍中的作用

基本信息

批准号：
10722751
负责人：
Lisa M Maurer
金额：
$ 17.32万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-12 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10722751
关键词：
Achievement Affect Animal Model Antigen Receptors Antigens Authorship Autoimmune Award B-Lymphocytes BCL10 gene Biochemistry Bioinformatics Biometry Cells Colitis Complex Development Plans Disease Disease model Educational Status Educational workshop Environment Event Experimental Designs Functional disorder Goals Grant Growth Immune Immune System Diseases Immunoglobulin Domain Immunology In Vitro Inflammation Inflammatory K-Series Research Career Programs Knowledge Laboratories Lymphocyte Lymphocyte Activation Lymphocyte Biology Lymphocyte Function Lymphocyte Subset Lymphoma Malignant - descriptor Malignant Neoplasms Manuscripts Mentors Mentorship Molecular Mucosa- associated lymphoid tissue lymphoma translocation protein-1 Mus Organ Pathogenesis Pathology Patient-Focused Outcomes Peptide Hydrolases Phenotype Physicians Play Positioning Attribute Preparation Production Productivity Proliferating Protease Inhibitor Protein Biochemistry Proteomics Psoriasis Records Regulatory T-Lymphocyte Research Role Scientist Seminal Signal Transduction Signaling Protein T-Lymphocyte T-Lymphocyte Subsets Technical Expertise Techniques Therapeutic Training Transcriptional Activation Universities Work Xenograft procedure biomedical scientist career career development cytokine immune system function improved improved outcome in vivo in vivo Model inhibitor insight lymphocyte proliferation meetings mouse model murine colitis pharmacologic programs protein complex protein protein interaction recruit research and development response responsible research conduct scaffold skills small molecule systemic inflammatory response transcription factor transcriptomics

项目摘要

The goal of this career development award is for the applicant to gain knowledge and technical expertise in lymphocyte biology in order to advance our understanding of how the interaction between BCL10 and MALT1, two critically important lymphocyte signaling proteins, influences lymphocyte function and dysfunction. Knowledge gained during this career development award will provide new insights into the mechanism of interaction between BCL10 and MALT1 as well as the molecular pathogenesis of immune disorders associated with MALT1 dysregulation, including psoriasis and colitis. Experiments are designed with the ultimate goal of determining the therapeutic potential of targeting the BCL10-MALT1 protein-protein interaction in these inflammatory disorders. Specifically, the proposed studies will investigate how manipulation of the BCL10- MALT1 interaction affects MALT1 activity, proinflammatory lymphocyte signaling, and progression of psoriasis and colitis. The proposed experimental aims utilize sophisticated protein biochemistry techniques, in-depth in vitro analyses of lymphocyte function, robust in vivo models of inflammatory disease, and detailed bioinformatic analyses. The applicant has selected a mentor and co-mentor who have strong track records of both research mentorship and scientific achievement and who are therefore well positioned to provide expert guidance. Additionally, the applicant has constructed a career mentoring committee with expertise in developing small molecule protein-protein interaction inhibitors, in lymphocyte biology, and in the analysis of animal models of inflammatory disease. The applicant has also identified key collaborators with needed expertise in immune dysfunction in psoriasis and in biostatistics. The University of Pittsburgh provides a fantastic environment in which to launch an independent career as a productive biomedical scientist. The primary mentor and co-mentor are committed to guiding the applicant towards a highly successful career as a physician scientist via a formal program of scientific and professional milestone assessments. Key milestones emphasize the mastery of specific scientific techniques, the development of research mentoring skills, the transition to senior/corresponding authorship of scientific manuscripts and the preparation of the applicant to initiate her own independent laboratory program. The applicant’s career development plan was carefully crafted to take full advantage of the outstanding environment at University of Pittsburgh including graduate level course work in immunology and biochemistry, workshops and formal coursework in bioinformatics, didactics in murine models of disease, face- to-face career development workshops offered through the Office of Academic Career Development, and workshops in Responsible Conduct of Research. The applicant has identified opportunities to present her work locally as well as at national meetings. With full support of her mentor and co-mentor, the applicant is excited to pursue this training in order to launch her career as an independent scientist studying the influence of key protein- protein interactions in lymphocyte function and dysfunction at the University of Pittsburgh.

该职业发展奖的目标是让申请人获得以下领域的知识和技术专长：淋巴细胞生物学，以加深我们对 BCL10 和 MALT1 之间如何相互作用的理解，两种极其重要的淋巴细胞信号蛋白，影响淋巴细胞功能和功能障碍。在此职业发展奖中获得的知识将为了解这一机制提供新的见解 BCL10 和 MALT1 之间的相互作用以及相关免疫疾病的分子发病机制 MALT1 失调，包括牛皮癣和结肠炎，实验的最终目标是：确定针对这些疾病中 BCL10-MALT1 蛋白-蛋白相互作用的治疗潜力具体来说，拟议的研究将调查如何操纵 BCL10-。 MALT1 相互作用影响 MALT1 活性、促炎淋巴细胞信号传导和银屑病进展拟议的实验目标利用复杂的蛋白质生物化学技术，深入研究。淋巴细胞功能的体外分析、炎症性疾病的稳健体内模型以及详细的生物信息学申请人选择了一位在这两项研究方面都有良好记录的导师和共同导师。指导和科学成就，因此谁有能力提供专家此外，申请人还建立了一个具有发展专业知识的职业指导委员会。小分子蛋白质-蛋白质相互作用抑制剂，用于淋巴细胞生物学和动物模型分析申请人还确定了在免疫方面具有所需专业知识的关键合作者。匹兹堡大学在银屑病和生物统计学方面提供了绝佳的环境。作为一名富有成效的生物医学科学家开始独立的职业生涯。致力于引导申请人通过正式的医学科学家职业生涯取得高度成功科学和专业的里程碑评估计划关键里程碑强调对具体内容的掌握。科学技术、研究指导技能的发展、向高级/相应职位的过渡科学手稿的作者身份以及申请人为启动自己的独立性所做的准备申请人的职业发展计划经过精心设计，以充分利用实验室项目。匹兹堡大学的优越环境包括免疫学和研究生水平的课程生物化学、生物信息学讲习班和正式课程、小鼠疾病模型教学、面部通过学术职业发展办公室提供的面对面职业发展研讨会，以及负责任的研究行为研讨会申请人已找到展示其工作的机会。在她的导师和共同导师的全力支持下，申请人很高兴能够在当地和全国会议上参加。接受这项培训是为了开始她作为一名独立科学家的职业生涯，研究关键蛋白质的影响- 匹兹堡大学淋巴细胞功能和功能障碍中的蛋白质相互作用。