Storming Immune Monogenic Conditions through Multiomic and Gene Editing Approaches

通过多组学和基因编辑方法攻克免疫单基因条件

• 批准号: EP/Y032500/1
• 负责人: Roser Vento Tormo
• 金额: $ 33.22万
• 依托单位: Wellcome Sanger Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY032500%2F1
• 关键词: Storming; Immune; Monogenic; Conditions; through

The human immune system controls the efficiency to respond to infections and eliminate aberrant cells, such as cancer cells. Immunefunction depends on the balanced contribution of many genes, encoding for receptors, cytokines, cell signalling molecules andtranscription factors and are modulated by a wide range of environmental and epigenetic factors. Monogenic mutations for immunerelated genes, also known as Inborn Errors of Immunity (IEI), provide unique examples for understanding immune fitness. IEI,individually considered as rare diseases, constitute a group of >400 immune disorders with a combined prevalence similar toleukemias (1/1,000-1/5,000). For a given mutated gene, IEI patients can display a wide range of phenotypic expressivity (fromasymptomatic to severely impaired) and different responses to treatments. Therefore, there is an unmet need to address the wideunderlying impact of IEI. Previous EU consortia have not addressed these questions in full. It is therefore needed a new generation ofresearchers, equipped with a complete set of scientific, technological and strategic skills; and a wide vision to face the outstandingchallenges in the IEI field. To this end, the IMMERGE MSCA DN combines the talent of leaders from different clinical and basic researchand biotech environments to train 11 doctoral candidates. Through our research activity and training activities, we will address keychallenges in the field: 1) To assess the functional impact of IEI in different immune cell types through single cell and bulk multiomics.2) To develop computational tools for dissecting the altered cellular pathways underlying specific IEI. 3) To genetically correct ormodel IEI and develop pre-clinical models. With our strategy, IMMERGE will generate an outstanding network of professionals able todevelop impactful studies that will change the field, generate tools for personalised medicine and generate awareness in the societyand influence policy makers

人体免疫系统控制着对感染做出反应并消除异常细胞（例如癌细胞）的效率。免疫功能取决于许多编码受体、细胞因子、细胞信号分子和转录因子的基因的平衡贡献，并受到多种环境和表观遗传因素的调节。免疫相关基因的单基因突变，也称为先天性免疫错误 (IEI)，为了解免疫适应性提供了独特的例子。 IEI 被单独认为是罕见疾病，由超过 400 种免疫疾病组成，其综合患病率与白血病相似 (1/1,000-1/5,000)。对于给定的突变基因，IEI 患者可以表现出多种表型表达性（从无症状到严重受损）和对治疗的不同反应。因此，解决 IEI 广泛的潜在影响的需求尚未得到满足。此前的欧盟财团尚未全面解决这些问题。因此，需要具备一整套科学、技术和战略技能的新一代研究人员；以及面对 IEI 领域突出挑战的广阔视野。为此，IMMERGE MSCA DN 结合了来自不同临床和基础研究以及生物技术环境的领导人才，培养了 11 名博士生。通过我们的研究活动和培训活动，我们将解决该领域的关键挑战：1) 通过单细胞和批量多组学评估 IEI 对不同免疫细胞类型的功能影响。2) 开发计算工具来剖析潜在的改变的细胞途径具体的IEI。 3）对IEI进行基因校正或建模并开发临床前模型。通过我们的战略，IMMERGE 将建立一个杰出的专业人士网络，能够开展有影响力的研究，从而改变该领域、生成个性化医疗工具、提高社会意识并影响政策制定者