Towards a new era for the identification and characterisation of inborn errors of glycosylation

迈向先天性糖基化错误的识别和表征的新时代

• 批准号: 423366611
• 负责人: Professor Dr. Uwe Kornak
• 金额: --
• 依托单位: Katholieke Universiteit Leuven
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/423366611?language=en
• 关键词: Towards; new; era; identification; characterisation

Glycosylation is a chemical modification of proteins in our cells. It affects their stability and function. Thousands of proteins are ‘glyco-proteins’. As a result, genetic defects in glycosylation pathways lead to mostly severe diseases, called ‘Congenital Disorders of Glycosylation’ (CDG). With more than 100 different types, CDG has become an impressive group of metabolic diseases.On the one hand, we have patients with clear glycosylation anomalies, whose genetic defects remain elusive. We plan to use genomic tools to identify new genes and new disease mechanisms. On the other hand, we believe that many other patients with symptoms that fit with CDG (like intellectual disabilities, multiple congenital anomalies, bleeding disorders etc.), may have a glycosylation disorder that presently escapes diagnosis because the diagnostic tools are insufficient. We will develop new biomarkers based on glycomics, glycopeptidomics and metabolomics. In addition, fundamental research into the biochemistry of the sugars may lead to the identification of completely novel types of diseases. The ultimate goal is to treat or cure CDG patients. Since the cellular compartments where glycosylation occurs cannot easily be reached with therapeutic compounds, a causative treatment is difficult. Therefore, a better understanding of the pathophysiology of the different types of CDG is crucial for the development of novel therapeutic interventions. To this end we will systematically study already available cellular and mouse models using state-of-the-art omics approaches.. EUROGLYCAN-omics brings together a multidisciplinary group of clinical and basic researchers who have proven to be able to collaborate. We want to achieve the ambitious goals set here, for the sake of the patients and their families.

糖基化是我们细胞中蛋白质的化学修饰。影响其稳定性和功能。成千上万的蛋白质是“糖蛋白”。因此，糖基化途径中的遗传缺陷导致大多数严重疾病，称为“先天性糖基化障碍”（CDG）。CDG有100多种不同的类型，已经成为一组令人印象深刻的代谢疾病。一方面，我们有明确的糖基化异常的患者，其遗传缺陷仍然难以捉摸。我们计划使用基因组工具来识别新的基因和新的疾病机制。另一方面，我们认为，许多其他患者的症状符合CDG（如智力残疾，多种先天性异常，出血性疾病等），可能患有糖基化障碍，由于诊断工具不足，目前无法诊断。我们将在糖组学、糖肽组学和代谢组学的基础上开发新的生物标志物。此外，对糖的生物化学的基础研究可能会导致识别全新类型的疾病。 最终目标是治疗或治愈CDG患者。由于糖基化发生的细胞区室不容易用治疗性化合物到达，因此病因治疗是困难的。因此，更好地了解不同类型的CDG的病理生理学对于开发新的治疗干预措施至关重要。为此，我们将使用最先进的组学方法系统地研究已经可用的细胞和小鼠模型。 EUROGLYCAN-omics汇集了一个多学科的临床和基础研究人员小组，他们已经被证明能够合作。我们希望实现这里设定的雄心勃勃的目标，为了病人和他们的家人。