Twinning for Excellence in Research, Training and Innovation in Protein Misfolding Diseases

蛋白质错误折叠疾病是由蛋白质错误折叠引起的一大类人类疾病，包括阿尔茨海默病、系统性淀粉样变性、肥胖症、囊性纤维化、视网膜色素变性和2型糖尿病等严重的社会经济影响的疾病。其中绝大多数仍然无法治愈，因此目前非常需要开发针对它们的有效疗法。在已知的&gt；70个PMD中，大约三分之一是由于完整的膜蛋白(MPS)的错误折叠造成的。然而，众所周知，MPS在生化和结构上都很难过度表达、分离和研究，因此在(临床前)管道中只有很少的先导分子的情况下，构成了治疗干预的特别具有挑战性的靶点。此外，涉及PMDS的科学界仍然四分五裂，大多数研究针对的是可溶性蛋白质，只有一小部分相当孤立的亚社区专注于容易发生错误折叠的MPS。国家希腊研究基金会一直在利用合成生物学的力量，开发针对可溶性和膜蛋白错误折叠的有效技术。协调员希望在这些初步成功的基础上，与PMD和合成生物学研究方面的三个著名中心合作，以建立一个新的PMD研究、培训和创新方面的卓越中心，并巩固这一领域的科学界。通过这一过程，它将在PMD领域获得领先地位，并在以下方面与最先进的机构趋同：它产生的科学数据的质量，它发表的顶级科学论文的数量，它从有竞争力的来源获得的资金数额，它培训年轻科学家并为他们的职业发展做出贡献的效率，它交流研究活动结果并将其转化为高科技创业和社会实际成果的方式。

Protein misfolding diseases (PMDs) are a large group of human disorders caused by protein misfolding and include serious conditions with high socio-economic impact, such as Alzheimer’s disease, systemic amyloidosis, obesity, cystic fibrosis, retinitis pigmentosa and type 2 diabetes. The vast majority of them remain incurable so there is currently a great need for the development of effective therapeutics against them. Among the >70 known PMDs, about one third occur due to the misfolding of integral membrane proteins (MPs). MPs, however, are notoriously difficult to overexpress, isolate and study, both biochemically and structurally, thus constituting particularly challenging targets for therapeutic intervention with only few lead molecules in (pre)clinical pipelines. Furthermore, the scientific community involved in PMDs remains fragmented, with the majority of research targeting soluble proteins and only a small, rather isolated, sub-community focusing on misfolding-prone MPs. The National Hellenic Research Foundation has been exploiting the power of synthetic biology to develop efficient technologies targeting the misfolding of both soluble and membrane proteins. The coordinator wishes to build on these initial successes to partner with three prominent centers in PMD and synthetic biology research in order to establish a new excellence hub in research, training and innovation in PMDs and consolidate the scientific community in this field. Through this process, it will acquire a position among the leaders in the field of PMDs and converge with the most advanced institutions in terms of the quality of scientific data it produces, number of top-tier of scientific papers it publishes, amount of funding it secures from competitive sources, efficiency with which it trains its young scientists and contributes to their career development, the way it communicates the results of its research activity and converts them to tangible outcomes for high-tech entrepreneurship and the societyno public description