Using biophysical methods and chemical biology to explore function and design in the tandem-repeat protein class

我们的主要研究重点是一类蛋白质，被称为串联重复蛋白，具有非常独特的结构（如锚蛋白，四肽和犰狳重复）。这些蛋白质在癌症、呼吸系统和心血管疾病等人类疾病中经常不受控制。重复蛋白的各个模块以线性方式堆叠，产生高度细长的超螺旋结构，从而为分子识别提供了一个扩展的支架。“脚手架”一词意味着一种刚性的建筑；然而，正如它们像弹簧一样的形状所表明的那样，人们认为重复阵列利用了更多的动态和弹性模式。重复序列蛋白质的简单模块化结构使它们独特地适合于对其生物物理特性的解剖以及对这些特性的合理重新设计。博士项目将从轮换项目继续进行，目标是将新功能嫁接到重复蛋白支架中。关键技术将是蛋白质工程、生物物理分析和x射线晶体学。细胞生物学将用于测试设计的蛋白质及其功能。我们也在考虑与Luca Pellegrini博士（生物化学系）合作一个项目。ENWW将主要涉及实验数据的统计分析。为此，将使用统计工具，如R。

Theme: World-Class Underpinning BioscienceThe major focus of our research is a class of proteins, known as tandem-repeat proteins, with very distinctive architecture (e.g. ankyrin, tetratricopeptide and armadillo repeats). These proteins are frequently deregulated in human diseases such as cancers and respiratory and cardiovascular diseases. The individual modules of repeat proteins stack in a linear fashion to produce highly elongated, superhelical structures, thereby presenting an extended scaffold for molecular recognition. The term 'scaffold' implies a rigid architecture; however, as suggested by their Slinky spring-like shapes, it is thought that repeat arrays utilise much more dynamic and elastic modes of action. The simple modular architecture of repeat proteins makes them uniquely amenable to the dissection of their biophysical properties as well as the rational redesign of these properties. The PhD project will continue from the rotation project with the goals of grafting new functions into repeat-protein scaffolds. Key techniques will be protein engineering, biophysical analysis and X-ray crystallography. Cell biology will be used to test the designed proteins and their function. We are also thinking about a collaborative project with Dr. Luca Pellegrini (Department of Biochemistry).ENWW will mainly involve statistical analysis of experimental data. For this purpose, statistical tools, such as R, will be used.