Chemistry of Biological Nanoassemblies

生物体一直是设计用于医疗和纳米技术应用的生物材料的不可估量的灵感来源。内源性肽和蛋白质以其独特的自缔合能力而闻名，并且由此产生的超分子结构在宿主中执行重要的生理功能，如来自双壳软体动物的蜘蛛丝和足丝。加拿大生物纳米组装化学研究主席的总体目标是将蛋白质自组装的基础研究扩展到不同的超分子结构中，以操纵自我识别。我们将利用这些知识来设计用于疫苗接种的功能化蛋白质组装体，并探索（生物）纳米技术的创新机会。虽然拟议的研究计划主要集中在淀粉样纤维，但其他蛋白质纳米结构，如受细菌鞭毛和菌毛启发的蛋白质纳米结构，也将被工程化。淀粉样蛋白是高度组织化的蛋白质纳米结构，其在历史上与病理状态相关。在过去的十年中，几乎在所有物种中（从细菌到哺乳动物）都发现了完成基本生物活性的淀粉样蛋白结构。淀粉样蛋白的稳定性和机械性能表明，它们作为生物材料具有很大的潜力。然而，淀粉样蛋白的使用仍然受到限制，由于对自组装机制的不完全理解，难以控制最终的超分子结构以及缺乏对其生物学/免疫学特性的理解。为了解决这些问题，将进行以下具体目标：（i）设计操纵和探测淀粉样蛋白自组装的工具，（ii）利用交叉折叠组装来设计自佐剂化抗原递送系统，（iii）鉴定作为纳米疫苗支架的新型细菌自组装蛋白，（iv）扩大淀粉样蛋白原纤维的应用范围。由于其与疾病的历史关联，淀粉样蛋白尽管具有显著的性质，但作为生物材料受到的关注有限。通过结合（生物）化学，生物物理和生物学方法，该研究主席计划将导致策略来操纵蛋白质组装，并将发现新的功能。该计划将使这些蛋白质纳米结构的神秘化，促进其在疫苗设计和（生物）纳米技术中的应用。

Living organisms have always been an inestimable source of inspiration for the design of biomaterials for medical and nanotechnological applications. Endogenous peptides and proteins are known for their unique ability to self-associate and the resulting supramolecular structures are performing vital physiological functions in host, as exemplified by spider silk and byssus from bivalve molluscs. The overarching goal of the Canada Research Chair in Chemistry of Biological Nanoassemblies is to expand the fundamental study of protein self-assembly into different supramolecular architecture in order to manipulate self-recognition. We will take advantage of this knowledge to design functionalized proteinaceous assemblies for applications in vaccination and to explore innovative opportunities in (bio)nanotechnology. While the proposed research program mainly focuses on amyloid fibrils, other protein nanostructures, such as those inspired by bacterial flagella and pilus, will also be engineered. Amyloids are highly organized proteinaceous nanostructures that have been historically associated with pathological states. Over the last decade, amyloid structures that accomplish essential biological activities have been identified in almost all species, from bacteria to mammals. The stability and mechanical properties of amyloids suggest that they hold great potential as biomaterials. However, the use of amyloids is still limited by the incomplete understanding of the mechanisms of self-assembly, difficulty to control the final supramolecular architecture and lack of understanding of their biological/immunological properties. To address these issues, the following specific aims will be conducted: (i) design tools to manipulate and probe amyloid self-assembly, (ii) harness cross-ß-sheet assemblies to design self-adjuvanted antigen delivery system, (iii) identify novel bacterial self-assembling proteins as nanovaccine scaffolds, (iv) expand the scope of applications for amyloid fibrils. Due to their historical association with diseases, amyloids have gathered limited attention as biomaterials despite their remarkable properties. By combining (bio)chemical, biophysical and biological approaches, this research chair program will lead to strategies to manipulate proteinaceous assemblies and will uncover novel functionalities. This program will allow the demystification of these protein nanostructures, fostering their applications in vaccine design and (bio)nanotechnology.