Manipulating amyloid self-assembly: toward the design of functionalized proteinaceous nanostructures
操纵淀粉样蛋白自组装:面向功能化蛋白质纳米结构的设计
基本信息
- 批准号:RGPIN-2018-06209
- 负责人:
- 金额:$ 2.62万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2022
- 资助国家:加拿大
- 起止时间:2022-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Endogenous proteins are known for their ability to self-associate in living organisms into supramolecular structures that perform vital physiological functions. Over the last decade, amyloid structures that accomplish crucial biological activities have been identified in almost all species, from bacteria to mammals. Amyloids are highly organized proteinaceous assemblies that are characterized by a cross-beta-sheet quaternary conformation in which individual beta-strands are running perpendicular to the fibril axis. The mechanical, physical and biological properties of amyloids suggest that they hold great potential as nanomaterials for (bio)technological applications. For instance, amyloid based-materials were recently evaluated as scaffold for cell growth, drug delivery systems and nanosensors. Despite their tremendous potential as functional advanced soft materials, the usage of amyloids in nanomedicine and nanotechnology is still today limited by a number of issues, which include; (i) incomplete understanding of the mechanisms of self-assembly, (ii) difficulty to control amyloid formation and (iii) challenge to predict the supramolecular architecture from the peptide sequence. In this context, the overarching goal of this research program is to uncover innovative strategies to manipulate peptide self-assembly and to construct highly ordered functionalized proteinaceous nanostructures. Toward this goal, the three following specific aims will be addressed: 1. Identify strategies to modulate the (supra)molecular architecture of peptide assemblies 2. Conceive chemical approaches to probe and temporally photocontrol amyloid formation 3. Implement chemoselective methods to orthogonally functionalize proteinaceous nanostructures Life-inspired protein assemblies, including amyloids, have recently received a huge increase of interest for the design of supramolecular structures. This research program will lead to novel strategies to construct functional proteinaceous nanostructures and will contribute to the fundamental knowledge of amyloid formation. By studying the roles of conformational and physicochemical properties in molecular self-assembly, we aim at fine-tuning the amyloid suprastructure with a precise design at the molecular level. By developing conformational-sensitive probes and photoresponsive elements, we will support a better understanding of the driving forces that kinetically control assembly. Overall, this program will transform the perception of the scientific community towards these fascinating nanostructures, fostering the applications of functional amyloid-based advanced biomaterials. Accordingly, this program will open to novel research opportunities and innovative applied avenues for Canada's nanotechnology, life sciences and biopharmaceutical sectors.
内源性蛋白质以其在活生物体中自我缔合成执行重要生理功能的超分子结构的能力而闻名。在过去的十年中,几乎在所有物种中(从细菌到哺乳动物)都发现了完成关键生物活性的淀粉样蛋白结构。淀粉样蛋白是高度组织化的蛋白质组装体,其特征在于交叉β折叠四级构象,其中单个β链垂直于原纤维轴延伸。淀粉样蛋白的机械、物理和生物学特性表明,它们作为纳米材料在(生物)技术应用中具有巨大的潜力。例如,淀粉样蛋白基材料最近被评估为用于细胞生长、药物递送系统和纳米传感器的支架。尽管淀粉样蛋白作为功能先进的软材料具有巨大的潜力,但其在纳米医学和纳米技术中的使用仍然受到许多问题的限制,这些问题包括:(i)对自组装机制的不完全理解,(ii)难以控制淀粉样蛋白的形成和(iii)从肽序列预测超分子结构的挑战。在这种情况下,这项研究计划的总体目标是发现创新的策略来操纵肽自组装和构建高度有序的功能化蛋白质纳米结构。为了实现这一目标,将解决以下三个具体目标:1。确定策略,以调节(超)分子结构的肽组件2。设想化学方法来探测和暂时光控淀粉样蛋白的形成3。实施化学选择性方法正交功能化蛋白质纳米结构生命灵感蛋白质组装体,包括淀粉样蛋白,最近收到了巨大的兴趣增加的超分子结构的设计。这项研究计划将导致新的策略,以构建功能性蛋白质纳米结构,并将有助于淀粉样蛋白形成的基础知识。通过研究分子自组装过程中构象和物理化学性质的作用,我们的目标是在分子水平上对淀粉样蛋白的超结构进行精确的设计。通过开发构象敏感的探针和光响应元件,我们将支持更好地了解动力学控制组装的驱动力。总的来说,该计划将改变科学界对这些迷人的纳米结构的看法,促进基于功能性淀粉样蛋白的先进生物材料的应用。因此,该计划将为加拿大的纳米技术,生命科学和生物制药部门提供新的研究机会和创新的应用途径。
项目成果
期刊论文数量(0)
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Bourgault, Steve其他文献
Role of Site-Specific Asparagine Deamidation in Islet Amyloid Polypeptide Amyloidogenesis: Key Contributions of Residues 14 and 21
- DOI:
10.1021/acs.biochem.7b00209 - 发表时间:
2017-07-25 - 期刊:
- 影响因子:2.9
- 作者:
Phuong Trang Nguyen;Zottig, Ximena;Bourgault, Steve - 通讯作者:
Bourgault, Steve
Engineering and evaluation of amyloid assemblies as a nanovaccine against the Chikungunya virus
- DOI:
10.1039/c8nr05948a - 发表时间:
2018-11-07 - 期刊:
- 影响因子:6.7
- 作者:
Babych, Margaryta;Bertheau-Mailhot, Genevieve;Bourgault, Steve - 通讯作者:
Bourgault, Steve
Thioflavin T fluorescence to analyse amyloid formation kinetics: Measurement frequency as a factor explaining irreproducibility
- DOI:
10.1016/j.ab.2017.06.007 - 发表时间:
2017-09-01 - 期刊:
- 影响因子:2.9
- 作者:
Sebastiao, Mathew;Quittot, Noe;Bourgault, Steve - 通讯作者:
Bourgault, Steve
Biological and Structural Analysis of Truncated Analogs of PACAP27
- DOI:
10.1007/s12031-008-9081-7 - 发表时间:
2008-11-01 - 期刊:
- 影响因子:3.1
- 作者:
Bourgault, Steve;Vaudry, David;Fournier, Alain - 通讯作者:
Fournier, Alain
Identification of a hinge residue controlling islet amyloid polypeptide self-assembly and cytotoxicity
- DOI:
10.1074/jbc.ra118.006454 - 发表时间:
2019-05-24 - 期刊:
- 影响因子:4.8
- 作者:
Godin, Elizabeth;Phuong Trang Nguyen;Bourgault, Steve - 通讯作者:
Bourgault, Steve
Bourgault, Steve的其他文献
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{{ truncateString('Bourgault, Steve', 18)}}的其他基金
Chemistry of Biological Nanoassemblies
生物纳米组件的化学
- 批准号:
CRC-2021-00112 - 财政年份:2022
- 资助金额:
$ 2.62万 - 项目类别:
Canada Research Chairs
Chemistry of Biological Nano-Assemblies
生物纳米组件的化学
- 批准号:
CRC-2016-00033 - 财政年份:2022
- 资助金额:
$ 2.62万 - 项目类别:
Canada Research Chairs
Chemistry Of Biological Nano-Assemblies
生物纳米组件的化学
- 批准号:
CRC-2016-00033 - 财政年份:2021
- 资助金额:
$ 2.62万 - 项目类别:
Canada Research Chairs
Manipulating amyloid self-assembly: toward the design of functionalized proteinaceous nanostructures
操纵淀粉样蛋白自组装:面向功能化蛋白质纳米结构的设计
- 批准号:
RGPIN-2018-06209 - 财政年份:2021
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Chemistry of Biological Nano-Assemblies
生物纳米组件的化学
- 批准号:
CRC-2016-00033 - 财政年份:2020
- 资助金额:
$ 2.62万 - 项目类别:
Canada Research Chairs
Manipulating amyloid self-assembly: toward the design of functionalized proteinaceous nanostructures
操纵淀粉样蛋白自组装:面向功能化蛋白质纳米结构的设计
- 批准号:
RGPIN-2018-06209 - 财政年份:2020
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Chemistry of Biological Nano-Assemblies
生物纳米组件的化学
- 批准号:
CRC-2016-00033 - 财政年份:2019
- 资助金额:
$ 2.62万 - 项目类别:
Canada Research Chairs
Manipulating amyloid self-assembly: toward the design of functionalized proteinaceous nanostructures
操纵淀粉样蛋白自组装:面向功能化蛋白质纳米结构的设计
- 批准号:
RGPIN-2018-06209 - 财政年份:2019
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Manipulating amyloid self-assembly: toward the design of functionalized proteinaceous nanostructures
操纵淀粉样蛋白自组装:面向功能化蛋白质纳米结构的设计
- 批准号:
RGPIN-2018-06209 - 财政年份:2018
- 资助金额:
$ 2.62万 - 项目类别:
Discovery Grants Program - Individual
Chemistry of Biological Nano-Assemblies
生物纳米组件的化学
- 批准号:
CRC-2016-00033 - 财政年份:2018
- 资助金额:
$ 2.62万 - 项目类别:
Canada Research Chairs
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