PhD Studentship in Biomimetic Colloid Science

水溶液中大分子之间的相互作用是一种复杂的现象，控制着许多重要的化学和生物过程。例如，蛋白质分子间的相互作用决定了它们的时空分布，如簇的形成、聚集和液-液相分离。尽管蛋白质表面上的非极性残基的百分比可高达70%，但蛋白质的细胞浓度保持在极高水平，即高达40%的体积分数。相比之下，大多数合成胶体系统在如此高的浓度下沉淀，这是由于各种吸引力的相互作用和库仑排斥的电解质屏蔽。在水基化学和生物环境中最重要的力之一是疏水相互作用，如在脂质双层组织和蛋白质折叠中所显示的。虽然在bionano接口至关重要，但其基本原理尚未完全理解。在我们的小组中，我们开发了一个模块化平台，该平台基于用不稳定的封端剂合成金纳米颗粒，然后用目标硫醇配体的规定混合物进行后续官能化。这种方法不仅迎合定制的纳米级胶体与可调配体壳，但也提供了小角X射线散射（SAXS）由于显着的散射长度密度的Au核心的胶体现象的调查。然后，获得的散射曲线可以用于通过机器学习算法（合作进行）提取胶体相互作用项。根据一些初步工作（并与补充技术相结合），这个模型系统提供了独特的机会，以解开胶体现象中发现的性质与相关的基础科学，但也各种工业应用（例如在药物递送，生物传感，食品科学和个人护理）。该项目将在这些初步研究的基础上建立一个综合的合成和分析方法，以模拟自然界中发现的胶体相互作用。并解开它们不同寻常的特性。为此，工作将分4个阶段进行：第1阶段。平台开发（1-12个月）。viva升级前的第一年将致力于平台开发，即-合成具有低分散性、可调核尺寸和可适应配体壳的合适金纳米颗粒-通过SAXS研究胶体稳定性-实施机器学习算法，用高级模型解释SAXS数据（扩展的DLVO理论）培训将是至关重要的，与合作者设想延长停留时间（数据科学：基思巴特勒博士，QMUL; SAXS：斯特凡福斯特教授）以及参加夏季/冬季学校与社区接触。这一阶段将完成起草和防御的升级万岁。 第二阶段解开蛋白质溶解度（第13-24个月）。在第1阶段获得的知识将有助于通过匹配大小和配体组成来创建天然蛋白质的精确模拟物。两亲分子将作为助水溶物，以研究胶体稳定性的关键因素，并将其用于金纳米颗粒溶解度的新记录。研究结果将用于与计算同事的合作，如约克大学的Seishi Shimidzu博士。 第三阶段触发分子识别现象（第25-36个月）。博士学位的最后实验阶段目前设想用于研究天然环境中的分子识别。本文开发的实验工具包将通过使用石英晶体微天平与耗散监测的界面吸附现象的研究来补充。协同作用，预计与其他博士研究在我的小组，例如自动化和高通量表征。

The interactions between macromolecules in aqueous solutions are complex phenomena that govern many important chemical and biological processes. For example, the intermolecular interactions of proteins dictate their spatio-temporal distributions, such as cluster formation, aggregation and liquid-liquid phase separation. Although the percentage of non-polar residues on protein surfaces may be as high as 70%, the cellular concentrations of proteins are maintained at extremely high level, i.e. up to 40% in volume fraction. In comparison, most synthetic colloidal systems precipitate at such high concentrations due to various attractive interactions and electrolyte screening of Coulomb repulsion. One of the most important forces in water-based chemical and biological environments is the hydrophobic interaction as displayed in lipid bilayer organisation and protein folding. Although vital at the bionano interface, its underlying principles have not been fully understood. In our group, we have developed a modular platform, which is based on the synthesis of gold nanoparticles with a labile capping agent followed by subsequent functionalization with prescribed mixtures of target thiol ligands. This approach not only caters for tailored nanoscale colloids with tunable ligand shells but also offers the investigation of colloidal phenomena by small angle X-ray scattering (SAXS) due to the pronounced scattering length density of the Au core. The obtained scattering profiles can then be used to extract colloidal interaction terms via machine learning algorithms (carried out in collaboration). Based on some preliminary work (and in combination with complimentary techniques), this model system offers unique opportunities to unravel colloidal phenomena found in nature with relevance for fundamental science but also various industrial applications (e.g. in drug delivery, biosensing, food science and personal care).The project will build on these preliminary studies to establish an integrated synthetic and analytical approach to mimic colloidal interactions found in nature and unravel their unusual properties. To this end, the work will be carried out in 4 stages: Stage 1. Platform development (Month 1-12). The first year until the viva upgrade will be dedicated to platform development, i.e. - synthesis of suitable gold nanoparticles with low dispersity, tunable core size and adaptable ligand shell- investigation of colloidal stability by SAXS- implementation of machine learning algorithms to interpret SAXS data with advanced models (extended DLVO theory)Training will be critically important, with extended stays envisioned with collaborators (data science: Dr Keith Butler, QMUL; SAXS: Prof Stefan Förster) as well as participation in summer / winter schools to engage with the community. This phase will completed with the drafting and defense of the upgrade viva. Stage 2. Unravelling protein solubility (Month 13-24).Knowledge acquired in stage 1 will serve to create accurate mimics of natural proteins by matching of size and ligand composition. Amphiphilic molecules will serve as hydroptropes in order to study critical factors for colloidal stability and implement these for novel records of gold nanoparticle solubility. Findings will serve for collaborations with computational colleagues, such as Dr Seishi Shimidzu from the University of York. Stage 3. Triggered molecular recognition phenomena (Month 25-36). The final experimental stage of the PhD is currently envisioned to be used for the study of molecular recognition in native environments. The experimental tool-kit developed herein will be complemented by studies of interfacial adsorption phenomena using quartz crystal microbalance with dissipation monitoring. Synergies are expected with other PhD studies in my group, e.g. on automation and high throughput characterisation.