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，蛋白质的分子间相互作用决定了它们的时空分布，如簇形成、聚集和液-液相分离。尽管蛋白质表面的非极性残基的百分比可能高达70%，但蛋白质的细胞浓度保持在极高的水平，即高达40%的体积分数。相比之下，由于各种吸引相互作用和电解质对库仑排斥的筛选，大多数合成胶体体系在如此高的浓度下沉淀。在水基化学和生物环境中最重要的力量之一是疏水相互作用，表现在脂质双分子层组织和蛋白质折叠中。尽管在生物纳米界面中至关重要，但其基本原理尚未完全理解。在我们的团队中，我们开发了一个模块化平台，该平台基于用不稳定的盖层剂合成金纳米粒子，然后用规定的目标硫醇配体混合物进行功能化。这种方法不仅适合于具有可调配体壳的纳米胶体，而且由于金核的明显散射长度密度，可以通过小角x射线散射（SAXS）研究胶体现象。获得的散射剖面可以通过机器学习算法（在合作中进行）用于提取胶体相互作用项。基于一些初步工作（并结合互补技术），该模型系统为揭示与基础科学相关的自然界中发现的胶体现象以及各种工业应用（例如药物输送，生物传感，食品科学和个人护理）提供了独特的机会。该项目将建立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来模拟自然界中发现的胶体相互作用，并揭示其不寻常的特性。为此，工作将分4个阶段进行：第一阶段。平台开发（1-12月）。在viva升级之前的第一年将致力于平台开发，即-合成具有低分散性，可调核心尺寸和适应性配体外壳的合适金纳米颗粒-通过SAXS研究胶体稳定性-实现机器学习算法以先进模型解释SAXS数据（扩展DLVO理论）培训将至关重要，并与合作者(数据科学：Keith Butler博士，QMUL；萨克斯：Stefan教授Förster)，以及参加暑期/冬季学校，与社区互动。这一阶段将完成升级脚本的起草和防御。阶段2。解开蛋白质溶解度（13-24月）。在第一阶段获得的知识将通过匹配大小和配体组成来创建天然蛋白质的精确模拟。两亲分子将作为亲水分子，以研究胶体稳定性的关键因素，并实现这些对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，例如来自约克大学的Seishi Shimidzu博士。阶段3。触发分子识别现象（25-36月）。博士学位的最后一个实验阶段目前预计将用于自然环境中的分子识别研究。本文开发的实验工具将辅以使用带有耗散监测的石英晶体微天平对界面吸附现象的研究。期望与我小组中的其他博士研究产生协同效应，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.