Stability and phase transitions of protein solutions.

风险表中的项目描述供您修改：蛋白质的稳定性对正常的生物功能和生物制药药物的储存和输送很重要。然而，评估稳定性可能具有挑战性，因为它既关系到蛋白质的结构稳定性，也关系到它的溶液稳定性。大部分挑战与能够充分解决这两个问题的技术相对较少有关，这通常导致生物制药行业中蛋白质稳定性的测试和表征的重大分析负担。然而，一些技术，如本征荧光和圆二色性（CD）可以提供比其他方法显著的优势，因为它们都是信息丰富的，需要相对较少的样本。蛋白质的相变位置间接提供了蛋白质相对稳定性的信息，提高了蛋白质溶液稳定性的可预测性。晶体蛋白的液-液相分离（LLPS）早在30多年前就被描述在眼晶状体中。LLPS是生物学中重要的相变，在结晶方面是亚稳态的，因此也是蛋白质稳定性的一个很好的代表。LLPS的发生是由于晶状体中发现的γ晶体蛋白之间的净短距离吸引蛋白间相互作用的结果，它发生在体外纯化的人γ D晶体蛋白（HGD）溶液中，也发生在晶状体纤维中发现的α、β和γ晶体蛋白的复杂混合物中。最近，由于对细胞器中液相分离的研究重新产生了兴趣，这些过程在文献中引起了极大的兴趣。在这个将与应用光物理合作进行的项目中，我们将使用包括应用光物理正在开发的技术在内的一系列技术来探索几种球状和合成蛋白质的稳定性和相变。在使用应用光物理正在开发的仪器来探索蛋白质相变和展开时，我们将帮助指导他们的产品开发，并通过发表我们的工作，为用户提供如何将这些仪器用于他们自己的研究的示例。该项目属于EPSRC物理科学研究领域。

Project description from Risk Form for you to adapt: The stability of proteins is important for normal biological function and for the storage and delivery of biopharmaceutical drugs. However, assessing stability can be challenging, since it relates both to the structural stability of the protein and its solution stability. Much of the challenge relates to the relative sparsity of techniques that can adequately address both, generally leading to a significant analytical burden for the testing and characterisation of protein stability in the biopharmaceutical industry. However, some techniques such as intrinsic fluorescence and circular dichroism (CD) can offer significant advantages over other approaches, in that they are both informative are require relatively little sample. Indirectly, the position of phase transition of protein can provide information on their relative stability and could improve predictability of protein solution stability. Liquid-liquid phase separation (LLPS) of crystallin proteins was described in the eye lens over 30 years ago. LLPS is an important phase transition in biology, and is metastable with respect to crystallization, so is therefore also a good proxy for protein stability. LLPS occurs as a result of net short ranged attractive inter-protein interactions between the gamma crystallin proteins found in the eye lens and occurs in both purified human gamma D crystallin (HGD) solutions in-vitro and in the complex mixture of alpha, beta and gamma crystallins found in eye lens fibres. Recently, due to renewed interest in studying liquid phase separation in cellular organelles, these processes have received significant interest in the literature. In this project, which will be conducted in collaboration with Applied Photophysics, we will explore stability and phase transitions of several globular and synthetic proteins using a combination of techniques, including those being developed by Applied Photophysics. In using instruments under development at Applied Photophysics to explore protein phase transitions and unfolding, we will help to guide their product development and by publishing our work, provide users with examples of how these instruments can be employed in their own research. This project falls within the EPSRC Physical Science research area.