Stability and phase transitions of protein solutions.

蛋白质溶液的稳定性和相变。

• 批准号: 2610906
• 金额: --
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2610906
• 关键词: Stability; phase; transitions; protein; solutions.

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.

项目描述从风险形式供您适应：蛋白质的稳定性对于正常的生物学功能以及生物制药药物的储存和递送至关重要。但是，评估稳定性可能具有挑战性，因为它既与蛋白质的结构稳定性及其溶液稳定性有关。许多挑战涉及可以充分解决这两者的技术的相对稀疏性，通常会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。但是，某些技术（例如固有荧光和圆形二色性（CD））可以比其他方法具有显着优势，因为它们都需要相对较少的样品。间接地，蛋白质相变的位置可以提供有关其相对稳定性的信息，并可以提高蛋白质溶液稳定性的可预测性。 30年前，在眼镜透镜中描述了晶体蛋白的液态液相分离（LLP）。 LLP是生物学中的重要相变，因此对于结晶而言是可稳定的，因此也是蛋白质稳定性的良好代理。 LLP是由于在眼镜中发现的伽马结晶蛋白之间的净短距离脉冲蛋白之间的净远程相互作用而导致的，并且在纯化的人γd晶体蛋白（HGD）溶液中都发生在体外和alpha，beta和beta，beta和beta和beta和beta，beta和beta，beta和beta的复杂混合物中在眼镜纤维中发现的伽马结晶蛋白。最近，由于对研究细胞细胞器中液相分离的重新兴趣，这些过程对文献引起了重大兴趣。 在将与应用光物理学合作进行的该项目中，我们将使用多种技术探索几种球状和合成蛋白的稳定性和相变，包括通过应用光物理学开发的技术。在使用应用光物理学开发的工具探索蛋白质相变和展开时，我们将帮助指导其产品开发并发表我们的作品，为用户提供如何在其自己的研究中使用这些仪器的示例。该项目属于EPSRC物理科学研究领域。