Combined Mass Spectrometric and Optical Spectroscopic Investigation of Biological Molecules in Controlled Micro-environments

识别分子并研究其性质的新工具和技术的开发和应用可能是变革性的，对从化学和物理到医学和生物学等领域产生长期影响。开发这样的工具是Jockusch实验室的研究目标。特别是，我们专注于开发新技术，扩展质谱（MS）的使用，以增强对生物分子（如蛋白质）如何受其环境影响的理解。这很重要，因为蛋白质在生物学中起着核心作用。例如，“错误折叠”的蛋白质对健康有负面影响，并与许多破坏性疾病有关，包括阿尔茨海默病和帕金森病。然而，蛋白质和其他生物分子通常不会孤立地发挥作用;它们的行为受到分子相互作用的复杂网络的调节。为了剖析自然界中存在的复杂性，研究简化的系统是有价值的，这些系统的复杂性可以以仔细控制的方式逐渐建立起来。因此，Jockusch实验室了解生物分子性质的方法是在高度受控的环境中研究它们：在质谱仪内隔离。这使得能够从分子环境的影响中分离固有的分子性质。在随后的研究中，分子环境的片段，如水分子，金属离子或其他结合伴侣将被添加以形成复合物和簇，从而能够发现其他特定的相互作用如何调节或控制感兴趣的分子特性。

The development and application of new tools and techniques to identify molecules and study their properties can be transformative, with long-term impact on fields ranging from chemistry and physics to medicine and biology. The development of such tools is the aim of research in the Jockusch laboratory. In particular, we focus on the development of new techniques that extend the uses of mass spectrometry (MS) in order to enhance the understanding of how biological molecules such as proteins are affected by their environment. This is important because proteins play a central role in biology. For example, proteins that are ‘misfolded’ have negative impacts on health, and are associated with many devastating diseases including Alzheimer’s and Parkinson’s diseases. However, proteins and other biomolecules do not generally act in isolation; their behavior is modulated by a complex web of molecular interactions. In order to dissect the complexity present in Nature, it is valuable to study simplified systems whose complexity can gradually be built up in a carefully controlled fashion. Thus, the Jockusch laboratory’s approach to understanding the properties of biomolecules is to study them in a highly-controlled environment: isolated inside a mass spectrometer. This enables the separation of intrinsic molecular properties from effects of the molecular environment. In subsequent investigations, pieces of the molecular environment such as water molecules, metal ion, or other binding partners will be added to form complexes and clusters, thus enabling discovery of how additional specific interactions modulate or control the molecular properties of interest.