Recombinant metalloproteins and living cells for chemical research

在化学和生物学（“化学生物学”）之间的界面研究利用化学的力量来帮助理解生物系统中固有的复杂性。 化学生物学是一个令人兴奋的研究领域，现在是化学科学研究的主导主题。 这一领域的竞争性研究需要常规使用各种细胞系的培养和分离以及用于诱导和合成重组金属蛋白的细胞孵育所需的设备。 这项建议涉及购买这种设备，这是至关重要的，在UWO化学系的大量研究人员。 有了这台新设备，申请人将进行大量的研究。 使用重组金属蛋白Stillman将探测金属依赖性蛋白质折叠和金属依赖性代谢功能的细节，特别是在神经生理学和Konermann将研究作为淀粉样蛋白聚集体的原因的蛋白质错误折叠的影响，这被认为是在阿尔茨海默病和脑生理学中发挥重要作用。 界面研究的一个非常活跃的领域涉及整个活细胞和细胞膜的化学性质。 吉利斯将开发新的抗生素，这种抗生素通过破坏细菌细胞膜来发挥作用。 活细胞的分子水平研究是Norton，Lagugné-Labarthet和Ding研究的主要目标，其中显微镜的化学和技术发展将用于活细胞特性的新研究。 这些发展将导致新的成像模式，能够纳米空间分辨率，高时间分辨率和单分子检测。 丁和克拉茨将研究化学物质对活细胞代谢活动的影响。 总之，所要求的设备将为大量研究人员提供迄今为止尚无法获得的设施，使其能够合成重组蛋白质和生长细胞模型，这将导致我们在理解生物分子和结构及其功能之间的关系方面取得令人兴奋的进展。

Research at the interface between chemistry and biology ("chemical biology") utilizes the power of chemistry to help understand the complexity inherent in biological systems. Chemical biology is an exciting area of study that is now a dominant theme in research in the chemical sciences. Competitive research in this area requires routine access to the equipment required for the culture and isolation of a variety of cell lines and the incubation of cells for induction and synthesis of recombinant metalloproteins. This proposal concerns purchase of this equipment, which is of crucial importance to a large number of researchers in the UWO Chemistry Department. With this new equipment, the applicants will carry out a large number of research studies. Using recombinant metalloproteins Stillman will probe the details of metal-dependent protein folding and metal-dependent metabolic function, particularly in neurophysiology and Konermann will study the effects of misfolding of proteins as the cause of amyloid protein aggregates, which are considered to play a vital role in Alzheimer's disease, and in brain physiology. An extremely active area of interfacial research concerns the chemical properties of whole living cells and cell membranes. Gillies will develop novel antibiotics, which act by disrupting the membranes of bacterial cells. The molecular level study of live cells is a major objective in the research of Norton, Lagugné-Labarthet and Ding in which chemical and technical developments in microscopy will be used for novel research on the properties of living cells. These developments will lead to new imaging modalities capable of nanometer spatial resolution, high temporal resolutions, and single molecule detection. Ding and Kraatz will study the effects of chemicals on the metabolic activities of living cells. In summary, the requested equipment will provide a hitherto unavailable facility for a large number of researchers allowing the synthesis of recombinant proteins and growth of cell models that will lead to exciting progress to be made in our understanding of the relationships between biological molecules and structures, and their functions.