THE STRUCTURES OF LARGE BIOMOLECULES AND BIOMOLECULAR SYSTEMS

在我的实验室工作的MBRS学生将有机会工作 在一个或多个项目，调查结构， 生物分子和生物系统。他们会独立学习 实施生物医学和生物技术中使用的基本技术 research.根据学生以前的经验和兴趣， 它们可能积极参与蛋白质纯化、等电 聚焦、定性和制备型聚丙烯酰胺凝胶电泳， 离子交换色谱和尺寸排阻色谱。具体 项目可能涉及蛋白质结晶实验，单晶 X射线衍射实验，计算方法，如分子 替代方法和分子建模，蛋白质/脂质的制备 在电子显微镜下观察的单层系统的操作 电镜、脂质体制备和X射线散射 脂质体实验利用x射线衍射电子显微镜 方法和计算方法，我们正在进行结构研究， 白喉毒素片段A和B，以及艰难梭菌毒素A。 从我们的研究中，我们希望更好地了解高分子量， 亲水性分子如细菌蛋白毒素能够 跨细胞膜转运并影响它们的细胞 目标的细菌蛋白毒素的结构信息也可能 在免疫毒素的设计中， 癌症和相关疾病中的细胞。作为综合研究的一部分， 脂质体为基础的药物输送系统，我们使用X射线散射 研究AmBisome结构特性的方法，AmBisome由 维斯塔公司AmBisome用于治疗全身性真菌感染 在艾滋病发病期间或器官受免疫抑制后 移植手术本研究的目的是阐明脂质体 治疗药物的结构特性和分子间相互作用 与脂质双层。这将有助于我们更好地了解 脂质体摄取、加工和反应性，并允许将来合理 设计最佳的药物输送系统以对抗癌症和相关疾病 疾病

MBRS students working in my laboratory will have the opportunity to work on one or more of several projects that investigate structures of biomolecules and biological systems. They will learn and independently implement essential techniques used in biomedical and biotechnological research. Depending on the students' previous experiences and interests, they may be actively involved in protein purification, isoelectric focussing, qualitative and preparative polyacrylamide gel electrophoresis, ion exchange chromatography and size exclusion chromatography. Specific projects may involve protein crystallization experiments, single-crystal x-ray diffraction experiments, computational approaches such as molecular replacement methods and molecular modeling, preparation of protein/lipid monolayer systems for viewing under an electron microscope, operation of an electron microscope, preparation of liposomes and x-ray scattering experiments on liposomes. Using x-ray diffraction, electron microscopic methods and computational approaches, we are conducting structural studies on diphtheria toxin fragments A and B, and Clostridium difficile toxin A. From our studies we hope to better understand how high molecular weight, hydrophilic molecules such as bacterial protein toxins are capable of translocation across cellular membranes and effecting their cellular targets. Structural information about bacterial protein toxins may also aid in the design of immunotoxins, molecules efficient in killing specific cells in cancer and related diseases. As part of an integrated study of liposomal-based drug delivery systems, we are using x-ray scattering methods to investigate the structural properties of AmBisome, produced by Vestar, Inc. AmBisome is used to treat systemic fungal infections brought on by immune suppression during the onset of AIDS or after organ transplant surgery. The goal of this research is to elucidate liposome structural properties and the inter-molecular interactions of therapeutic agents with the lipid bilayer. This will help us to better understand liposome uptake, processing and reactivity, and allow for future rational design of optimal drug delivery systems to fight cancer and related diseases.