Acquisition of Research Insrumentation for Molecular and Cellular Biology

获得分子和细胞生物学研究仪器

• 批准号: 0115944
• 负责人: Steven James
• 金额: $ 9.78万
• 依托单位: Gettysburg College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0115944&HistoricalAwards=false
• 关键词: Acquisition; Research; Insrumentation; Molecular; Cellular

A grant has been awarded to Dr. Steven James and Dr. Kazuo Hiraizumi, co-principal investigators at Gettysburg College, to procure two major items of equipment through the Major Research Instrumentation Program of the NSF. A computerized system that integrates photodocumentation with image analysis and a preparative ultracentrifuge will allow the two faculty and their students to conduct research that cannot be executed with the equipment currently available at Gettysburg College. The goals of this grant are to expand the scope and quality of training in molecular and cellular biology for undergraduates. Gettysburg College provides a research-intensive learning environment for undergraduates in the sciences. Experiential, hands-on learning is encouraged by requiring student-faculty collaborative research for the B.S. degrees in Biology and Biochemistry/Molecular Biology (BMB). Students in these degree programs write a research prospectus, spend at least a full semester on their research, write a scientific paper on their work that is evaluated by faculty, and present their research to their peers during an end-of-semester colloquium. All BMB majors are required to conduct individualized research and over 60% of Biology majors choose the B.S. track; a substantial number of these students go on to graduate school. The instrumentation procured with NSF support will allow undergraduates working with Drs. James and Hiraizumi to perform cutting-edge research, thereby giving them excellent preparation for graduate school and careers in science. The focus of Dr. James' research is the regulation of the cell cycle, a carefully orchestrated series of events that coordinates chromosome replication with nuclear and cell division. Dr. James studies the role of genes that regulate this process, using as a model system the bread mold Aspergillus. The focus of Dr. Hiraizumi's research is population and evolutionary genetics of gene regulation. He studies genes that code for a group of digestive enzymes called peptidases, using the fruit fly Drosophila melanogaster. Both faculty employ techniques of molecular genetics, cell biology, and biochemistry in their research. In these fields, a most fundamental question involves the relationship between the DNA sequence of a gene and the function of the protein that it encodes. Mutations in the sequence of DNA often cripple or destroy the resulting protein, which can produce devastating effects. To understand the relationship between DNA sequence, protein function, and the physiological effects of mutations requires sophisticated instrumentation for isolating molecules and measuring their activity. First, the ultracentrifuge provided by support from this NSF-MRI grant will enable isolation of large amounts of maximally pure DNA and protein. This preparative ultracentrifuge subjects particles or molecules to high centrifugal force and separates them based on differences in their density, size or shape. Second, the photodocumentation /image analysis system will be used to measure the activity of both normal and mutant proteins. These proteins will be isolated and purified using the ultracentrifuge, or by a different technique called gel electrophoresis. Gel electrophoresis separates molecules through a gel matrix subjected to electrical current. DNA can also be separated in this manner. To detect and measure the molecules of interest, they are chemically stained or radioactively labeled. The resulting signals are stored as electronic files, which can be analyzed for quantitative differences with a high degree of sensitivity and precision. This helps to determine which genes are turned on under various conditions, how much of the protein is present, and whether there are differences in the activity of a protein between genetically different individuals. The research conducted by these faculty and their students addresses questions that have potential medical applications. For example, many genes that regulate cell division can undergo mutation that leads to cancer. In all organisms, cell division is governed by a similar set of genes. Thus, investigating the regulation of genes that control cell division in a simple, easy-to-study model organism such as Aspergillus aids in understanding the molecular and cellular processes leading to cancer in more complex, less tractable organisms such as humans. Recently, scientists discovered surprising similarity in the DNA sequence of human and fruit fly genes. A mutation in a peptidase-coding gene could produce debilitating effects, such as a form of neuronal ceroid lipofuscinosis, a fatal hereditary neurodegenerative disease in humans. The use of the fruit fly peptidases as a model provides information on how mutations affect the physiological function of these enzymes in other organisms, including humans. Thus, with support from the NSF-MRI grant, Gettysburg College undergraduates will benefit from expanded opportunities to perform modern research on relevant biological problems. These experiences will in turn prepare them for graduate studies in molecular and cellular biology and careers in biomedical research.

葛底斯堡学院的联合首席研究员Steven James博士和Kazuo Hiraizumi博士获得了一笔赠款，用于通过NSF的主要研究仪器计划采购两项主要设备。一个集照片记录和图像分析于一体的计算机化系统，以及一个预备性的超离心机，将允许两名教职员工和他们的学生进行目前葛底斯堡学院现有设备无法进行的研究。这项资助的目标是扩大本科生在分子和细胞生物学方面的培训范围和质量。葛底斯堡学院为理科本科生提供了一个研究密集的学习环境。生物和生物化学/分子生物学(BMB)学士学位要求师生合作研究，鼓励体验式动手学习。这些学位课程的学生写一份研究说明书，至少花一个学期的时间在他们的研究上，写一篇关于他们的工作的科学论文，由教员评估，并在学期末的座谈会上向他们的同龄人展示他们的研究。所有BMB专业的学生都被要求进行个性化研究，超过60%的生物专业学生选择了理工科；其中相当一部分学生继续读研究生。在NSF的支持下获得的仪器将允许本科生与詹姆斯博士和平泉博士一起进行尖端研究，从而为他们进入研究生院和从事科学职业做好准备。詹姆斯博士的研究重点是细胞周期的调控，这是一系列精心策划的事件，协调了染色体复制与核和细胞分裂。詹姆斯博士以面包霉菌曲霉为模型系统，研究了调控这一过程的基因的作用。平泉博士的研究重点是基因调控的种群和进化遗传学。他使用果蝇黑腹果蝇研究了一组消化酶的编码基因，这种酶被称为多肽酶。这两个学院在他们的研究中使用了分子遗传学、细胞生物学和生物化学的技术。在这些领域中，一个最基本的问题涉及到基因的DNA序列和它编码的蛋白质功能之间的关系。DNA序列的突变通常会削弱或破坏所产生的蛋白质，这可能会产生毁灭性的影响。要了解DNA序列、蛋白质功能和突变的生理效应之间的关系，需要复杂的仪器来分离分子并测量它们的活性。首先，由NSF-MRI赠款支持提供的超速离心机将能够分离出大量最纯的DNA和蛋白质。这种制备性超速离心机使颗粒或分子受到高离心力，并根据它们的密度、大小或形状的不同将它们分离。其次，将使用照相文件/图像分析系统来测量正常和突变蛋白质的活性。这些蛋白质将使用超速离心法或另一种称为凝胶电泳法的技术进行分离和纯化。凝胶电泳通过受到电流作用的凝胶基质来分离分子。DNA也可以用这种方式分离。为了检测和测量感兴趣的分子，它们被化学染色或放射性标记。产生的信号以电子文件的形式存储，可以高度灵敏和精确地分析量化差异。这有助于确定哪些基因在不同条件下被激活，存在多少蛋白质，以及基因不同的个体之间蛋白质的活性是否存在差异。这项由这些教师和他们的学生进行的研究解决了具有潜在医学应用的问题。例如，许多调节细胞分裂的基因可能会发生突变，导致癌症。在所有生物体中，细胞分裂都是由一组相似的基因控制的。因此，研究控制细胞分裂的基因在简单、易于研究的模式生物体(如曲霉)中的调节有助于理解在更复杂、更难处理的生物体(如人类)中导致癌症的分子和细胞过程。最近，科学家们发现人类和果蝇基因的DNA序列惊人地相似。肽酶编码基因的突变可能会产生衰弱效应，例如一种形式的神经元蜡样脂褐素沉着症，这是一种人类致命的遗传性神经退行性疾病。使用果蝇多肽酶作为模型，提供了突变如何影响包括人类在内的其他生物体中这些酶的生理功能的信息。因此，在NSF-MRI赠款的支持下，葛底斯堡学院的本科生将受益于更多的机会对相关生物学问题进行现代研究。这些经历将反过来为他们在分子和细胞生物学的研究生学习和生物医学研究的职业生涯做好准备。