MRI: Acquisition: MALDI-TOF/TOF Mass Spectrometer for Multidisciplinary Research and Teaching at an Undergraduate College for Women

在Vardar-Ulu博士的指导下，韦尔斯利学院获得了一笔赠款，用于购买Bruker Daltonics Autoflex Fast MALDI/TOF质谱仪，该质谱仪具有MS/MS多肽测序、MALDI成像和用于小分子分析的无基质靶标，用于本科学院的跨学科研究。质谱仪是一种可以非常准确地确定完整蛋白质、蛋白质片段(多肽)甚至它们的组成成分(氨基酸)的质量的仪器。在过去的十年里，质谱学已经成为生物学家、生物化学家和化学家研究大分子的结构和功能特征的首选方法。自从2003年收购了第一台全能MALDI-TOF质谱仪(也是通过NSF-MRI计划获得的)以来，质谱学已经成为卫尔斯理学院许多教职员工研究计划中的一个关键元素，并推动了该学院多门课程基于发现的教学实验室的发展。然而，这个仪器现在已经是一个停产的平台，已经不能满足目前教职员工的研究和培训需求。这一新仪器不仅将增强现有的研究能力，还将为这一快速发展领域的新研究提供额外的能力。这个项目的目标是让来自学院内外几个系的本科生和教职员工共同努力，解决生物、化学和神经科学中的重要研究问题。如下所述，所述项目的范围非常不同，将利用这一文书的许多新特点及其常规用途。几个项目涉及其基因组已经解决的生物体，并将使用MALDI-TOF在相互作用的复合体中识别新的蛋白质，而其他项目将受益于该仪器提供的额外新功能，如蛋白质测序和MALDI成像。项目1(化学)将使用MS从关键信号分子(Notch蛋白)的潜在自解中确定确切的切割位点，而项目2(生物学)将验证酿酒酵母蛋白质中的磷酸化位点，这些位点特别需要细胞质有丝分裂周期蛋白进行磷酸化。项目3(生物学)、项目5(化学)、项目7(神经科学)将使用MS分别鉴定与拟南芥叶片中蓝光受体PHOT1和PHOT2相互作用的蛋白质、组蛋白衍生抗菌肽的细胞内靶标以及雌性小鼠脑中类固醇受体复合体中的新蛋白质。项目4(生物学)将使用新的MALDI成像功能来成像昆虫的内部组织，而项目6(化学和生物)将使用它来演示使用金纳米颗粒(AuNPs)作为生物医学研究的靶向载体的可行性。还制定了具体计划，通过以发现为基础的蛋白质组学实验室，以及在有机化学和生物化学中，加强该仪器在中级和高级本科实验室中的课程使用。这些项目的科学价值及其对女本科生教学和研究培训的关注，直接说明了这一建议的智力价值。卫尔斯理在女科学家教育方面的卓有成效的记录，以及它最近在吸引更多代表不足的少数群体进入科学界方面取得的进展，预示着这一工具对研究和培训的持续和广泛影响，并证明它的收购是对下一代科学家的关键投资。鼓励有才华的年轻女性选择科学职业，最终将加强美国科学界的基础设施，并使我们社会的所有成员受益。卫尔斯理学院的主要使命是培养将在世界上有所作为的女性的本科教育。这一承诺在科学界具有特殊的意义，在科学界，妇女的代表性传统上是不足的。生物科学系的14名常任教员、化学系的12名教员和神经科学项目的4名常额教员都对本科生的研究和研究培训保持着高标准，并提供外部资金支持同样专注于培养本科生的生产性研究项目。因此，质谱仪不仅会对科研培训产生影响，还会为我们高比例的教职员工提升科研环境。这些研究工作的结果将通过摘要、评论出版物以及学生和教职员工积极参加专业会议的方式广泛传播。对整个社会的好处将是妇女更多地参与美国科学界，提高人口的科学素养。

A grant has been awarded to Wellesley College under the direction of Dr. Vardar-Ulu to acquire a Bruker Daltonics Autoflex Speed MALDI-TOF/TOF mass spectrometer, with the capability for MS/MS Peptide sequencing, MALDI imaging, and matrix-free targets for small molecule analysis for interdisciplinary research at an undergraduate college. A mass spectrometer is an instrument that can very accurately determine the mass of intact proteins, fragments of proteins (peptides) or even their building blocks (amino acids). In the past ten years, mass spectroscopy has become the method of choice for biologists, biological chemists, and chemists studying the structural and functional features of large molecules. Since the acquisition of the first mass spectrometer Omniflex MALDI-TOF in 2003 (also acquired through the NSF-MRI program), mass spectrometry has become a key element in the research programs of many of the Wellesley College faculty and has been impetus for the development of discovery-based teaching laboratories for several courses at the college. However, this instrument is now a discontinued platform that can no longer meet the current research and training needs of the faculty and students. This new instrument will not only enhance the existing research capabilities, but also provide additional capabilities for new research in this rapidly advancing field. The goal of this project is to allow undergraduate students and faculty from several departments both within and outside the college to engage in collaborative efforts to address important research questions in biology, chemistry, and neuroscience. As summarized below, the described projects are very diverse in their scope and will utilize many of the new features of this instrument as well as its routine uses. Several projects involve organisms whose genomes have been solved and will use the MALDI-TOF to identify novel proteins within interacting complexes, while others will benefit from the additional new capabilities this instrument offers such as protein sequencing and MALDI Imaging. Project 1 (chemistry) will use MS to identify the exact cleavage site from the potential autolysis of a crucial signaling molecule (Notch protein) while Project 2 (Biology) will verify phosphorylation sites within Saccharomyces cerevisiae proteins that specifically require cytoplasmic mitotic cyclins for phosphorylation. Projects 3 (biology), 5 (chemistry), 7 (neuroscience) will use MS to identify proteins that interact with the blue light receptors PHOT1 and PHOT2 in leaves of Arabidopsis thaliana, intracellular targets of histone-derived antimicrobial peptides, and novel proteins in the steroid receptor complex from female mouse brain, respectively. Project 4 (Biology) will use the new MALDI imaging feature to image the internal tissues of insects while project 6 (chemistry and biology) will use it to demonstrate the feasibility of using gold nanoparticles (AuNPs) as targeted vehicles for biomedical research. There are also specific plans to enhance the curricular uses for the instrument in the undergraduate lab settings at both intermediate and advanced levels through a discovery-based laboratory in proteomics, as well as in organic chemistry and biochemistry. The scientific merit of these projects and their focus on the teaching and research training of female undergraduates, speaks directly to the intellectual merit of this proposal. Wellesley's productive record in the education of women scientists, along with its recent progress in attracting more underrepresented minorities to the sciences, bodes well for the sustained and broad impact of this instrumentation on research and training, and justifies its acquisition as a critical investment in the next generation of scientists. The encouragement of talented young women to choose careers in the sciences will ultimately strengthen the infrastructure of the scientific community in the United States and yield benefits to all members of our society. The primary mission at Wellesley College is the undergraduate education of women who will make a difference in the world. This commitment has taken on a special meaning in the sciences where women have traditionally been underrepresented. The permanent faculty of 14 in the Department of Biological Sciences, 12 in Chemistry and 4 in the Neuroscience program maintain high standards for both research and research training for undergraduates with extramural funding supporting productive research programs that also are focused on training undergraduate students. Therefore, the mass spectrometer will not only have an impact on research training, but will also enhance the research environment for a high proportion of our faculty. The results of these research efforts will be broadly disseminated via abstracts, reviewed publications and by active participation of students and faculty at professional meetings. The benefit to society as a whole will be the increased participation of women in the scientific community of the United States and increased scientific literacy in the population.