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Precipitation and Self-Interaction of Viruses by Preferential Hydration

病毒通过优先水合的沉淀和自相互作用

基本信息

批准号：
1159425
负责人：
Caryn Heldt
金额：
$ 24.77万
依托单位：
Michigan Technological University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-15 至 2017-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1159425&HistoricalAwards=false
关键词：
Precipitation Self Interaction Viruses Preferential

项目摘要

1159425HeldtThe objective of this research is use high-throughput methods to understand the principles behind selective precipitation of viruses with osmolytes to create a universal purification method for viruses that uses measured values of virus self-interaction based on theoretical and not empirically derived correlations. Our hypothesis is that osmolytes will preferentially precipitate viruses due to preferential hydration (the selective partitioning of water around a solute molecule) and result in the aggregation of viruses due to hydrophobic interactions. Both enveloped and non-enveloped viruses will be examined to understand the differences in these viruses classes. This is a transformative method to approach virus removal. Most virus removal is done empirically, whereas in this proposal, we will quantify selfinteraction parameters that will guide future methods for virus purification, removal and detection. This will be accomplished through the completion of the project goals. Goal 1: Use high-throughput screening to discover precipitants that selectively precipitate an enveloped and non-enveloped virus. High-throughput screening in 96-well plates will allow quick evaluation of multiple precipitants and precipitation condition. Goal 2: Quantify the thermodynamics of viruses in contact with precipitants. Close examination of flocculent size and solubility of viruses with co-solvents will allow an in depth evaluation of virus self-interaction and virus hydrophobicity. Goal 3: Expand the virus range to determine if the precipitants can be used as a platform approach to virus precipitation. Two additional viruses will be examined to determine if precipitation conditions are universally applicable to multiple viruses. The proposed activities will also strengthen the research, education, and outreach at Michigan Tech, the local Great Lakes region, and throughout the world. The need to develop a platform approach to virus purification will increase the speed to market of new vaccines and this purification can also be applied to viral gene therapy vectors. This proposal will use osmolytes to probe the self-interaction of enveloped and non-enveloped viruses. The implications of this knowledge will far extend from the precipitation of viruses to expand the toolbox of any virus separation or detection method to allow a more theoretically based approach to the design of the technique. The included education plan will introduce students from primary education up to graduate students to the STEM fields and the need to understand virus interactions to create improved virus removal, purification, and sensing technologies. Participation in Summer Youth Programs (SYP) and the Western U.P. Science Fair will attract underrepresented and economically disadvantaged groups and bring them to Michigan Tech to experience hands-on science and engineering programs and encourage them to pursue a career in a STEM fields.

1159425Heldt本研究的目标是使用高通量方法来了解用渗透分子选择性沉淀病毒背后的原理，以创建一种通用的病毒纯化方法，该方法使用基于理论而不是经验推导的相关性的病毒自身相互作用的测量值。我们的假设是，由于优先水化作用(水在溶质分子周围的选择性分配)，渗透分子将优先沉淀病毒，并由于疏水相互作用导致病毒聚集。将检查包膜病毒和非包膜病毒，以了解这些病毒类别的差异。这是一种变革性的病毒清除方法。大多数病毒的去除都是经验性的，而在这项提议中，我们将量化自我相互作用参数，这些参数将指导未来的病毒纯化、去除和检测方法。这将通过完成项目目标来实现。目标1：使用高通量筛查来发现选择性地沉淀包膜和非包膜病毒的沉淀剂。96孔板的高通量筛选将允许快速评估多个沉淀剂和沉淀条件。目标2：量化与沉淀剂接触的病毒的热力学。仔细检查病毒的絮凝体大小和与共溶剂的溶解性，将有助于深入评估病毒的自身相互作用和病毒的疏水性。目标3：扩大病毒范围，以确定沉淀剂是否可用作病毒沉淀的平台方法。将检查另外两种病毒，以确定降水条件是否普遍适用于多种病毒。拟议的活动还将加强密歇根理工大学、当地五大湖区和世界各地的研究、教育和推广。需要开发一种平台方法来提纯病毒，这将加快新疫苗上市的速度，这种提纯也可以应用于病毒基因治疗载体。这项提议将使用渗透分子来探测包膜和非包膜病毒的自我相互作用。这一知识的影响将远远超出病毒的沉淀，以扩展任何病毒分离或检测方法的工具箱，以允许更基于理论的方法来设计该技术。包括的教育计划将向从小学到研究生的学生介绍STEM领域，以及了解病毒相互作用的必要性，以创造改进的病毒去除、纯化和传感技术。参加夏季青年计划(SYP)和西部大学科学博览会将吸引代表不足和经济困难的群体，并将他们带到密歇根理工大学体验实践科学和工程项目，并鼓励他们在STEM领域追求职业生涯。