| 项目编号: | 1511562
|
| 项目名称: | UNS: COLLABORATIVE RESEARCH: Study of Amyloid Protein Oligomerization Using Microchannel Electrophoresis |
| 作者: | Melissa Moss
|
| 承担单位: | University of South Carolina at Columbia
|
| 批准年: | 2014
|
| 开始日期: | 2015-07-01
|
| 结束日期: | 2018-06-30
|
| 资助金额: | USD300000
|
| 资助来源: | US-NSF
|
| 项目类别: | Standard Grant
|
| 国家: | US
|
| 语种: | 英语
|
| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
|
| 英文关键词: | protein aggregation
; amyloid-beta
; protein
; protein amino acid sequence
; biofouling
; disease
; time-dependent study
; amyloid behavior
; protein flexibility
; custom microchannel electrophoresis
; amyloid structure
; amyloid protein oligomerization
; competitive research
; model protein
; collaborative undergraduate research exchange
; me
; protein aggregate
; pathogenic protein
; materials research
; amyloid protein
|
| 英文摘要: | 1511562/1511876
Moss/Hestekin
The aggregation of amyloid proteins is involved in a wide range of processes including the pathogenesis of numerous diseases (Alzheimer's disease, type 2 diabetes, etc.) as well as in biofouling associated with applications such as food production or water purification. A better understanding of the aggregation process will not only help to prevent unwanted protein aggregation, but may also be used to design small-scale manufacturing processes where molecules are able to assemble in an ordered and repeatable fashion, such as in the production of nanowires for electronics. The goal of this project is to discover the primary mechanism involved in the initiation of protein aggregation by examining proteins involved in diseases and biofouling. In order to understand this mechanism, key properties of the proteins will be altered in a controlled manner and their effect on protein aggregation will be explored using methods that analyze aggregate size and structure. In addition, changes in amyloid behavior in the presence of inhibitor molecules will be examined. By advancing our understanding of these early stages of protein aggregation, we will be able to design better drugs for treating debilitating diseases, reduce unwanted biofouling, and facilitate industrial applications.
The proposed work employs a custom Microchannel Electrophoresis (ME) system that utilizes a blended polymer matrix to facilitate separation of individual oligomer populations that span a wide range of molecular weights. Three model proteins will be studied: amyloid-beta, involved in the pathogenesis of Alzheimer's disease, amylin, a pathogenic protein in type 2 diabetes, and chaplin H, a protein critical for biofouling. ME will be employed to elucidate the effect of protein amino acid sequence, including the length of hydrophobic stretches and protein flexibility, on the evolution of oligomeric aggregates. In addition, ME will be employed to investigate the ability of eight known small molecule inhibitors of aggregation to modulate oligomer formation. Oligomer size determination as well as binding of florescent dyes that recognize hydrophobic domains and amyloid structure will be coupled with time-dependent studies to define the conformation, size, time to appearance, and relative quantity of oligomers formed. The custom ME's dual optical detection capabilities will be exploited to simultaneously detect oligomers via UV and bound fluorescent dyes. The advancement in understanding the influences of protein amino acid sequence and small molecule inhibitors on amyloid protein oligomerization will define new directions for the inhibition and manipulation of protein aggregation with applications in drug development, pharmaceutical production, biofouling, and nanotechnology. The experimental work will be integrated with biomedical engineering education. Specifically, the proposed work will establish a collaborative undergraduate research exchange for six undergraduate students and will develop a design based module to be distribution to high school and middle school teachers that familiarizes precollege students with the concepts of protein aggregation and separation of protein aggregates.
This award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Biomaterials Program of the Division of Materials Research and by the Experimental Program to Stimulate Competitive Research (EPSCoR). |
| 资源类型: | 项目
|
| 标识符: | http://119.78.100.158/handle/2HF3EXSE/94277
|
| Appears in Collections: | 影响、适应和脆弱性
气候减缓与适应
|
|
There are no files associated with this item.
|
| Recommended Citation: | |
Melissa Moss. UNS: COLLABORATIVE RESEARCH: Study of Amyloid Protein Oligomerization Using Microchannel Electrophoresis. 2014-01-01.
|
|
|