| 项目编号: | 1705923
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| 项目名称: | Engineering a new family of consensus repeat proteins based on nucleoporins |
| 作者: | Bradley Olsen
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| 承担单位: | Massachusetts Institute of Technology
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| 批准年: | 2017
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| 开始日期: | 2017-09-01
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| 结束日期: | 2020-08-31
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| 资助金额: | 350000
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| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
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| 英文关键词: | protein
; numerous minimal consensus repeat
; protein binding energy
; natural nucleoporin
; human nucleoporin
; biochemical engineering program
; modular protein design
; biomimetic tissue engineering matrix
; yeast nucleoporin
; mcr
; full recombinant protein
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| 英文摘要: | Inside all of our cells, DNA is protected by a barrier that allows certain necessary molecules to pass through pores that open and close to regulate passage. Recently, these protein pores have been produced in bacteria, where they retain the same ability to regulate the passage of molecules. To understand how the pores operate, examples of these will be taken from several different types of cells and compared and contrasted. Once the operating principles are identified, these pores will be engineered help purify new biological drugs, remove toxins from liquid samples, and possibly even develop tests to estimate how quickly drugs are taken up in the body. Outreach to a diverse community is accomplished through participation of the PI in the ACCESS Program to promote URM graduate study, and the CMSE community college research program to provide summer research experiences to community college students. Research will be integrated into new teaching materials through international outreach and teaching exchanges with UNICAMP in Brazil. Teaching materials will be prepared in digital form, including online videos, in multiple languages for U.S. and Latin American communities.
Numerous minimal consensus repeat (MCR) sequences from proteins have been identified, leading to modular protein design and advances in technologies such as stimuli-responsive drug delivery materials and biomimetic tissue engineering matrices. Recently, a MCR has been derived from yeast nucleoporin, a protein that regulates transport into and out of the nucleus. When polymerized into a gel, this MCR exhibits the high rate and high selectivity filtration of the natural nucleoporin. Rational design will be used to explore mutations to understand function and modify the selectivity of the protein. The physical properties (diffusion, solubility, and protein binding energies) of mutants will be characterized, and transport and barrier properties will be benchmarked against full recombinant proteins using quantitative transport models. MCR sequences will also be extracted from human nucleoporins to explore the breadth of sequence space that can lead to selective transport properties and provide human-similar in vitro tools for modeling nuclear transport.
This project is supported by the Cellular and Biochemical Engineering Program in the Chemical, Bioengineering and Transport Division with cofounding from the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/89096
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| Appears in Collections: | 全球变化的国际研究计划
科学计划与规划
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| Recommended Citation: | |
Bradley Olsen. Engineering a new family of consensus repeat proteins based on nucleoporins. 2017-01-01.
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