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Development of Nanoscale Neuromodulating Platforms

纳米级神经调节平台的开发

基本信息

批准号：
7916444
负责人：
DAVID R PEPPERBERG
金额：
$ 123.97万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7916444
关键词：
Acetylcholine Affinity Age related macular degeneration Agonist Amino Acid Sequence Amino Acids Baculovirus Expression System Binding Binding Proteins Binding Sites Biochemical Biochemistry Biological Models Biomedical Engineering Biotin Boston Cell Line Cell model Cells Chemical Synapse Chemistry Chicago Complex Computer Simulation Coupled Cysteine Data Degenerative Disorder Deterioration Development Disease Doctor of Philosophy Electrophysiology (science)Engineering Exhibits Extracellular Domain Face Family Functional disorder GABA Receptor Gated Ion Channel Generations Goals Human Illinois In Situ In Vitro Kinetics Laboratories Language Length Ligand Binding Ligands Light Mammalian Cell Mediating Membrane Modeling Molecular Molecular Biology Molecular Genetics Molecular Structure Muscimol N-terminal Neurons Neurosciences Ophthalmology Organic Synthesis Peptide Mapping Peptides Performance Phage Display Pharmaceutical Chemistry Pharmacognosy Pharmacology Phase Phosphinic Acids Photoreceptors Physical Chemistry Physics Physiological Postsynaptic Membrane Preparation Principal Investigator Property Proteins Regulation Relaxation Research Research Personnel Research Project Grants Retina Retinal Retinal Cone Retinal Degeneration Signal Transduction Site Structural Biochemistry Structure Sulfhydryl Compounds System Techniques Technology Testing Time Vertebrate Photoreceptors Visible Radiation Vision Visual Xenopus oocyte analog azobenzene design design and construction extracellular gamma-Aminobutyric Acid in vitro testing nanoscale neurophysiology operation postsynaptic prototype receptor reconstitution research study response retinal neuron transmission process vision science

项目摘要

DESCRIPTION (provided by applicant): Retinal degenerative diseases such as age-related macular degeneration are associated with dysfunction and deterioration of the rod and cone photoreceptors of the retina. Postsynaptic membrane receptor proteins of retinal neurons proximal to the rods and cones mediate the transmission of visual signals at multiple types of chemical synapses in the normally functioning retina, and there is reason to believe that these proximal retinal neurons in certain cases remain functional despite the disease-induced loss of rod and cone visual signaling. The long-term goal of the proposed project is to design and construct nanoscale molecular structures that can selectively attach to the extracellular face of specific membrane receptors of post-photoreceptor retinal neurons and, by modulating the postsynaptic receptor's activity in response to light, restore visual signaling in retina damaged by photoreceptor degenerative disease. In this application we propose a 5-year project aimed at this challenging bioengineering objective. The research will involve closely integrated studies employing molecular biology, organic synthesis, and biophysical/ electrophysiological analysis of prototype systems. A main focus of the proposed experiments is the GABAC receptor, a membrane receptor protein of retinal bipolar cells whose known properties make it well suited as a model system. Leading the research will be David R. Pepperberg, PhD, Principal Investigator (Ophthalmology and Visual Sciences, Univ. of Illinois at Chicago (UIC)); and Co-Investigators Karol S. Bruzik, PhD (Medicinal Chemistry and Pharmacognosy, UIC), Tejal A. Desai, PhD (Biomedical Engineering, Boston Univ.), Jack H. Kaplan, PhD (Biochemistry and Molecular Genetics, UIC), Brian K. Kay, PhD (Biosciences Division, Argonne National Laboratory), Nalin M. Kumar, PhD (Ophthalmology and Visual Sciences, UIC), Guy C. Le Breton, PhD (Pharmacology, UIC), Jie Liang, PhD (Bioengineering, UIC), Haohua Qian, PhD (Ophthalmology and Visual Sciences, UIC), Sandra J. Rosenthal, PhD (Chemistry, Vanderbilt Univ.), and Robert F. Standaert, PhD (Chemistry, UIC). Lay language summary: The project's objective is to develop molecular structures that can restore vision in photoreceptor degenerative diseases such as age-related macular degeneration. These structures will be designed to attach to non-photoreceptor cells of the diseased retina that remain functional and to make these cells responsive to light.

描述（由申请人提供）：视网膜退行性疾病如年龄相关性黄斑变性与视网膜的视杆和视锥光感受器的功能障碍和退化有关。视杆和视锥近端视网膜神经元的突触后膜受体蛋白介导正常功能视网膜中多种类型化学突触处的视觉信号的传递，并且有理由相信，尽管疾病诱导的视杆和视锥视觉信号的丧失，但这些近端视网膜神经元在某些情况下仍保持功能。该项目的长期目标是设计和构建纳米级分子结构，该结构可以选择性地附着到感光后视网膜神经元的特定膜受体的细胞外表面，并通过调节突触后受体对光的反应活性，恢复感光变性疾病损伤的视网膜中的视觉信号。在这个应用程序中，我们提出了一个为期5年的项目，旨在实现这一具有挑战性的生物工程目标。该研究将涉及采用分子生物学，有机合成和原型系统的生物物理/电生理分析的紧密结合的研究。所提出的实验的一个主要焦点是GABAC受体，视网膜双极细胞的膜受体蛋白，其已知的特性使其非常适合作为模型系统。领导这项研究的将是大卫R。Pepperberg博士，主要研究者（眼科和视觉科学，伊利诺伊大学芝加哥分校（UIC））;和共同研究者Karol S. Bruzik，PhD（药物化学和生药学，UIC），Tejal A. Desai博士（波士顿大学生物医学工程），Jack H. Kaplan博士（生物化学和分子遗传学，UIC），Brian K. Kay，PhD（生物科学部，阿贡国家实验室），Nalin M. Kumar，PhD（Ophthalmology and Visual Sciences，UIC），Guy C. Le布雷东博士（药理学，UIC），Jie Liang博士（生物工程，UIC），Haohua Qian博士（眼科和视觉科学，UIC），Sandra J. Rosenthal博士（化学，范德比尔特大学），和Robert F. Standaert，PhD（Chemistry，UIC）. Lay language总结：该项目的目标是开发可以恢复感光细胞退行性疾病（如年龄相关性黄斑变性）视力的分子结构。这些结构将被设计成附着在患病视网膜的非感光细胞上，这些细胞保持功能，并使这些细胞对光有反应。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mapping protein interactions by combining antibody affinity maturation and mass spectrometry.

DOI：
10.1016/j.ab.2011.05.005
发表时间：
2011-10-01
期刊：
Analytical biochemistry
影响因子：
2.9
作者：
Dyson MR;Zheng Y;Zhang C;Colwill K;Pershad K;Kay BK;Pawson T;McCafferty J
通讯作者：
McCafferty J

Generating a panel of highly specific antibodies to 20 human SH2 domains by phage display.

DOI：
10.1093/protein/gzq003
发表时间：
2010-04
期刊：
Protein engineering, design & selection : PEDS
影响因子：
0
作者：
Pershad K;Pavlovic JD;Gräslund S;Nilsson P;Colwill K;Karatt-Vellatt A;Schofield DJ;Dyson MR;Pawson T;Kay BK;McCafferty J
通讯作者：
McCafferty J

Apparent structural differences at the tetramerization region of erythroid and nonerythroid beta spectrin as discriminated by phage displayed scFvs.

通过噬菌体展示的 scFv 可以区分红系和非红系 β 血影蛋白四聚化区域的明显结构差异。