Biomolecular Analysis using Liquid Crystals

使用液晶进行生物分子分析

基本信息

批准号：
7241477
负责人：
NICHOLAS L ABBOTT
金额：
$ 43.33万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-03 至 2009-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7241477
关键词：
Address Agriculture Amplifiers Animal Cancer Model Animal Model Animals Antibodies Antineoplastic Agents Area Basic Cancer Research Basic Science Behavior Binding Biochemical Biochemistry Biological Biological Assay Biological Sciences Biology Biomedical Engineering Biopsy Cancerous Cell Extracts Cells Cellular biology Characteristics Chemicals Chemistry Clinic Clinical Clinical Trials Clinical assessments Companions Comprehensive Cancer Center Cultured Cells Data Development EGF gene EGFR Protein Overexpression End Point Engineering Ensure Epidermal Growth Factor Receptor Evaluation Event Exhibits Faculty Family Family Felidae Felis catus Fluorescence Foundations Future Goals Human Image Immobilization Immunoblotting Impact evaluation In Vitro Individual Investigation Laboratory Research Letters Ligation Malignant Neoplasms Malignant neoplasm of lung Mammary gland Measures Mediating Membrane Proteins Methods Molecular Molecular Analysis Molecular Mechanisms of Action Molecular Target Mutation Neoplasms Oncogenic Pan Genus Pathway interactions Peptides Personal Satisfaction Pharmaceutical Preparations Phase Phase I Clinical Trials Phosphotransferases Phosphotyrosine Preparation Principal Investigator Process Prostate Protein Chemistry Protein Tyrosine Kinase Proteins Range Receptor Signaling Regulatory Pathway Reporter Reporting Research Research Personnel Role Sampling Schools Science Screening procedure Signal Transduction Signaling Molecule Signaling Protein Specificity Squamous cell carcinoma Staging Surface System Technology Testing Therapeutic Agents Tissues Tumor Tissue Universities Validation Vision Wisconsin Work Xenograft procedure analytical method analytical tool anti-cancer therapeutic anticancer activity anticancer research base carcinogenesis cell preparation clinically relevant college concept genetic regulatory protein high throughput screening immunocytochemistry in vivo inhibitor/antagonist interfacial liquid crystal medical schools member metaplastic cell transformation method development molecular imaging multidisciplinary mutant nano nanofabrication nanoscale nanostructured novel pancreatic neoplasm programs prototype receptor receptor expression size success tool tool development

项目摘要

DESCRIPTION (provided by applicant): The University of Wisconsin Bioengineering Research Partnership (UW-BRP) will focus on the development of new molecular analysis tools that possess the potential to be used to identify and validate biological endpoints whereby the activity of novel anti-cancer agents can be more accurately and rapidly evaluated as to their molecular mechanism(s) and clinical relevance. The work will initially be focused on the analysis of the epidermal growth factor receptor (EGFR), given that its over expression and mutation has been well-associated with some of the most incurable cancers. However, it is anticipated that the principles to be developed will be sufficiently versatile to be applied to other key signaling molecules in the future. Whereas the basis of existing high throughput screens largely restricts their application to in vitro molecular analyses of enriched preparations of receptors or other signaling molecules, the UW-BRP seeks to establish principles for tools that can also be applied to the analysis of samples from cultured cells and from biopsies of xenographs and spontaneous tumor tissues. This capability will ultimately enable a fundamental approach that will span the molecular, cellular and tissue levels and will be used in both basic research and in animal and human clinical trials. In the present proposal, a multidisciplinary team of researchers with diverse expertise in chemical and biological engineering, chemistry and biochemistry, and the biomolecular and biomedical sciences proposes to develop a broadly-applicable bioanalytical approach that integrates advances in the following areas: a) the nano-fabrication of surfaces, b) the development of synthetic and biochemical strategies for the covalent and oriented immobilization of proteins and peptides on surfaces, c) the implementation of liquid crystals as highly sensitive reporters of the presence of proteins captured on surfaces, and d) the investigation of key cell signaling proteins that participate in processes associated with carcinogenesis. Specifically, the analytical characteristics of liquid crystals for reporting the behavior of the well-recognized anti-cancer target, i.e. the EGF receptor, will be compared to conventional analytical methods in a study that will a) rapidly and sensitively assess the levels and activity of wild-type and mutant human EGF receptor in biological samples, b) test the hypothesis that wild-type and oncogenic forms of the EGF receptor exhibit differential inhibitor specificity, and c) assess if agents that potently inhibit EGF-mediated events in vitro will also exhibit a capacity to antagonize EGF receptor expression and/or activity in cell culture. These studies will use the EGF receptor system as a prototype and it is anticipated that the technology will be readily adaptable to a wide range of other molecular targets. In the long term, these new tools should be useful for the assessment of the molecular mechanisms and consequences of anti-cancer agents, thereby facilitating their research from basic biology through to clinical assessment of efficacy.

描述（由申请人提供）：威斯康星大学生物工程研究合作伙伴关系（UW-BRP）将重点介绍新的分子分析工具的开发，这些工具具有用于识别和验证生物学端点的潜力，从而可以更准确地评估新颖的反癌药物的活性，并且可以对其分子机制进行迅速评估。鉴于其过度表达和突变与某些最无法治愈的癌症相关，因此该工作最初将集中在表皮生长因子受体（EGFR）的分析上。但是，预计将来要制定的原理将足以将其应用于其他关键信号分子。尽管现有的高通量筛选的基础在很大程度上限制了其对富集受体或其他信号分子制剂的体外分子分析的应用，但UW-BRP试图为工具建立原理，这些工具也可以应用于Xen摄影和Xenographmospans和pantanemoste和自发性肿瘤的样品分析的工具。这种能力最终将实现一种基本方法，该方法将跨越分子，细胞和组织水平，并将用于基础研究以及动物和人类临床试验。在本提案中，一个多学科的研究人员团队在化学和生物工程，化学和生物化学方面具有多样化的专业知识，以及生物分子和生物医学科学提议开发一种可广泛适用的生物分析方法，以在以下领域中融合进步，以在以下领域中融合进步：蛋白质和肽的定向固定在表面上，c）液晶的实施，作为在表面上捕获的蛋白质存在的高度敏感记者，d）研究参与与癌变相关的过程的关键细胞信号蛋白的研究。具体而言，将在一项研究中将液晶的分析特性与传统的分析方法进行比较，即EGF受体，即EGF受体，在一项研究中，将a）快速，敏感地评估生物学样本中野生型和突变的人类EGF受体的水平和活性。差异抑制剂特异性，c）评估在体外抑制EGF介导的事件的药物是否还将表现出与细胞培养中EGF受体表达和/或活性对抗的能力。这些研究将使用EGF受体系统作为原型，预计该技术将很容易适应其他分子靶标。从长远来看，这些新工具应有助于评估抗癌剂的分子机制和后果，从而促进其从基本生物学到疗效临床评估的研究。