Molecular Analysis of Disease Pathways

描述（由申请人提供）：开发新的使能技术对于提高我们对疾病的理解和治疗至关重要。免疫测定、基因测序和质谱分析是通过识别生物标志物和疾病途径而使生物医学研究发生革命性变化的技术实例。我们在此提议建立一个新的COBRE中心，专注于疾病途径的分子分析。该中心将汇集来自堪萨斯大学和其他学术机构的物理、生物和制药科学的初级和高级教师，开展多学科研究，开发和实施尖端技术，以阐明与疾病有关的生物过程的遗传、化学和物理机制。该中心的科学重点将是创造和实施新的使能技术，以识别治疗靶点。这些使能的方法包括将下一代基因测序与模式生物的遗传操作相结合的方法，用于监测体内模式生物生理/病理过程的定制合成荧光分子探针，以及用于操纵模式生物和监测体内生化途径的微流体系统。该提案的一个关键创新要素是创建三个核心设施，旨在协同运作：使用一个核心设施开发的荧光探针处理的模式生物成像将通过使用第二个核心设施开发的微制造设备而得到便利；针对这些探针筛选秀丽隐杆线虫和斑马鱼等突变生物将用于发现新的疾病相关表型，这些表型可以通过下一代基因组测序和第三个核心设施提供的相关基因组技术精确定位，以确定特定靶标。该中心将发挥堪萨斯大学的优势

DESCRIPTION (provided by applicant): The development of new enabling technologies is critical to improving our understanding and treatment of disease. Immunoassays, gene sequencing, and mass spectrometry represent examples of technologies that have revolutionized biomedical research by allowing the identification of biomarkers and disease pathways that could not have been discovered otherwise. We propose here a new COBRE center focused on Molecular Analysis of Disease Pathways. This Center will bring together junior and senior faculty from the physical, biological, and pharmaceutical sciences at the University of Kansas and other academic institutions in Kansas to conduct multidisciplinary research to develop and implement cutting-edge technologies for elucidating the genetic, chemical, and physical mechanisms of biological processes involved in disease. The scientific emphasis ofthe Center will be to create and implement new enabling technologies for identification of therapeutic targets. These enabling methodologies include methods for integrating next generation gene sequencing with genetic manipulation of model organisms, custom-synthesized fluorescent molecular probes for monitoring physiological/pathological processes in model organisms in vivo, and microfluidic systems for manipulation of model organisms and monitoring of biochemical pathways in vivo. A key innovative element of this proposal is the creation of three core facilities that are designed to operate synergistically: imaging of model organisms treated with fluorescent probes developed by one core facility will be facilitated by the use of microfabricated devices developed in a second core facility; screening of mutant organisms such as C. elegans and zebrafish against these probes will be used to discover novel disease-related phenotypes that can be precisely mapped to identify specific targets through the next generation genomic sequencing and related genomic technologies offered by a third core facility. The proposed Center will exploit the strengths of KU and associated universities in the areas of genetics, bioanalytical chemistry, bioengineering, and chemical synthesis and will create new methodologies and approaches that can be used to investigate any pathway involved in disease. These new technologies will be disseminated through research collaborations, publications, and potential commercialization.