CORE--TISSUE CULTURE AND MONOCLONAL ANTIBODIES

对导致发育障碍和智力低下相关异常的细胞和分子机制的研究越来越多地通过细胞培养等体外模型系统进行，包括转基因细胞和转基因和基因敲除小鼠的细胞。唐氏综合征或粘多糖症等导致智力低下的疾病的生化病理机制的研究进展，在很大程度上依赖于研究分离细胞培养系统中改变的细胞和生化环境的技术的发展。此外，最先进的发育生物学研究经常需要研究人员开发独特的生物试剂，如多克隆和单克隆抗体，各种类型的核苷酸探针，以及用于将外来基因导入细胞的构建。组织培养/单抗实验室(TCMAC)通过提供核心设施和服务，促进了堪萨斯州MRDDRC研究人员的研究，使他们能够开发、维护和鉴定众多细胞模型系统，以探索正常细胞生长的各个方面，调节细胞活力的信号通路，以及促进或干扰细胞生长的外源因素的影响。TCMAC实验室对该设施在过去的赠款期间所做的许多改进感到非常自豪，因为这些改进使该实验室能够为MRDDRC调查人员提供最高水平的支持。该机构还成功地开发了独特的多克隆和单克隆抗体，满足了个人研究人员的需要。为罗伯特·帕拉佐所做的抗体工作为他识别中心体中的关键蛋白质和监测细胞周期中的变化提供了一个极好的工具。针对Elias Michaelis开发的一系列抗体导致了关于蛋白质表达和定位的重要发现，以应对慢性酒精暴露。该机构在过去的赠款期间开发的抗体目前正被其他大学用于合作研究，一家大公司已表示有兴趣销售一些高度特异和有价值的工具，以便在国际上向科学家提供这些工具。随着TCMAC展望未来和加强中心对生物行为过程的关注的方法，Core将在涉及基因导入、ES细胞生长和生产转基因或基因敲除小鼠所需的其他技术的研究中发挥更大的作用。TCMAC一直是并将继续是一个相对较小的核心，但它在吸引新的高生产率科学家到中心本身，鼓励他们将他们的才华应用于新的高生产率科学家，并鼓励他们运用他们的才华来解决与发育障碍有关的问题方面发挥了极其重要的作用。例如，TCMAC在Rick Dobrowsky、Doug Ruden和Robert Palazzo加入KU教员后不久就吸引他们到MRDDRC发挥了重要作用。随着该大学在分子遗传学、生物信息学和发育神经生物学领域招聘新的教员，这一核心可能会继续发挥这一作用。TCMAC的目标一直是并将继续提供独特的生物试剂、熟练的技术支持和最先进的设备，以促进和加强MRDDRC研究人员的研究，他们研究导致发育障碍的分子事件。TCMAC将通过以下方式继续促进堪萨斯大学的MRDDRC研究：(1)维持一个中央设施，为MRDDRC调查人员购买昂贵的设备和服务提供具有成本效益的替代方案。(2)生产和鉴定独特的单抗/多克隆抗体，并为需要持续供应抗体的项目维持杂交瘤细胞系。

Investigations into the cellular and molecular mechanisms that lead to abnormalities associated with developmental disabilities and mental retardation are increasingly being carried out with in vitro model systems such as cell cultures, including cells transfected with foreign genes and cells derived from transgenic and knockout mice. Advances in understanding the mechanisms for the biochemical pathology of diseases that lead to mental retardation, such as Down syndrome or the mucopolysaccharidoses, have been critically dependent upon the development of techniques for studying the altered cellular and biochemical milieu in isolated cell culture systems. In addition, state-of- the-art research in developmental biology frequently requires that investigators develop unique biological reagents such as polyclonal and monoclonal antibodies, various types of nucleotide probes, and constructs for transfection of foreign genes into cells. The Tissue Culture/Monoclonal Antibodies Laboratory (TCMAC) has facilitated the research of several of the Kansas MRDDRC investigators by providing core facilities and services that enable them to develop, maintain, and characterize numerous cellular model systems for exploring aspects of normal cell growth, signaling pathways that regulate cell viability, and effects of exogenous agents that enhance or disrupt cell growth. The TCMAC Laboratory takes great pride in the many enhancements that have been made in the facility during the past grant period as these improvements enable the lab to provide the highest level of support for MRDDRC investigators. The facility has also successfully developed unique polyclonal and monoclonal antibodies that served the needs of individual investigators. The antibody work done for Robert Palazzo has provided an excellent tool in his efforts to identify critical proteins in the centrosome and monitor changes during the cell cycle. The series of antibodies developed for Elias Michaelis have led to important discoveries regarding protein expression and localization in response to chronic ethanol exposure. Antibodies developed by the facility during the past grant period are currently being utilized at other universities in collaborative studies, and a major company has expressed interested in marketing some of those highly specific and valuable tools so they will be available to scientists on an international level. As the TCMAC looks to the future and means of enhancing the Center's focus on biobehavioral processes, the Core will play an expanding role in studies involving gene transfections, growth of ES cells, and other techniques required to produce transgenic or knockout mice. The TCMAC has been and continues to be a relatively small core, but it has played an extremely important role in attracting new, highly productive scientists to the Center itself and encouraging them to apply their talents to new, highly productive scientists to the Center itself and encouraging them to apply their talents to question related to developmental disabilities. For example, the TCMAC was instrumental in the attracting Rick Dobrowsky, Doug Ruden and Robert Palazzo to the MRDDRC shortly after they joined to KU faculty. This core is likely to continue in this role as the University hires new faculty members in the areas of molecular genetics, bioinformatics and developmental neurobiology. The goal of the TCMAC has been and will continue to be the provision of unique bioreagents, skilled technical support, and state-of-the-art equipment to facilitate and enhance the research of MRDDRC investigators who study molecular events leading to developmental disabilities. The TCMAC will continue to facilitate MRDDRC research at The University of Kansas by: (1) Maintaining a centralized facility that provides a cost-effective alternative to purchase of expensive equipment and services by MRDDRC investigators. (2) Producing and characterizing unique monoclonal/polyclonal antibodies and maintaining hybridoma cell lines for projects requiring a consistent supply of antibodies.