CORE--TISSUE BANK AND ANTIBODY

许多关于控制细胞生长和发育的信号转导机制的基本见解来自于对遗传简单的儿科肿瘤的分析。通过DFCI/儿童医院的联合雨肿瘤临床，我们的项目可以特别获得罕见的神经外胚层起源的儿科肿瘤。这种原始神经外胚层肿瘤可以被概念化为多能神经祖细胞发育停滞。一些较大的儿科医院和儿科脑肿瘤联盟已经建立了PNET银行。然而，这些库中的组织样本通常对分子生物学家没有用处，因为没有努力保存信息mRNA和磷蛋白。在Scott Pomeroy博士的指导下，我们已经开始以一种对分子生物学研究人员有用的形式储存PNIPs和其他罕见的儿童实体瘤。在手术室中将肿瘤在液氮中快速冷冻，以将mRNA保存为酪氨酸磷蛋白。还收集了患者的血液样本以及家族史。忽视这一重要的临床资源是不负责任的，尤其是当我们提出的研究可能对DFCI/儿童医院的儿科患者有实际意义时。因此，我们请求将这一设施作为核心资源予以支持。随着时间的推移，随着研究的进展，惠特曼和格林伯格博士几乎肯定会想在这些“信息丰富”的儿科组织样本中探索FAST和BAD同系物的功能。合成的磷酸肽可用于产生抗体，所述抗体报告在特定生长因子受体或信号产生蛋白内的限定位置处的酪氨酸、丝氨酸或苏氨酸的磷酸化状态。磷酸肽导向抗体可以靶向几乎任何生长因子受体或由磷酸化调节的信号传导产生蛋白。这些抗体比常规抗体具有更高的选择性。 因此，它们有助于研究复杂动物组织如脑中的受体活化。有些人将需要这样的抗体靶向蛋白质，如SMAD，BAD，PDGF受体和Trks。核心设施可以实现规模经济。

Many fundamental insights into signal transduction mechanisms that control cell growth and development have come via analysis of genetically simple, pediatric tumors. Via the joint rain tumor clinical at DFCI/Children's Hospitals, our program has exceptional access to rare pediatric tumors of neural ectodermal origin. This primitive neural ectodermal tumors can be conceptualized as multi-potent neural progenitor cells are developmentally stalled. Some of the larger pediatric hospitals and pediatric brain tumor consortiums have established PNET banks. However the tissue samples in these banks are, in general of no use to molecular biologists because no effort has been made to preserve information mRNAs and phosphoproteins. Under the direction of Dr. Scott Pomeroy, we have begun to bank PNETs and other rare solid tumors of childhood in a format that is of use to molecular biology researchers. Tumors are snap frozen in liquid nitrogen in the operating room so as to preserve mRNA to tyrosine phosphoprotein. Patient blood samples are also collected, together with family histories. It would be irresponsible to ignore this important clinical resource as a route to discovery-especially when the studies we propose could have practical overtones for the pediatric patients at DFCI/Children's Hospitals. According we request support for this facility as a core resource. Over time, as the research progresses, Drs. Whitman and Greenberg will almost certainly want to explore the function of FAST and BAD homologues in these "informative" pediatric tissue samples. Synthetic phosphopeptides can be used to raise antibodies that report the phosphorylation state of tyrosine, serine or threonine at defined positions within a specific growth factor receptor or signaling generating protein. Phosphopeptide-directed antibodies can be targeted to virtually any growth factor receptor or signaling generating protein which is regulated by phosphorylation. These antibodies are considerably more selective than conventional antibodies. Thus they lend themselves to studies on receptor activation in complex animal tissues such as brain. Some will need of such antibodies targeted to proteins such as SMADs, BADs, PDGF receptors and Trks. Economies of scale can be achieved with a core facility.