CORE--TISSUE BANK AND ANTIBODY

对控制细胞生长和发育的信号转导机制的许多基本见解都是通过对基因简单的儿科肿瘤的分析得出的。通过DFCI/儿童医院的联合肿瘤临床，我们的项目获得了罕见的神经外胚层来源的儿童肿瘤。这种原始神经外胚层肿瘤可以被定义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协会已经建立了PNET库。然而，这些组织样本库通常对分子生物学家没有用处，因为没有努力保存信息mrna和磷酸化蛋白。在Scott Pomeroy博士的指导下，我们已经开始将PNETs和其他罕见的儿童实体瘤以一种可供分子生物学研究人员使用的形式储存起来。肿瘤在手术室用液氮快速冷冻，以保存酪氨酸磷酸化蛋白mRNA。还收集了患者的血液样本和家族史。忽视这一重要的临床资源作为发现途径是不负责任的，尤其是当我们提出的研究可能对DFCI/儿童医院的儿科患者具有实际意义时。因此，我们请求支持这一设施作为核心资源。随着时间的推移，随着研究的进展。惠特曼和格林伯格几乎肯定会想要在这些“信息丰富”的儿科组织样本中探索FAST和BAD同源物的功能。合成的磷酸肽可用于培养抗体，这些抗体报告特定生长因子受体或信号生成蛋白中特定位置的酪氨酸、丝氨酸或苏氨酸的磷酸化状态。磷酸肽定向抗体可以针对几乎任何生长因子受体或信号产生蛋白，这是由磷酸化调节。这些抗体比传统抗体更具选择性。因此，它们有助于研究复杂动物组织（如大脑）中的受体激活。有些人将需要这种针对蛋白质的抗体，如SMADs、BADs、PDGF受体和Trks。规模经济可以通过核心设施来实现。

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.