GENE STRUCTURE, ARRANGEMENT, DYNAMICS, AND EXPRESSION

该计划的目标是发展新的物理化学 解决细胞和分子中以前难以解决的问题的技术 生物学。一半以上的努力将致力于完善 脉冲梯度凝胶电泳法及其高灵敏度的研究进展 切割DNA分子的特殊方法。将这些技术结合起来 将允许快速绘制人类基因图谱，并对各种 染色体重排，包括基因重排和与 致癌转化。该计划的一部分将集中在 肿瘤病毒微染色体和In中染色质的拓扑性质 整个哺乳动物的染色体。其目的是了解染色质是如何 基因表达过程中的结构和能量学变化以及 DNA的刚性用于正常和异常的基因调控。另一个 该计划的一部分涉及通过以下方式使大分子内化 淋巴细胞。其中一个目标是研究特定的淋巴细胞如何能够 使特定的组织相容性抗原内化。另一个目标 是开发利用淋巴细胞内化来传递的系统 可光激活药物治疗恶性淋巴细胞症。最后，在两个非常 将开发投机项目技术，以探索 RNA拓扑异构体的存在和其他技术将发展到 生物合成产生荧光标记的蛋白质。

The goal of this program is the development of new physical and chemical techniques to solve previously intractable problems in cell and molecular biology. More than half the effort will be devoted to the refinement of pulsed field gradient gel electrophoresis and the development of highly specific methods for cleaving DNA molecules. Together these techniques will allow rapid mapping of human genes, and molecular analysis of various chromosome rearrangements including genes and rearrangements linked to oncogenic transformation. Part of the program will focus on the topological properties of chromatin in tumor virus minichromosomes and in whole mammalian chromosomes. The object is to understand how chromatin structure and energetics change during gene expression and how the stiffness of DNA is used in normal and abnormal gene regulation. Another part of the program deals with the internalization of macromolecules by lymphocytes. One objective is to study how particular lymphocytes are able to internalize particular histocompatibility antigens. Another objective is to develop systems that exploit lymphocyte internalization to deliver photoactivatable drugs to malignant lymphoctyes. Finally, in two very speculative projects techniques will be developed to probe for the existence of RNA topoisomers and other techniques will be developed to produce fluorescently labeled proteins biosynthetically.