GENE STRUCTURE, ARRANGEMENT, DYNAMICS, AND EXPRESSION

该计划的目标是开发新的物理和化学 技术来解决以前棘手的问题，在细胞和分子 生物学 一半以上的精力将用于改进 脉冲场梯度凝胶电泳及其高效液相色谱技术的发展 切割DNA分子的特殊方法。 结合这些技术 将允许快速绘制人类基因图谱，并对各种基因进行分子分析。 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肿瘤细胞核染色质的拓扑性质 整个哺乳动物染色体 目的是了解染色质 基因表达过程中的结构和能量变化以及 DNA的刚性用于正常和异常的基因调节。 另一 该计划的一部分涉及大分子的内化， 淋巴细胞 一个目标是研究特定的淋巴细胞如何能够 以内化特定的组织相容性抗原。 另一个目的 是开发一种利用淋巴细胞内化的系统， 光活化药物治疗恶性淋巴瘤。 最后，在两个非常 投机项目技术将被开发，以探索 RNA拓扑异构体和其他技术的存在将被开发， 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.