Genetic competence apparatus of Bacillus subtilis

拟议的研究的长期目标是确定跨核孔复合体的双向运输机制。转运进出细胞核始于一组专门的转运受体对转运的货物的识别。在对接在核孔后，货物-受体复合物移动通过孔通道，其内衬有核孔蛋白。货物的装载和卸载以及被运输的复合物与核孔的相互作用是核运输的定义事件。在许多情况下，RanGT及其调节剂控制通过孔的运动方向。靶向大的复合物，如核糖体，以输出到细胞核外，对核运输过程施加了更大的复杂性。具体目标是确定如何：1）核糖体输出到细胞核外; 2）核转运因子与核孔复合体接触; 3）细胞核中Ran调节因子的组织整合了核转运和基因调节;和4）维持核被膜的完整性。核定位缺陷与许多疾病有关，因此有助于该项目的健康相关性。细胞核-细胞质转运提供了响应于例如生长信号、应激、病毒感染、免疫应答和肿瘤抑制因子活性的基因控制的调节模式。某些蛋白质的活性可以通过改变它们在细胞质和细胞核之间的细胞内位置而受到影响，从而使核转运成为潜在的治疗靶点。总而言之，了解核转运的过程及其如何调节，可能会导致新的药物靶点和增强基于病毒的基因疗法的方法。

The long-term objective of the proposed research is to determine the mechanisms of bidirectional transport across the nuclear pore complex. Transport in and out of the nucleus begins with recognition of the transported cargo by a dedicated set of transport receptors. After docking at the nuclear pore, the cargo-receptor complex moves through the pore channel, which is lined with nucleoporins. Loading and unloading of cargoes and interactions of the transported complexes with the nuclear pore are the defining events of nuclear transport. In many cases, the RanGTPase and its regulators controt the direction of movement through the pore. Targeting of large complexes such as the ribosome for export out of the nucleus imposes an even greater complexity on the process of nuclear transport. The Specific Aims are to determine how: 1) ribosomes are exported out of the nucleus; 2) nuclear transport factors make contact with the nuclear pore complex; 3) the organization of the Ran regulators in the nucleus integrates nuclear transport and gene regulation; and 4) the integrity of the nuclear envelope is maintained. Defects in nuclear localization are associated with a number of diseases thus contributing to the health-relatedness of the project. Nuclear-cytoplasmic transport provides a mode of regulation for gene control in response to, for example, growth cues, stress, viral infection, immune response, and activity of tumor suppressors. The activity of certain proteins can be affected by altering their intraceltular location between the cytoplasm and the nucleus making nuclear transport a potential therapeutic target. In sum, understanding the process of nuclear transport and how it is regulated, may lead to new drug targets and ways to enhance viral-based gene therapies.