Genetic competence apparatus of Bacillus subtilis

这项拟议研究的长期目标是确定通过核孔复合体的双向运输机制。进出核团的运输始于一套专门的运输受体对运输的货物的识别。停靠在核孔后，货物-受体复合体通过排列着核孔素的孔道移动。货物的装卸以及运输的复合体与核孔的相互作用是核运输的决定性事件。在许多情况下，RanGTPase及其调节因子控制着毛孔的运动方向。将核糖体等大型复合体作为核外出口的目标，使核运输过程变得更加复杂。其具体目的是确定：1)核糖体如何输出到核外；2)核运输因子与核孔复合体接触；3)核内RAN调控因子的组织整合了核运输和基因调控；以及4)核膜的完整性被维持。核定位的缺陷与许多疾病有关，从而导致该项目与健康有关。核质运输为基因调控提供了一种模式，以响应生长信号、应激、病毒感染、免疫反应和肿瘤抑制因子的活性。某些蛋白质的活性可以通过改变它们在细胞质和核之间的细胞内位置而受到影响，从而使核运输成为潜在的治疗靶点。总而言之，了解核运输的过程以及它是如何被调控的，可能会导致新的药物靶点和加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.