Drug Delivery at the Immunological Synapse

我们已经给几乎所有不同的蛋白质分子起了名字，这些蛋白质分子调节着人类细胞之间的通讯。现在，当代细胞生物学的大胆目标是了解普通细胞中的10亿种蛋白质如何允许它们移动、繁殖、创造大脑或保护我们免受病毒和细菌的伤害。在这一前沿领域，成像技术在蛋白质相互作用的地点和时间发挥着重要作用。最近对几种蛋白质的成像已经在免疫细胞如何相互沟通以及如何识别疾病征兆方面产生了重要的新概念。免疫细胞与其他细胞接触的图像显示了临时的膜结构，通常被称为免疫突触，类似于神经细胞为了交流而相互制造的突触。据推测，这种免疫突触的一个功能是组装一个‘垫圈’，在某种程度上将突触裂隙与整体细胞外环境隔离开来。然而，突触作为衬垫的确切程度还没有被研究。这一基础知识对新药的设计具有重要意义，因为从长远来看，了解免疫突触在多大程度上以及如何被大量细胞外环境屏蔽，可以促进合理设计穿透免疫突触的药物，以更有效地发挥作用，例如阻止跨突触分泌的蛋白质。值得注意的是，为了实现拟议的实验，我们将开发新的成像技术，这些技术将在几个生物学研究领域引起广泛的兴趣。可在开发特定应用时申请专利。除了这里要研究的具体假设外，高分辨率显微镜在研究免疫细胞相互作用方面的应用在某种程度上也是探索性的和形成假设的；这仍然是一个非常年轻的领域，肯定会有更多的惊喜。

We have given names to nearly all the different protein molecules that mediate communication between human cells. Now, the audacious goal of contemporary cell biology is to understand how the billion proteins in an average cell allow them to move, multiply, create a brain or defend us against viruses and bacteria. Imaging where and when proteins interact with each other has a major role to play at this frontier. Recent imaging of just a few types of proteins has already led to important new concepts in how immune cells communicate with each other and how they recognize signs of disease. Images of immune cells contacting other cells have revealed temporary membrane structures, often called immune synapses, similar to the synapses that nerve cells make with one another for communication. It has been postulated that one function for such an immune synapse is to assemble a 'gasket' that to some extent isolates the synaptic cleft from the bulk extracellular environment. However, the precise extent as to which the synapse acts as a gasket has not been studied. This fundamental knowledge can have a major importance for the design of novel drugs, because understanding to what extent and how the immune synapse is shielded from the bulk extracellular environment could, in the longer term, facilitate the rational design of drugs that penetrate the immune synapse to work more effectively, e.g. for blocking proteins secreted across the synapse. It may also be useful to note that to realize the proposed experiments we will exploit new imaging technologies which will be of broad interest across several biological research fields. Patents may be sought upon development of specific applications. In addition to the specific hypotheses to be studied here, the application of high-resolution microscopy to study immune cell interactions is also to some extent explorative and hypothesis-forming; this is still a very young field and more surprises are surely in store.