The supramolecular dynamics of human immune cell recognition and communication

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。探索这种蛋白质变化的排列是如何发生的，以及它们是如何控制免疫细胞通信的，这是免疫突触概念开启的一门新科学。我的研究团队和其他人最近也观察到，由细胞膜组成的长管很容易在免疫细胞之间形成。我们称这些连接为膜纳米管，它们可以构成一种新的机制，用于相隔很远的细胞之间的通信。然而，代价是艾滋病毒等病毒可能利用这些连接在细胞之间有效传播。因此，我们的目标是确定这些连接是如何形成的，以及它们对人类免疫系统有什么功能后果。我们还观察到，RNA可以在细胞之间进行交流，这表明了一种新的、意想不到的细胞相互作用机制。这对于理解和治疗一系列疾病可能非常重要，我们在这里的目的是确定这种现象的机制和功能。研究这些新现象可以为细胞-细胞相互作用如何导致对肿瘤和病毒感染细胞的有效免疫监测奠定重要的新研究领域。在我的实验室研究的许多具体例子都具有明显的医学重要性。例如，研究巨噬细胞和自然杀伤细胞之间的相互作用可能被证明与理解脓毒症的根本原因有关。此外，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研究领域引起广泛兴趣，并可能在开发特定应用时申请专利。令人兴奋的是，免疫细胞相互作用的高分辨率显微镜仍然是一个非常年轻的领域，肯定会有更多令人惊讶的事情。

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. Exploring how such changing arrangements of proteins occur and how they control immune cell communication is the new science opened up by the immune synapse concept. My research team and others have also very recently observed that long tubes, made of cell membrane, readily form between immune cells. We called these connections membrane nanotubes and they could constitute a new mechanism for communication between cells that are far apart. A cost, however, is that viruses such as HIV may use these connections to efficiently spread between cells. Thus, we aim to determine how these connections form and what functional consequences they have for the human immune system. We have also observed that RNA can traffic between cells suggesting a new and unexpected mechanism by which cells interact with each other. This could be very important in understanding and treating a range of diseases and we aim here to determine mechanisms and functions for this phenomenon. Studying these new phenomena can seed important new research areas for how cell-cell interactions lead to effective immune surveillance of tumours and viral-infected cells. Many of the specific examples studied in my laboratory have clear medical importance. For example, studying interactions between macrophages and Natural Killer cells is likely to prove relevant in understanding the underlying causes of sepsis. Also, to realize the proposed experiments we will exploit new imaging technologies, which will be of broad interest across several biological research fields and patents may be sought upon development of specific applications. Excitingly, high-resolution microscopy of immune cell interactions is still a very young field and more surprises are surely in store.