Immune cells reach across gaps to touch one another with thin membrane tubes, and they can even swap RNA through these connections. Researchers have only recently spotted these behaviours, and no one yet knows how they work or what they control. The problem is that standard models of immune communication assume cells must either touch directly or release chemical signals into the fluid around them. These newly seen membrane nanotubes and RNA transfers suggest a third, faster route—one that could explain how immune cells coordinate attacks on tumours or infected cells, but also how HIV might spread more efficiently from cell to cell. This project will use high-resolution microscopy to watch the tubes form and track what moves through them. If it succeeds, it will open a new chapter in how we understand cell-to-cell signalling, with direct relevance to sepsis, viral infection, and cancer surveillance. The work is fundamental science: no immediate clinical tool will emerge, but the imaging techniques developed here could be patented and applied across many areas of biology.
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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.
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