Esther Nolte-'t Hoen

I’m eager to explore how these tiny vesicles steer the function of immune cells

"I'm fascinated by the immune system. How do immune cells use RNA-encrypted messages to communicate with other cells? These messages are packaged in a special communication unit called ‘extracellular vesicles’. I’m eager to explore how these tiny vesicles steer the function of immune cells.

Active in all body parts
The key word for a well-functioning immune system is ‘communication’. I’ve been active in the field of immune cell communication since the start of my PhD. What fascinates me in the immune system is that it is active in almost all parts of our body. It needs to deal with a large number of challenges imposed on the body, such as the presence of harmless microbiota, pathogenic microbes, cancer cells, and food components. Various cell types present in the immune system need to communicate and collaborate to raise and control immune responses and protect the body.

Tiny particles
My research focuses on extracellular vesicles (EVs), a very special communication unit that cells use to influence each other’s behaviour. These tiny (50-150 nm) particles are entities enclosed by a lipid bilayer that contain a variety of proteins and genetic components. Only the past 10 to 15 years, it has become clear that the release of EV is a conserved means of cellular communication, that these vesicles are present in virtually all body fluids, and that cells can tightly regulate the molecular composition of these vesicles. These aspects make vesicles an interesting topic for both fundamental research and diagnostic purposes.

Young research field
It is both exciting and good fun to work in this young research field, because there is still so much to discover. Utrecht has been involved in this research area since its very early days and we have built up extensive experience with vesicle isolation and characterisation techniques. Within our research group, we have developed a unique flow cytometry-based technique for high-throughput characterisation of individual EVs. Furthermore, I was one of the first to publish an in-depth characterisation of the RNA content of extracellular vesicles.

Immune cell communication
With regard to size, composition and biogenesis, EV show similarities with viruses. I was therefore convinced that we as EV biologists could learn from viruses with regard to biogenesis of EVs and functional delivery of molecular components to target cells. This idea formed the basis of the ‘INTERCOM’ ERC starting grant application, which was granted in 2013. The goal of INTERCOM is to understand how the RNA content of vesicles released by immune cells contributes to immune cell communication and regulation of ensuing immune responses. We have found that immune cells instructed to activate or suppress immune responses release different RNA-encrypted messages packaged in vesicles.

Integrating knowledge
Our current research focuses on how viruses interfere in the release and molecular contents of the vesicles. This can help to understand the role of extracellular vesicles in virus propagation and the immune response against viruses. The INTERCOM project is highly interdisciplinary and aims to integrate knowledge from the fields of cell biology, immunology, genomics, and virology. Although challenging, I am sure that by overspanning different research disciplines we can increase our conceptual knowledge of biological systems."