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Yuya Hayashi

Research

We are interested in imaging life at the interface with nanotechnology. Seeing is believing – but engineered materials at the nanoscale are too small to be seen with the naked eye, especially when they are hidden inside our body.  Starring zebrafish as a model organism to "see through" the tissues non-invasively, we explore how biological systems interact with nanoscale objects in real-time. We use a combination of genetic manipulation and microscopy approaches for in vivo imaging and screening at spatio-temporal resolutions unrivalled by existing mammalian models (see Figure and Movie).

Figure

Zebrafish embryos as an emerging research model for in vivo imaging and screening of nanomaterials. Transgenic lines with a cell type-specific fluorescent protein reporter allow us to study the dynamic behaviour of e.g. macrophages and how injected nanomaterials are cleared from the bloodstream in a living organism. Transmission electron microscopy approaches can then complement the real-time observations by visualising those processes at the nanoscale. (Image: Yuya Hayashi. Adapted from Hayashi et al. (2020) ACS Nano. Copyright 2020 American Chemical Society)

Featured article

"Differential Nanoparticle Sequestration by Macrophages and Scavenger Endothelial Cells Visualized in Vivo in Real-Time and at Ultrastructural Resolution" by Yuya Hayashi*, Masanari Takamiya, Pia Bomholt Jensen, Isaac Ojea-Jiménez, Hélicia Claude, Claude Antony, Kasper Kjær-Sørensen, Clemens Grabher, Thomas Boesen, Douglas Gilliland, Claus Oxvig, Uwe Strähle, and Carsten Weiss.

ACS Nano 14 (2020) pp. 1665-1681.

Current projects

Biological recognition of nanomaterials through a protein corona

What lies at the interface of biological receptors and nanoparticles? Over the past decade, nanoscientists have studied complex biophysical interactions that take place between biomolecules and nanoparticles. Today, it is widely accepted that cells recognise the biomolecules adsorbed to nanoparticles rather than the bare surface. Proteins are among those biomolecules that form a "corona" around the nanoparticle, and the corona profile is translated into a biological identity that can determine the nanoparticle's fate within a biological milieu.

Our interest is to unravel how innate immunity fights against those nanomaterials through recognition of their biological identities. The zebrafish embryo model now opens up a new opportunity to tackle this scientific question with the power of in vivo imaging at the high spatio-temporal resolution.

We work with the collaboration partner Prof. Duncan Sutherland at iNANO Interdisciplinary Nanoscience Center, Aarhus University.

TRAPping long-distance extracellular RNA communication in action

From an organ to another organ, cells send signals to coordinate the physiology of the entire body. A well-known example is signalling by hormones, but what if cells instead wish to deliver more complex messages than signals? A striking new discovery is the packaged delivery of small RNA via extracellular vesicles (EVs) that enables cell-cell communication over a long distance. The meaning of this biological process is, however, still poorly understood today. This is largely due to technical difficulties in the isolation of EVs (and small RNA therein) from complex biological fluids. The EVs encompass a wide range of vesicular entities, among which exosomes and microvesicles are two major EV types of particular interest in biomedical applications such as diagnostics and drug delivery. They are nanoscale vesicles nature has created, and thus the approaches we use for bionanoscience have technical overlaps with EV research.

Using zebrafish as an in vivo model, we aim to develop a revolutionary method bypassing the technical difficulties by directly capturing the small RNA "in transit" from donor cells to recipient cells. Combined with genetic manipulation, we use omics approaches for global profiling of the small RNA "in transit" and mRNA "in translation" to identify the potential targets of the small non-coding messages sent out by the donor cells.

Our collaboration partner for this project is Prof. Jørgen Kjems at iNANO Interdisciplinary Nanoscience Center, Aarhus University.

Want to inject something in zebrafish embryos?

Please contact Yuya Hayashi (yuya.hayashi@mbg.au.dk) to discuss about possibilities.