Project description
Transparent tissues: the benefits are clear to see
You cannot see into most tissues with an optical microscope, but there are some exceptions. A combination of high-tech genetics methodologies and simple optical microscopes has pushed our understanding of health and disease mechanisms thanks to the tiny zebrafish. There are many reasons why this minnow has been such a fruitful model system, its transparency being one of them. The EU-funded GHOSTS project plans to harness directed evolution to create many more examples of transparency, enhancing the ability of scientists to study model cells and tissues using simple optical microscopes for unprecedented insight. The technique could have a significant impact on fields ranging from basic discovery and drug development to therapeutics.
Objective
Most biological tissues are optically opaque, largely precluding access by light microscopy. In stark contrast, some living tissues and organisms are highly transparent. Examples include many deep-sea fish, your retina, and cells that we exposed to directed evolution.
Here we propose to uncover the genetic basis of tissue transparency, such that living cells and tissue cultures can be optically cleared by precision genetics. For this we will combine insights into origins of retina transparency, and a set of unique methods, to answer the question how genetically cells become more transparent during directed evolution.
Specifically, we will use a three-fold approach to find transparency genes that do not compromise cellular integrity. For this we will use i) directed evolution towards transparency while co-selecting for cell fitness, ii) extensive phenotyping of transparent cells, both optically and functionally, and iii) use of transcriptomics to rule out stressed cells, and those that deviate too much from wildtype gene expression profiles.
Knowing about physiological transparency genes will allow unprecedented insights into living tissues. If model tissues in the lab were just 1% as transparent as some glass-like fish found in the deep sea, optical microscopes could unleash their full potential, and enable high resolution views into developmental processes in their native environment. We see further transformative potential especially in the fields of organotypic tissue models, functional brain imaging, as well as pharmaceutical screens in 3D tissue cultures.
Fields of science
Programme(s)
Topic(s)
Funding Scheme
ERC-STG - Starting GrantHost institution
76131 Karlsruhe
Germany