Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - UAAWORM (Establishing genetic code expansion as a tool to study neuronal circuit function in an animal)

Teaser

The aim of our research is to take an established multicellular model organism with an artificially re-programmed genetic code and develop it into a system to tackle fundamental biological questions. We will initially focus on the nervous system of the nematode worm C...

Summary

The aim of our research is to take an established multicellular model organism with an artificially re-programmed genetic code and develop it into a system to tackle fundamental biological questions. We will initially focus on the nervous system of the nematode worm C. elegans.

We have previously introduced genetic code expansion to C. elegans. It allows the site-specific introduction of chemically synthesized non-canonical amino acids (ncAA) into proteins of interest.

In the past years the field of genetic code expansion has seen significant progress, allowing the incorporation of a growing range of ncAA in diverse systems. While the use of ncAA is still in its infancy, it is beginning to significantly impact the study of previously intractable biological problems. ncAA have been used to site specifically install post-translational modifications, introduce chemical handles that allow the site specific labeling of proteins, and create photo-activateable versions of proteins in vivo using photo-caged amino acids.
Many biological phenomena such as development, ageing or the functioning of nervous systems can only be studied in a multicellular context. We are currently one of very few labs world-wide, capable of using ncAA outside single celled systems. We are developing a new type of toolset to study biological processes inside whole multicellular organisms with a level of precision that goes far beyond the current state of the art. Once established, we aim to apply our tools to study neurobiological questions, focusing on the contribution of single cells and individual connections to the functioning of neural circuits.

The tools we are developing are likely to have significant impact in the life sciences. While we are initially developing these tools in and for C. elegans, they will be transferrable to other systems, since the genetic components we use are functional in all eukaryotic model organisms.

Work performed

We have introduced a number of non-canonical amino acids to C. elegans and have used them to develop new tools to study the worm\'s nervous system.

Final results

The tools we have developed are beyond the state of the art and until the end of the project we hope to use them to perform analysis of neural circuits on C. elegans at a level not possible using tools available thus far.