On the involvement of tRNAs and mRNA translation in peripheral neuropathy

“In this work, I worked with the common fruit fly to get a better understanding of a disease affected the peripheral nerves, the ones that allow you to move and the ones you use to sense. This disease is called Charcot-Marie-Tooth (CMT) peripheral neuropathy and many people suffer from it. Many different, genetic causes have been found for the disease, but no cure is available. Interestingly, over the last years, scientists have found that eight different members of a certain protein family are all affected in different patients with CMT. These proteins are essential in mRNA translation, the process in which your cells make new proteins. To get a better understanding of how this causes the disease, I have contributed to the development of a new technique to measure the rates of protein production. I helped to make it work in fruit flies too, so we could use it in our experiments. I further studied two of the eight affected proteins. I studied them in the fruit flies and observed how the flies also got problems walking. I then confirmed a previous finding from our lab that showed that not the protein itself, but its interaction partner, tRNA, is what is problematic. What happens is that the affected protein does not want to let go of its tRNA anymore, which means over time too little tRNA is available for the cell to continue producing proteins. We wanted to see if there were other aspects also contributing to the disease, but, based on our results, it seems unlikely. I then focused on the other partner, the tRNA, and tried to reduce only the level of tRNA in the fruit flies in a technological first. However, I did not get it to work properly in the time I had. Lastly, I also mutated flies to find new causes of the destruction of nerves and have an interesting list of candidates for follow-up research.”