Well if that’s not one of the click baitiest titles you’ve ever seen. But that’s what I hope being part of with my PhD project.
In the last article I explained what Telomeres are and why they are important as one of the possible keys to aging on one and cancer on the other side. If you haven’t read the article yet, you can find it here.
When it comes to Telomeres it’s all about their length and its changes over time. If Telomeres degrade it is a sign of cellular stress (in some cases the opposite is true) or strong proliferation and if they reach a certain critical length they stop the cell from division and send it into senescence. If a cancer cell wants to divide further it has to overcome this brink and find a way to elongate its Telomeres.
This shows you why drugs that influence Telomere length (in either way) have a huge potential. But how do you find these drugs? There are several answers to this question however often the answer is high throughput screening. Which is a nice word for trial and error.
In high throughput screens you develope a system that gives you an easy, reproducible and cheap read-out for the effect you hope for and then you make tens or even hundreds of thousands of experiments in parallel with huge libraries of chemical compounds. If some of them show a promising effect you try to reproduce that effect first in the same and later in other experimental setups. Then you try to find out how your candidate compounds work, if they are toxic and other questions before you can start developing a drug from them.
For Telomere length there is currently already a problem in the first step. There is currently not yet a really easy, cheap, quick way to measure Telomere length in high throughput assays. For an overview on the currently available options you can read this review paper by Lai et al. 2011
My idea seems to be an easy (if probably not very accurate) option. Telomeres are normally quite tightly packed with proteins. I want to use this Telosome as a molecular ruler. My idea is to optically tag one or more of these proteins and look for a correlation between an optical read out from these tags and the length of the Telomeres. If I find this correlation I only have to calibrate it and I’m ready to screen for the pill against aging or cancer.
In the first step I’m using the bakers yeast Saccharomyces Cerevisiae as a model. I’ll explain a little more about the advantages and disadvantages of this system in another article. For now one of the advantages is that my lab has a library of yeast strains with tagged proteins. These tagged proteins are fusion proteins that were made by adding the genetic code code for Green Fluorescent Protein (GFP) to end of the code for (basically all) yeast proteins.
So in the first step I’m just taking yeast stains out of the – 80 °C freezer and revive them. Now I only have to check the fluorescence signal from cells with different Telomere lengths and see if there is a difference.
It could be so easy but there’s a problem with yeast. It doesn’t age or at least it keeps it’s Telomeres very constant in length using Telomerase. So I first have to teach my yeast to age like our somatic cells. I do this by disabling their Telomerase. I thought about three different methods of doing this that I’m currently working on but I’ll explain them in other articles.
On the other hand I can not only make their Telomeres shorter but also longer. This is interestingly done by cultivating the cells in 5 % alcohol.
If I don’t see a correlation in this easy system I have a few more elegant ideas that I’ll explain in other articles.