 When we think about the genetic material, the DNA of a chromosome, all cells have to make a fundamental decision as to whether transcribe that DNA into RNA, which will then allow the function of the cell, production of proteins and so on, or to replicate it into more DNA. And these two are competing functions between the RNA polymerase and the DNA polymerase responsible for replication. We work on something called RNA interference, which we showed about 15 years ago now, can silence genes by removing RNA polymerase 2 and by stimulating the production of something called heterochromatin, the most condensed part of the chromosome, which doesn't allow transcription. And it promotes, RNAi promotes the formation of heterochromatin, which has important functions in chromosome segregation. We work with a model organism called fission yeast, they're very simple. And they have RNA interference. But when we make mutants in these fission yeast that no longer have the RNA interference, they can no longer silence genes using, by removing RNA polymerase 2. But what we found is that they can no longer survive without DNA replication in a quiescent state. Now, most cells in animals and plants are non-dividing. That doesn't mean they're not alive. They can be stimulated, quiescent cells can be stimulated to re-enter the cell cycle. And because this involves both the reprogramming from division to quiescence and the stable maintenance of quiescence for very long periods, but in a reversible way, we can think of this as an epigenetic transition. So they're not changing their genetic constitution while doing this, but they must be doing something that's both reversible on the one hand and very stable on the other in order to be able to maintain and enter this quiescent state. And so RNA interference is one of the most important epigenetic mechanisms. It guides many of the other epigenetic mechanisms. And so perhaps it should come as no surprise that you need RNA interference to enter and maintain quiescence. We found through genetic analysis that the reason for this was that RNA interference seems to interact genetically with transcription itself, with the RNA polymerase. Both RNA polymerase one, which is responsible for rDNA, ribosomal DNA transcription, as well as RNA polymerase two, which transcribes the rest of the genome. And by releasing these at different points in the cell cycle, either in dividing cells or quiescence, RNAi controls the formation of these silent, compact heterochromatic domains. If those domains are unmanaged, if they get out of control, they will kill the cell. And that's what's happening in quiescent cells that don't have RNAi. One of the things that this explains very neatly is that organisms that have lost RNAi naturally in nature, and there are a few of these, have also lost heterochromatin. They have to, because otherwise the toxic heterochromant will kill them during quiescence. So this is a very, very powerful explanation for this interesting evolutionary trend. Importantly, it might also explain the key role that RNAi plays in stem cells, which are quiescent for much of their life, and also in cancer, which, after all, is the stimulation of cells that are normally quiescent, normal benign cells of the body to divide and proliferate. And that transition is often accompanied by mutations in RNAi, just like our mutations in fish and yeast.