Russell Foster: What is the body clock?

Every organism on Earth lives by some kind of clock. Our bodies are calibrated to the day night cycle of the area that they live in, and processes like hormone release and brain function are attuned to this periodic cycle too. But up until recently, we didn’t really know what drove this process. That was until work by Russell Foster and his team discovered which specific cells set the rhythm for the rest of our body. But before that, I began by asking him exactly what a body clock is, and how our understanding of it has evolved over time…

Russell - In the early days, we really thought there was 'the body clock', and there's a structure within the base of the brain called the suprachiasmatic nuclei. And that structure was shown way back, actually in the late 20s, to be really important in generating 24 hour patterns of rest and activity. But it wasn't clear how it worked. And certainly in the old days we thought that it was a sort of a cell cell interaction, that cells would interact in a form of a network to generate an oscillation. And what we thought is that this master clock imposed rhythmicity, so changes in our blood pressure, in our hormonal rhythms and all the rest of it, over the 24 hour day. And then it became clear that every cell in the body can probably generate a circadian oscillation. And I remember being at the meeting at the time when this emerged, and it was sort of an audible gasp because it changed the way we thought about the clock. And in fact, it's now very much considered to be a circadian network with billions and billions of individual cellular oscillators, all coordinating with each other, and with respect to that master clock in the brain, to produce an essential biology. And if you think about it, what do we need to do? We need to deliver the right stuff at the right concentrations to the right tissues and organs at the right time of the day. And that's what the circadian system, the body clock if you like, actually does it. Fine tunes our entire biology to the varied and complex demands of sitting on a planet that revolves once every 24 hours producing light, dark cycles, temperature cycles, and different availability of stuff.

Chris - That suprachiasmatic nucleus, the structure in the brain in the hypothalamus that does this, there's a sort of genetic clock ticking in there with one gene turns on, turns on the next one, turns off the first one. And it ticks around. So when that genetic ticking is taking place, how does that translate actually into a clock signal? How do those nerve cells change in response to that? And how do they transmit that time, if you like, to all those other cells in the body and all those other oscillators as you put them, all the other cells in our body that are keeping time in sync.

Russell - So what you've got is this fundamental molecular feedback loop with regulatory elements in the clock genes, but you also have those regulatory elements in a whole host of other sorts of genes. And so in the same way that they can feed back on themselves, they can also feed onto other genes and regulate their output. And so they may be genes which are involved in the generation of electrical responses or genes involved in the release of hormones. So this fundamental molecular oscillation could be translated into lots of different delivery mechanisms. And that's all turning out to be, again, amazingly exciting and interesting.

Chris - How far back in life's evolution do I have to go to find where these clocks started? Because you mentioned a planet that rotates in roughly 24 hours. Well, the world has always spun, so therefore, as for as long as we've had life, presumably we've needed to know the time

Russell - Well, exactly. And in fact, it's thought that the evolution of some sort of clock is a very, very ancient part of biology. It's been called a signature of life. And in fact, when individuals were looking for life on Mars, they were looking for the rhythmic production of organic molecules, for example. You know, because it's such a ubiquitous aspect of biology. I'm also really fascinated with evolution. And I find it extraordinary that the fundamental building blocks, the genes and their proteins that you find in us, are conserved in all vertebrates and invertebrates. So the same building blocks are present more or less in the entire animal lineage. Now what's fascinating is that the way we, the animal lineage, build its clocks is different from the green plants or indeed fungi. They have different genes and different proteins, but they also fundamentally use a molecular feedback loop. So it's a signature of life and it's very, very ancient.