Finding the first heartbeat Dr Richard Tyser is the Charles Darwin Award Lecture winner for Agriculture, Biological and Medical Sciences. This Award is in recognition of his cutting-edge work and committed public engagement efforts. Full details of the 2020 Award Lecture winners can be found here: www.britishscienceassociation.org/news/introducing-our-2020-award-lecturers The following interview with Richard has been written by Alan Barker, freelance writer ----------------- Richard Tyser is investigating how embryonic heartbeats begin. What he’s found is extraordinary, and could have enormous implications for the treatment of heart disease. It’s a rather awesome question: when does the heart first start to beat? Well, the embryonic heart is the first organ to form and start functioning. It’s essential in supplying the developing embryo with oxygen and nutrients. How does it start to beat? You’d think that you’d need a fully formed heart before you could have a heartbeat. But it turns out that’s not the case. We’ve found that heartbeats actually begin much earlier, before the heart – as we know it in the adult – has formed. We’ve been looking at the cardiac crescent, a flat sheet of progenitor heart cells – cells that will eventually develop into the adult heart. And we can see these cells beating. So, we have a heartbeat before we have a heart… Well: an embryo has a heartbeat before it has a fully formed heart – in fact, heart cells start beating even before the formation of a brain. I hadn’t really thought about the deeper questions relating to this until a science communication event, when I was asked: “Is that when life starts?” It was a difficult question to answer, but I don’t quite see it as the start of life, given that the embryo has already begun to form but there isn’t a brain yet. What’s causing the beating? At its most basic, heartbeats are coordinated bursts of calcium ions increasing and decreasing in a heart cell. When the calcium ions increase, they can cause the cell to contract and when they decrease the cell relaxes. In the adult heart, you have synchronised waves of calcium across the whole heart; that’s your heartbeat. In the cardiac crescent, the progenitor cells have random bursts of calcium ions, then, at one particular moment, in one small region, they become synchronised; this synchronised region gets bigger and then the cells start to beat. And when is this happening? In mouse embryos, which take 21 days to develop, the heartbeat starts at about day eight. In a human, the equivalent developmental stage is about 19 to 21 days. How do you know that? The number’s based on something called morphological staging; we haven’t yet conducted experiments on human embryos at this early stage of development. What synchronises the beating? That’s the question I’m trying to address with my current British Heart Foundation fellowship. Cells could be coupling and then communicating with each other directly. Maybe one type of cell gives signals to the other types. Maybe, when cells develop to a certain point, they express a certain protein which makes them synchronise. How many different types of cell are involved? That’s a good question, and one we’re trying to work out. I’ve been using a technique called single cell RNA sequencing to look at all the genes expressed in a single cell, and that identifies the cell type. Then we can begin to see whether there might be a specific cell type with a pacemaker function, or perhaps find the genes that are responsible for coupling cells together. We’re also doing live imaging to see where and when this synchronisation occurs. So, with these two techniques, we can build up a really good map of the cell types and where they are as the cardiac crescent develops. What’s the sequence of events in this process? We’ve found that a particular protein – it’s called NCX1 – seems to be necessary to trigger the calcium bursts that set up the heartbeat. But it also influences how calcium signals activate other proteins to turn genes on and off, and create the cells that you need to build a heart. There is a link between form and function. We’re trying to tease out these two parts – the physiology part and the signalling part. So, the process of generating the heartbeat is also involved in how the heart itself develops. And not just the heart. If you stop the heart beating – by inhibiting this protein NCX1 – the blood doesn’t develop properly; in fact, the whole embryo will be affected and fail to form. What’s the wider significance of this work? I’d say that there are three main problems that our work could help tackle. But, as with all science, addressing fundamental research questions can also have unexpectedly significant impacts. First, understanding embryonic heart development will help us to understand congenital heart defects. Secondly, it might help us treat heart disease. In the UK, 7 out of 10 people now survive a heart attack. But that means more people have heart failure: they’re living with damaged hearts. During heart failure, mechanisms present during heart development are reactivated, which in the adult heart are detrimental. If we can understand these mechanisms in both embryonic and adult hearts, we can hopefully come up with treatments. And then, thirdly, there’s huge potential in regenerative medicine. By understanding heart development, we’re writing a kind of Lego manual for how to build a heart – which we hope can be used to build new heart tissue. Alan Barker is a writer, trainer and coach specialising in communication skills. He has been working with the British Science Association since 2015. Alan’s webinar, Storytelling for Scientists, is on the 3M YouTube channel.