Eureka Moments: the Key That Unlocked Calcium

Centenary News

Michael Berridge in conversation with Robin Irvine Eureka moments: the key that unlocked calcium

Sheila Alink-Brunsdon (Head of Group – Society Activities) Downloaded from http://portlandpress.com/biochemist/article-pdf/33/1/40/4085/bio033010040.pdf by guest on 01 October 2021

As part of our Centenary celebrations, a number of the Society’s Honorary Members have been asked to talk about the important moments in their careers and the future of the discipline. These interviews will be made available throughout the year on the Society’s website as a series of podcasts.

come over to the UK to do his PhD at Cambridge un- der Sir Vincent Wigglesworth. Michael remembered: “It was remarkable to come and work with essentially the father of insect physiology. It was tremendously inspiring to work with someone like that.” It was when working on the salivary glands of flies that he soon realized he would need new tech- niques to progress further. The problem that inter- ested Michael was how a hormone made a cell secrete saliva. “We all need to respond to our environment and that process begins at a cellular level. A signal reaches the surface of a cell, but how does that makes

Sir Michael and Robin reminiscing

The first to be released is that of Professor Sir Michael Berridge who spoke to Professor Robin Irvine about his ‘eureka moment’ in calcium signalling and his passion for trying to find the solution to interesting problems. Michael Berridge and Robin Irvine are old friends and, coming from completely different fields of science, they changed our understanding of cell signalling. Robin Irvine’s introduction recalls the compatible nature of their back- grounds and his delight in being involved, “Mike was a cell physiologist who knew a huge amount about calcium, cAMP and so on, but didn’t know one end of an inositol ring from another. Whereas I was an inositol lipid biochemist who didn’t really know anything about cell biology. The complementarity in our skills was good for both of us, but for me to end up in something that was so important, that’s just one of those strokes of luck that everyone hopes happens to them – and it happened to me.” Michael Berridge starts by discussing his early life in Zimbabwe (formerly Rhodesia), the effect that this magical place had on him, his love of wildlife and the important influence of his biology teacher Pamela Bates. He would eventually Preparing to film in Robin’s office

it change its behaviour?” Michael knew that calcium was involved, but that was not the whole story. Calcium has a number of unique properties that enable it to bind to proteins so they can change their confirmation and that is how signalling works. IP3 (inisotol trisphosphate) comes from the inositol lipids found on the cell membrane. Michael thought

IP3 might be that crucial chemical messenger that connects the hormone outside the cell to the calcium stores inside. It was Bob Michell in Birmingham about 8 years

before who had suggested that there is a link between Downloaded from http://portlandpress.com/biochemist/article-pdf/33/1/40/4085/bio033010040.pdf by guest on 01 October 2021 insitol lipids and calcium. Although that link was not clear, something happened when you stimulated cells to their insitol lipids and then the calcium increased, and it was really set for Michael to realize that it was

IP3, which was being produced from these phospholipids by the breakdown of these phospholipids that could be this second messenger. Michael remembers the moment distinctly when Filming the interview it was proved that IP3 was the messenger, “When I did the experiments and I suddenly saw the one Like many scientific discoveries, Robin Irvine second reading and the IP3 was up and I remember highlights the apparent simplicity of the idea after its being so excited and it was a real eureka moment – discovery, “So IP3 was being produced in the right that this must be the way it works, that this is the place at the right time and now the question is can second messenger.” we now establish that IP3 is actually doing that. You “When I did the experiments and I suddenly saw the one second reading and the IP3 was up and I remember being so excited and it was a real eureka moment – that this must be the way it works, that this is the second messenger.”

can look back at say ‘well, it is obvious isn’t it’; with the benefit of hindsight, it’s obvious, but the thing about breakthroughs is that they’re only obvious after they’ve happened.” Looking to the future, Michael spoke about the excitement that he still feels about research and the impact of imaging “What excites me is unsolved problems and to see if I have the tools to at least understand it, to try understand what this phenomenon is […] The development of imaging has completely transformed the calcium signalling field. We knew quite a lot, but, compared with what we know now about the precision of the calcium signal both spa- tially and temporally, calcium is the key to the signalling mechanism.” ■

The Eureka Moments podcasts will be available on the Biochemical Society website at www.biochemistry.org/ Members of Robin’s laboratory enjoying watching the filming Centenary/EurekaMoments