Sir Michael Berridge
Biochemist whose research on blowfly salivary glands unlocked the secrets of cell behaviour
SIR MICHAEL BERRIDGE, who has died aged 81, was a physiologist and biochemist whose discovery of the mechanism whereby cells convert external stimuli into the internal signals that govern their behaviour led to a paradigm shift in scientific understanding of cell regulation and shed light on the biology of disease from cancer to cardiovascular and neurological diseases.
Scientists discovered long ago that proteins, such as growth factors or hormones, act as messengers in the body, but most of them stop short at the membrane that surrounds the cell. Inside the cell, calcium ions seemed to be responsible for triggering cell behaviour, but the mystery was how signals from outside were carried into the cell to mobilise calcium.
Berridge’s studies on cell signalling began with research on the salivary gland of the blowfly, where he established that cyclic adenosine monophosphate (cyclic AMP) and calcium worked together as intracellular “second messengers” to control fluid secretion. Others had shown how receptors within the cell membrane translate external stimuli into production of cyclic AMP, but the links to calcium signals were not known.
Berridge devised methods that exploited the ability of insect salivary glands to secrete copious amounts of saliva which they must do if the fly is to feed before being swatted. This preparation allowed him to show that external stimuli caused the formation of an intracellular molecule called inositol trisphosphate (IP3) by degrading a component of the membrane around the cell. He described his discovery as “a eureka moment” and the paper, published in Nature in 1983, in which he set out for the first time the role of IP3 as a calciummobilising messenger, became one of the most cited in the field.
While his early work on fly spittle had been considered arcane by many, it paved the way for the discovery of the links between extracellular stimuli and calcium signals.
It quickly became clear that IP3 was a ubiquitous intracellular messenger, and that its ability to release calcium from intracellular stores regulated processes as diverse as fertilisation, development of the early embryo, muscle contraction, communication between nerve cells, blood clotting and much more, including cell death.
Berridge’s influential reviews and beautifully crafted talks brought the significance of IP3 signalling to a wide audience, and recognition that it also provided insight into diseases as diverse as cancer, bipolar disorder, cardiovascular disease and Alzheimer’s disease.
Michael John Berridge was born on October 22 1938 in Southern Rhodesia (now Zimbabwe). Inspired by a childhood love of nature and an enthusiastic biology teacher, he read Zoology and Chemistry at the University of Rhodesia and Nyasaland.
After graduating with a First, he won a Commonwealth Scholarship to do a PHD on nitrogen excretion in the African cotton stainer (a red bug) at the University of Cambridge under the entomologist Sir Vincent Wigglesworth.
He became interested in how hormones stimulate insect cells to secrete saliva and went on to do postdoctoral research on cell signalling at the University of Virginia in Charlottesville, and then at Case Western Reserve University in Cleveland.
Returning to Cambridge in 1969, he became senior, and later principal, scientific officer of the Agricultural and Food Research Council Unit of Invertebrate Chemistry and Physiology at the university’s Department of Zoology. He served as senior principal scientific officer of the Unit of Insect Neurophysiology and Pharmacology from 1978 until 1990. He was also appointed a fellow of Trinity College in 1972 and inspired generations of Trinity scientists in his stimulating cell biology supervisions.
He then joined the Laboratory of Molecular Signalling of the Babraham Institute, the life sciences research institution situated six miles outside Cambridge, as deputy chief scientist. He became head of the laboratory in 1994, when he was also appointed honorary professor of cell signalling at the university. On his retirement in 2004 he was appointed the first Emeritus Babraham Fellow.
Berridge’s breakthrough discovery led to a lifelong interest in the role of calcium in normal and diseased cells and tissues, and he inspired and supported many PHD students, enthusing them with the story of his own research career and endowing an annual prize which recognises research excellence by PHD or postdoctoral scientists.
The importance of his work was recognised with the award of many international prizes. He was elected a Fellow of the Royal Society in 1984, and to the National Academy of Sciences and the American Academy of Arts and Sciences in 1999. He was a founding member of the Academy of Medical Sciences, and in 1998 was knighted by the Queen for “service to science”.
Michael Berridge married, in 1965, Susan, née Graham Winter. She survives him with their son and daughter.
Sir Michael Berridge, born October 22 1938, died February 13 2020