The discovery of calcium-mediated signalling pathways in the regulation of cellular function has truly revolutionized the fields of life science and medicine. The knowledge gained on how various factors increase calcium mobilization and how calcium controls cellular activity has widely expanded the areas of cell and molecular biology, and has led to the development of novel therapeutic strategies ranging from the treatment of heart disease to the improvement of learning and memory. These discoveries represent one of the most important cell signalling pathways in biology and have changed forever the way we think about prevention and treatment of disease.

Cellular communication occurs through chemical signals such as hormones, neurotransmitters and nitric oxide, which act via specific receptors or receptive molecules and are linked to diverse intracellular and extracellular signalling pathways. Berridge’s major achievement was to discover one such pathway that is linked to the hydrolysis of inositol lipids. This signalling system liberates two key second messengers, namely, IP3 (inositol 1,4,5-trisphosphate) and DAG (diacylglycerol). IP3 was discovered by Berridge, who showed that it functioned to release calcium from internal stores. This IP3/Ca2+ signalling system is of fundamental importance in regulating diverse cellular processes such as muscle contraction, cell growth and differentiation, secretion, fertilization, synaptic plasticity and information processing.

In the early 1970s, Berridge published a series of papers demonstrating that calcium and cyclic AMP functioned as separate and distinct signalling pathways that interacted with each other. Then, he published a series of papers leading to his discovery that IP3 was the messenger linking surface receptors to the mobilization of internal calcium (Biochem. J. 212: 849-858, 1983). Berridge’s discovery that IP3 functioned as a messenger molecule started an avalanche of work on the metabolism of inositol phosphates and on the calcium mobilizing action of IP3.

Berridge’s work on the spatial and temporal aspects of calcium signalling has laid the foundation for our current understanding of how information is encoded and decoded in the nervous system and in the cardiovascular system. His discoveries have impacted on widely diverse areas of biology and medicine such as memory and learning, cell growth, fertilization, myocardial contraction, glandular secretion and the mechanism of action of lithium.

The impact of these discoveries on the betterment of human kind has been astounding. The seminal contributions made by Berridge on IP3 and its role in calcium signalling made it possible to unravel numerous signalling pathways in biology and to show the links between such pathways and the central role played by calcium. The work of Berridge has had many practical consequences, not only in establishing a basis for our understanding of how cells are regulated but also in providing novel insights into a variety of human diseases.

Life Science and Medicine Selection Committee
The Shaw Prize

2 September 2005, Hong Kong