Affiliation:
1. Physiological Laboratory and Department of Biochemistry, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
Abstract
Roger Yonchien Tsien displayed precocious childhood talents in chemistry. After graduating from Harvard University in chemistry and physics in 1972, he pursued a PhD programme in the Physiological Laboratory, Cambridge, under the supervison of Professor Richard Adrian (FRS 1977) with Marshal Scholarship support. His thesis ‘The design and use of organic chemical tools in cellular physiology’ won the Gedge Prize and a Comyns Berkeley Research Fellowship by Gonville and Caius College, supporting his postdoctoral work developing Ca
2+
-sensitive electrodes and fluorescent probes measuring cellular [Ca
2+
]. His novel tetracarboxylate quin-2 readily accessed cells as its subsequently cleavable acetomethoxy ester and signalled in the physiological [Ca
2+
] range. At Berkeley, further improved ratiometric and strongly fluorescent probes included the Ca
2+
-sensing indo-1, fura-2 and fluo-3 sensors for other strategic ions and molecules that could photolytically uncage key intracellular regulators. At San Diego, design of fluorescent protein complexes built from the cAMP-binding phosphokinase A was followed by Nobel prizewinning work expressing green-fluorescent protein (GFP) and developing spectral GFP variants forming fluorescent resonance energy transfer (FRET) pairs. Their conjugation with further proteins specifically binding particular ions or molecules under study permitted measurement of these by optical methods. Further detector protein complexes such as DsRed, fluorescent at longer wavelengths, were to complement GFP. These interests culminated in the development of chemical tools with potential diagnostic and therapeutic clinical applications through their optical and magnetic resonance signals. His scientific work bequeathed a lasting wealth of chemical tools invaluable for physiological investigation with both current and future applicability.