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Keep Nibbling at the Edges

P. Cohen

Published 2009 in Journal of Biological Chemistry

ABSTRACT

A lifelong passion for natural history and an aptitude for chemistry had led me to study for a B.Sc. in biochemistry at University College London (UCL) from 1963 to 1966. It was during this period that the allosteric theory of enzyme regulation was put forward by Jacques Monod, Jean-Pierre Changeux, and Francois Jacob at the Institute Pasteur. This explained how the end products of a biosynthetic pathway exerted feedback control on the enzyme catalyzing the initial and rate-limiting step. Reading these papers sparked an interest in enzyme regulation and led me to become a graduate student in the UCL laboratory of Michael Rosemeyer, with whom I had carried out a short undergraduate project the previous year. Michael had offered a project to study the control of glucose-6-phosphate dehydrogenase, the first enzyme in the pentose phosphate shunt. I purified Glu-6-P dehydrogenase and determined its subunit composition (1, 2) because the “quaternary structure” of an enzyme was thought to be key to how it was regulated by allosteric effectors. The project gave me an excellent grounding in protein chemistry, but Glu-6-P dehydrogenase seemed merely to be regulated by the NADPH/NADP ratio, and it was clear that I needed to find a more challenging problem to work on. The idea of applying to Edmond (Eddy) Fischer for a postdoctoral position arose during a discussion with Prakash Datta, a professor in the department at UCL, and Bill Whelan, the Chairman of Biochemistry at the University of Miami. Bill had just founded FEBS Letters and had come to visit because Prakash had become the first Managing Editor of the journal. I had heard Eddy Fischer give several lectures at a protein chemistry summer school in Venice in 1967, and so Bill, who was a friend of Eddy, agreed to write a letter of support to accompany my application. However, my initial approaches were unsuccessful, and only after I had obtained a UK Science Research Council (subsequently renamed the Biotechnology and Biological Sciences Research Council) postdoctoral fellowship funded by NATO did Eddy agree to let me come. To this day, I therefore always re-evaluate very carefully persistent postdoctoral applicants who will not take no for an answer!

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