Sir Tim Hunt: Switches and Latches

Sir Tim Hunt studied Natural Sciences at Cambridge and later joined the Department of Biochemistry where he completed a PhD on the synthesis of haemoglobin. He won a Nobel Prize in Physiology or Medicine in 2001 for the discovery of cyclins – proteins that regulate mitosis, and was awarded a Royal Medal by the Royal Society in 2006. His lecture at Oxford was a story of collaborations, inspiring conversations, simple answers to complicated problems and endless questions.

The cell cycle is regulated by three key switch points which decide whether the cell is prepared to enter mitosis. There  are numerous switches in our cells, irreversibly turning on and off different functions. They are responsible for  “careful decision making, but absolute commitment”. Sir Tim Hunt was particularly interested in when and how the  switches occur.

Studying frog and clam zygotes, he discovered an interesting trend in protein synthesis: Upon fertilisation, eggs  commence dividing, accompanied by intense protein synthesis. However, cells also begin making three new major  proteins that have not been previously produced. If their synthesis is inhibited, cell division is curtailed.

Tim Hunt then moved on to study the differences in protein synthesis in properly fertilised eggs and eggs fertilised  through parthenogenesis (a type of asexual reproduction). One day he lit upon a disappearing protein, which he  named cyclin. While the production of other proteins increased, that of cyclins rose at first and then faded away. Later  that day, whilst having dinner with his friend John Gerhart, he heard about MPF.

Maturation Promoting Factor, or MPF, is a protein enzyme which catalyses cell division, and had been discovered some years earlier by a group of Japanese scientists. This enzyme was present in high concentration in M-phase and low concentrations in interphase, but could not be purified. It was detected first in frog oocytes, starfish and later in humans. Tim Hunt realised that cyclin explained the behaviour of MPF. Their periodic oscillations were similar. Cell division is controlled by synthesis which switched it on and breakdown which switched it off. Cyclin is synthesised, MPF is turned on and mitosis takes place. Then cells degrade cyclin which inactivates MPF and the cell exits mitosis. “It was a simple hypothesis that I didn’t even dare to believe because it was too good to be true.” We now refer to MPF as cyclin-dependent kinases.

Scientists are nowadays trying to identify the role of the Greatwall kinase and its affect on phosphatase in the cell cycle – a project that Tim Hunt and his team began but did not successfully finish. As Sir Hunt, himself, said: “There’s not end to questions.”

The last slide of the presentation was a quote by Isaac Newton: “You know, the proper Method for inquiring after the properties of things, is to deduce them from Experiments.” And that’s the one thing Sir Tim Hunt would like people to remember from his lecture: “Do experiments!”

Image: “Tim Hunt at UCSF 05 2009 (3)” by Masur – Own work. Licensed under GFDL via Wikimedia Commons – http://commons.wikimedia.org/wiki/File:Tim_Hunt_at_UCSF_05_2009_(3).jpg#mediaviewer/File:Tim_Hunt_at_UCSF_05_2009_(3).jpg