Ticking of biological clock unravelled
A variety of organisms such as fungi, plants, fruit flies and people have a day and night rhythm that sees to specific activities, like sleeping and eating, will occur only at specific moments of the day. This rhythm is being driven by a biological clock within the cell. Such clocks are ticking during a period of about twenty-four hours without needing any outside signals. However, in everyday life the biological clock adjust to the rhythm from sunrise to sunset. We experience this synchronizing of the body clock, say, as a jetlag when travelling by air between the continents. Researchers at the FOM Institute for Atomic and Molecular Physics (AMOLF) and the Vrije Universiteit have now developed a model, describing the working of the biological clock of a so-called cyanobacterium. In a combination of three clock proteins one of the proteins in this bacterium is marked at night with a phosphate group, causing this protein immobilizing all activities in the cell. The results of the model that describes this combination mathematically, correspond excellently to the available experimental observations. The researchers will have their findings published in the Proceedings of the National Academy of Sciences (PNAS) of 1 May 2007.
For a long time researchers have thought that bacteria were too uncomplicated to have day and night rhythms too. Therefore, it was quite a surprise when almost twenty years ago appeared that cyanobacteria- a significant group of bacteria that put their energies out of the sunlight - indeed have a similar biological clock as multicellular organisms. The clock in cyanobacteria is made by a biochemical network of three clock proteins that react to one another, KaiA, KaiB and KaiC. KaiC is phosphorylated during a period of one day, a process at which a protein is marked with a phosphate group. Only during the night most of the KaiC proteins have been phopherylated and is KaiC able to immobilize almost all activities in the cell.
Although the biological clock of cyanobacteria is probably independently evolved on that of other organisms, it was suspected that their clocks actually do work in the same way: namely, by controlled production and destruction of clock proteins. However, to everyone’s surprise it appeared from recent experiments that the 24 hours rhythm in phophorylation of KaiC can be reproduced by combining the three clock proteins in a test tube. This was a spectacular result, not only because the Kai system is now one of the first biochemical networks that can be obtained in working order outside the cell in a test tube, but also because it showed that the quantity of clock proteins does not change and that a fundamentally other mechanism has to be responsible for the working of the clock. However, it was not known so far how the interactions between the three clock proteins would lead to a biological clock.
Researchers at the FOM Institute AMOLF and the Vrije Universiteit Amsterdam have now developed a mathematical model that describes how the functioning of the biological clock can be explained from the already known characteristics by experiment of the three clock proteins. In this model every KaiC protein separately goes to a phosphorylation cycle. KaiA and KaiB take care of the cycles that all KaiC proteins are being in line with one another by having the surviving KaiC proteins run faster and by slowing down the ones that run in front in their cycles. Eventually, this will lead to a 24 hours rhythm in KaiC phosphorylation that has been perceived in the test tube. In addition, this model provides for a natural explanation on the phenomenon of temperature compensation - the characteristic of all known biological clocks that they are not running faster or slower significantly when the surrounding temperature changes. So far, this phenomenon had not been accounted for on also other biological clocks.
For more information, please contact dr. Pieter Rein ten Wolde, FOM Institute AMOLF, phone: 020 608 1234; email: tenwolde@amolf.nl
The article is entitled 'An allosteric model of circadian KaiC phosphorylation', the authors are Jeroen van Zon (Imperial College, London), David Lubensky (VU) and Pim Altena and Pieter Rein ten Wolde (AMOLF). The article will be published on 23 April 2007 in an online version of PNAS and on 1 May 2007 in print.