WASHINGTON - Two studies conducted by scientists at Dartmouth Medical School have provided significant insights into why the 24-hour body clock does not change with temperature when metabolism is so affected.

Circadian systems are biological oscillators that orchestrate activities through an elaborate network of interactive proteins and feedback loops. They depend upon transfer of phosphate groups, called phosphorylation, to clock proteins for setting the 24-hour cycle.

Drs. Jay Dunlap and Jennifer Loros, who led both studies, have revealed that both studies looked at phosphorylation of the frequency (FRQ) clock protein, a central feedback cog in the fungal clock system.

They have documented the workings of FRQ and most other components in the Neurospora clock.

“The Cell paper describes how the cell uses phosphorylation of a clock protein to keep the period length of the cycle close to the same across a range of temperatures. This phenomenon, called temperature compensation, is one of the few canonical properties of rhythms that still lack molecular description,” said Dunlap.

The researchers say that their research suggests a new role for the clock-associated enzyme, casein kinase (CK)2, as a key control for temperature compensation. They pursued two uncharacterised circadian protein mutants shown to affect compensation in an unusual way, and identified different subunits of the same enzyme, CK2.

The team developed new ways to manipulate the genome, and showed, by controlling expression, that the level of CK2 dictates the form of compensation through the phosphorylation of the clock protein FRQ.

According to them, the property is unique to CK2 and shared with none of the other similar enzymes implicated in clock function.

The second study traced protein interactions throughout the cycles to show how phosphorylation controls circadian rhythm. It pinpointed a near record number of modifications on FRQ and described how each appears and disappears over the day.

The researchers identified interacting proteins to track and correlate changes in the core circadian network. They determined the clusters and locations of known sites, and through mutational analysis identified novel functional domains to create a dynamic view of a clock protein in action.

The two study have been published in the journal Cell. (ANI)