Cyanobacteria Harness Pulse Amplitude Modulation to Control Biological Functions

Cyanobacteria, an ancient lineage of bacteria that perform photosynthesis, have been found to regulate their genes using the same physics principle used in AM radio transmission. 

New research published in Current Biology has found that cyanobacteria use variations in the amplitude (strength) of a pulse to convey information in single cells. The finding sheds light on how biological rhythms work together to regulate cellular processes. 

In AM (amplitude modulation) radio, a wave with constant strength and frequency - called a carrier wave - is generated from the oscillation of an electric current. The audio signal, which contains the information (such as music or speech) to transmit, is superimposed onto the carrier wave. This is done by varying the amplitude of the carrier wave in accordance with the frequency of the audio signal. 

The research team, led by Professor James Locke at the Sainsbury Laboratory Cambridge University (SLCU) and Dr Bruno Martins at the University of Warwick found that a similar AM radio-like mechanism is at work in cyanobacteria. 

In cyanobacteria, the cell division cycle, the process through which one cell grows and divides into two new cells, acts as the 'carrier signal'. The modulating signal then comes from the bacteria's 24-hour circadian clock, which acts as an internal time-keeping mechanism.

This finding answers a long-standing question in cell biology – how do cells integrate signals from two oscillatory processes - the cell cycle and the circadian rhythm – which operate a different frequencies? Until now, it was unclear how these two cycles could be coordinated. 

To solve the puzzle, the research team used single-cell time-lapse microscopy and mathematical modelling. With the time-lapse microscopy, they tracked expression of a protein, the alternative sigma factor RpoD4. RPoD4 plays an important role in the initiation of transcription, which is the process by which genetic information from DNA is transcribed into RNA. The modelling allowed researchersto explore signal processing mechanisms, comparing modeling results with microscopy data. The team found RpoD4 is turned on in pulses that occur only at cell division, which made it an ideal candidate for tracking. 

We found that the circadian clock dictates how strong these pulses are over time. Using this strategy, cells can encode information about two oscillatory signals in the same output: information about the cell cycle in the pulsing frequency, and about the 24-hour clock in the pulsing strength. This is the first time we've observed a circadian clock using pulse amplitude modulation, a concept typically associated with communication technology, to control biological functions." 

Dr. Chao Ye, Lead Author

"Varying the frequency of either the cell cycle, through ambient light, or the circadian clock, through genetic mutations, validated the underlying principle. It is striking to see examples in nature of what we sometimes think of as 'our' engineering rules," said co-corresponding author Dr Martins. "The cyanobacterial lineage evolved 2.7 billion years ago, and have an elegant solution to this information processing problem." 

Professor Locke added: "One reason we study cyanobacteria is that they have the simplest circadian clock of any organism, so understanding it lays the foundation we need to understand clocks in more complex organisms, like people and crops. 

"These principles could have broader implications in synthetic biology and biotechnology. For example, this could help us develop crops that are more resilient to changing environmental conditions, with implications for agriculture and sustainability."