Ribosome distribution key to programming cells

By controlling the distribution of bacterial ribosomes, synthetic biologists say they can program cells to produce new drugs.

Led by work at the University of Warwick and University of Surrey, new research has suggested that dynamically managing the allocation of essential resources inside engineered cells can increase the potential of synthetically programming cells to combat disease and produce new drugs.

José Jiménez, Lecturer in Synthetic Biology at the University of Surrey's Faculty of Health and Medical Sciences said: “The ultimate goal of the selective manipulation of cellular functions like the one carried out in this project is to understand fundamental principles of biology itself. By learning about how cells operate and testing the constraints under which they evolve, we can come up with ways of engineering cells more efficiently for a wide range of applications in biotechnology.”

The team have developed a way to efficiently control the distribution of ribosomes – the ‘factories’ inside cells that build proteins that keep the cell alive and functional – to both a synthetic circuit and the host cell. Synthetic circuitry can be added to cells to enhance them and make them perform bespoke functions. A cell only has a finite amount of ribosomes, and the synthetic circuit and host cell in which the circuitry is inserted both compete for this limited pool of resources. It is essential that there are enough ribosomes for both, so they can survive, multiply and thrive. Without enough ribosomes, either the circuit will fail, or the cell will die – or both.

Using the engineering principal of a feedback control loop, the researchers have developed and demonstrated a system through which control can be exerted over the distribution of ribosomes. When the synthetic circuit requires more ribosomes to function properly, more will be allocated to it, and less allocated to the host cell, and vice versa.

Declan Bates, Professor of Bioengineering at the University of Warwick’s School of Engineering and Co-Director, Warwick Integrative Synthetic Biology Centre (WISB) said: “Synthetic Biology is about making cells easier to engineer so that we can address many of the most important challenges facing us today - from manufacturing new drugs and therapies to finding new biofuels and materials. It’s been hugely exciting in this project to see an engineering idea, developed on a computer, being built in a lab and working inside a living cell.”