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Synthetic biology offers the prospect of modifying living cells to give them new and useful functions, such as to produce the chemical precursors for novel biomedical or other industrial products.
The idea is not new – bacteria and yeast cells have been used in fermentation for centuries – but until now the exploitation of microorganisms in this way has been largely by trial and error. The EU-funded NICHE project generated greater understanding of cellular behaviour as a means to exploit and tailor their activities for industrial uses.
“What we decided to do within the NICHE project was not to focus on a specific pathway or product but to focus on very general properties that are relevant for every cell,” says project coordinator Bert Poolman, of the University of Groningen in the Netherlands.
For example, one of the most studied species of bacteria, E. coli, is widely used as a host for the production of industrially important molecules, including pharmaceuticals.
“Understanding the intrinsic principles that the cell employs to maintain its homeostasis under changing environmental conditions allows us to ‘tame’ the host for optimal production of target products,” Poolman explains. “Our advances in understanding these responses at a molecular and temporal level could improve the design, optimisation and utilisation of bacterial cells for future biotechnological processes.”
A follow-on project, SynCrop, will take the findings from NICHE to demonstrate how bacteria and yeast could be engineered to produce polysaccharides, vitamins and other chemical building blocks, including so-called ‘platform’ chemicals. Ultimately such technologies could be used to replace petroleum as a source of raw materials for plastics and other important synthetic chemicals.
Safety valves
All kinds of molecules – nutrients, ions and water – continually pass in and out of a cell through transporters and channels in the cell membrane. The cell actively controls these routes to maintain internal conditions such as pressure, acidity, ionic concentration and the crowding of molecules – a principle known as homeostasis. When the environment of the cell is perturbed it adjusts its internal conditions to counteract the consequences of this external stress.
Among the highlights of NICHE were discoveries about channels that act as safety valves to prevent the internal pressure becoming too high. Not only are there ten times as many channels as expected but there are seven different types, each opening at a different pressure.
The team also learned how cells can be reprogrammed to produce the proteins needed to make new membrane channels as conditions change.
“This type of information is not only important as basic science but will find its way into technology,” Poolman says.
The project was funded through the EU’s Marie Skłodowska-Curie actions programme, supporting 11 PhD students and two post-doctoral researchers at six European academic institutions and three companies.
The researchers came from the disciplines of biology, chemistry and computational sciences, and the combination of experimental and modelling approaches was key in understanding how cells exchange molecules with their surroundings.
NICHE equipped the young researchers with a broad range of skills gained through exchanges between the collaborating institutions and placements with industrial partners. In particular they learned to appreciate the very different approaches of experimentalists and computer modellers that will stand them in good stead as they move out into industry.
“The multidisciplinary approaches provided the students with a unique training background,” says Poolman. “It allowed us to tackle generic problems in systems and synthetic biology that would not have been possible otherwise.”