A direct consequence of the universality of the genetic code is the possibility for genetic information to be transferred between evolutionarily distant species. In the context of genetic engineering, however, this type of genetic spillover is highly concerning. Furthermore, biotechnology will play a central role in addressing pressing challenges in pharmaceutical development, sustainable fuel sources, and efficient carbon fixation. Thus, essential parts of the economy will increasingly rely on bioproduction facilities harboring tailor-made microbes. It is therefore critical that such facilities are extremely reliable. However, due to the universality of the genetic code, engineered organisms susceptible to viral invasion. In fact, a single viral particle that finds its way into a bioproduction facility can force its operational shutdown.

Altering the genetic code of a cell provides an opportunity to render natural and synthetic genetic information incompatible. This breakthrough offers a means to protect the environment from genetically engineered organisms and, vice versa, engineered organisms critical for bioproduction from viral invasion. Through concerted efforts in genome recoding and translational engineering, it was possible to create the first organism with a synthetic genetic code. This organism is genetically isolated; it can neither give nor receive genetic information from the environment.

The lab is continuing to develop altered genetic codes to increase the safety of biotechnology and aspires to rewrite even the most complex biological systems in alternative synthetic genetic codes. Key to this is the development of methodology for the synthesis of entire genomes. To date the genomes of only two bacterial species have been synthesized (Mycoplasma genitalium & E. coli). For the more general application of genetic isolation genome synthesis needs to improve in scope and scale.

PhD students will work on the interface of genome synthesis (method development) and genetic isolation (application).

References

Zürcher, J.F., Robertson, W.E., Kappes, T., Petris, G., Elliott, T.S., Salmond, G.P.C., Chin, J.W. (2022)
Refactored genetic codes enable bidirectional genetic isolation
Science 378(6619): 516-523

Zürcher, J.F., Kleefeldt, A.A., Funke, L.F.H., Birnbaum, J., Fredens, J., Grazioli, S., Liu, K.C., Spinck, M., Petris, G., Murat, P., Rehm, F.B.H., Sale, J.E., Chin, J.W. (2023)
Continuous synthesis of E. coli genome sections and Mb-scale human DNA assembly
Nature 619(7970): 555-562

Fredens, J., Wang, K., Torre, D.d.l., Funke, L.F.H., Robertson, W.E., Christova, Y., Chia, T., Schmied, W.H., Dunkelmann, D.L., Beránek, V., Uttamapinant, C., Llamazares, A.G., Elliott, T.S., Chin, J.W. (2019)
Total synthesis of Escherichia coli with a recoded genome
Nature 569(7757): 514-518