PhD ceremony mr. M.H. Medema: Medicines from microbes. Exploiting the power of computational genomics for natural products discovery and engineering
| When: | Fr 27-09-2013 at 11:00 |
PhD ceremony: mr. M.H. Medema, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen
Dissertation: Medicines from microbes. Exploiting the power of computational genomics for natural products discovery and engineering
Promotor(s): prof. E. Takano, prof. R. Breitling, prof. L. Dijkhuizen
Faculty: Mathematics and Natural Sciences
Bacteria, fungi and plants produce large numbers of small but complex molecules called ‘secondary metabolites’, a range of which is applied medicinally as antibiotics, chemotherapeutics, cholesterol-lowering agents and immunosuppressants. There is great need to find more such metabolites, especially because many bacteria are becoming resistant to the antibiotics that are currently used in the clinic. However, the rate at which new secondary metabolites are being discovered has stalled in recent decades.
To overcome this problem, we developed a strategy to discover new secondary metabolites more efficiently. This strategy exploits the enormous amount of genetic information from all sorts of organisms that has recently become available: we wrote computer programs to efficiently mine this genetic information to predict what kind of secondary metabolites organisms can make, just based on the information encoded in their DNA. Instead of being limited to studying individual organisms one at a time in a relatively random fashion, this allowed us to systematically search through thousands of organisms to identify a vast array of systems that produce metabolites with pharmaceutical potential.
To make it possible to explore this rich potential experimentally, we outline a synthetic biology approach to characterize the molecules produced by these systems in high throughput. The innovative part of this approach is that the systems can be redesigned from scratch on a computer. This redesign makes it possible to insert them into bacteria that have been specifically engineered to be proficient in synthesizing the corresponding metabolites.
Taken together, the combined application of informatics and synthetic biology experimentation holds great promise to reinvigorate drug discovery from the molecules of nature.