Actinobacteria Metabolic Engineering
This group is located at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)
The growing resistance towards established antibiotics presents a serious problem especially with infectious diseases. The development of new drugs is mainly based on known molecules and mechanisms, which allows bacteria to assimilate rapidly. Hence, scientists are looking for novel drugs. At the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), a branch of the Helmholtz Centre for Infection Research (HZI) at Braunschweig, the researchers develop new pathways, by which they force actinomycetes to produce hitherto unknown compounds.
Actinomycetes are a well-known and very intensively examined group of bacteria. They have produced various antibiotics and antitumor drugs and are industrially used to produce antibiotics and agro chemicals. Despite them being thoroughly studied, a huge potential remains still to be revealed. The scientists at HIPS focus on the unused genes of the bacteria. These “silent genes” potentially contain the genetic information for new drugs. Researchers therefore expect to find different interesting natural products after activating such clusters.
The concept to find and wake up such silent gene cluster is already used with different microorganisms. However, to activate silent genes in actinomycetes is especially demanding. Some of the strains cannot be manipulated at all by conventional techniques. They immediately remove unknown material from the cells. To circumvent this defence mechanism, the specialists for metabolic engineering have developed a new technology. They incorporate artificial transposons, so-called jumping genes, into the actinomycetes. To use transposons for the genetic manipulation of bacteria is also common, but the kind of transposon the Saarbrücken researchers work with is new. The transposons are not generated from bacteria but assembled synthetically. In the genome of the actinomycetes, they function as random generator for mutations and switch genes randomly on and off. The newly generated metabolic compounds or functionalities, which are switched off in the mutant, can be assigned to specific genes.
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