Alexander Funk

Personal Data:
Country of Origin: Germany
Start of PhD: February 2006
Institution: HKI

PhD Project:
Regulation of Polyketide Synthase Gene Clusters in Aspergillus nidulans

Supervisor(s): U. Horn (HKI), C. Hertweck (HKI), A.A. Brakhage (HKI)

Abstract:
The availability of fully sequenced fungal genomes has opened the doors to a wealth of information on putative secondary metabolite (natural product) gene clusters. Genome analyses show that surprisingly high numbers of polyketide synthase (PKS) gene clusters exist in filamentous fungi. Up to 28 PKS gene clusters can be assumed in the genome of the well-known model organism Aspergillus nidulans based on in silico analysis. Although recently a few metabolites could be identified, the products of a large number of PKSs remain unknown and less is known about their biological function and regulation. Weak promoter activity and short time of expression make the gene regulation studies challenging.
We use a reporter system based on the marine copepod Gaussia princeps luciferase successfully applied in A. nidulans for measuring single gene activity. The luciferase also contains a secretion signal facilitating extracellular signal detection during various cultivation techniques. In combination with gene knock-out and overexpression strategies as well as protein-DNA interaction studies (surface plasmon resonance) we try to elucidate transcription factor based pathways involved in secondary metabolite regulation. By combining classical continuous cultivation techniques and DNA microarray analysis, we are able to get a global overview on media- and growth phase-dependent regulation.