Understanding Signalling in Cyanobacteria

Supervisors: Professor Marcel Jaspars and Dr Wael Houssen

Cyanobacteria synthesise a wealth of toxins, the most studied of which are the microcystins with over 60 variants. Microcystins are potent inhibitors of protein phosphatases 1/2A, which can result in a range of clinical symptoms. Cyanobacteria often produce dense growths, known as blooms, which are a threat to livestock, and microcystins released into the water supply have resulted in human fatalities. Microcystins can also cause chronic effects due to their action as tumour promoters and it is thought that their presence in drinking water increases the risk of primary liver cancer. Little is known about the advantages of microcystins to the producing organism, Microcystis aeruginosa, or the ways in which their production may be modulated in their native environment. Such information would be very useful in furthering understanding and management of toxic blooms. This will be of major benefit for water resource management and maintaining a safe drinking water supply for humans and livestock.

In this PhD studentship, we aim to modulate transcriptional activation of the microcystin gene cluster using small molecules. The work is based around a small molecule (Microcystin Induction Factor, MIF) produced by the cyanobacterium Planktothrix agardhii which increases toxin content in M aeruginosa. We discovered and partially characterised MIF during previous work.1 The structure of MIF could not be fully defined in 2003 as sufficiently powerful spectroscopic methods had not yet been developed. M aeruginosa and P agardhii often co-occur in temperate freshwater bodies with P agardhii being an early coloniser and M aeruginosa appearing subsequently. We also discovered that a related molecule, aeruginosamide, isolated from a toxic bloom containing both P agardhii and M aeruginosa was able to reduce toxin production in M aeruginosa significantly.2 The gene cluster for the production of microcystins has been reported previously, but it has only been recently that the biosynthesis of aeruginosamide-like molecules has been defined at a genetic level.3 Given our evidence showing the likely role of such molecules in interspecific signalling and the availability of both relevant gene clusters, the time is now ripe to investigate this important aspect of chemical ecology using the tools of molecular biology.