Interfering with Multicellularity
The social amoeba Dictyostelium discoideum typically preys on bacteria, yet it can also serve as a food source for the related dictyostelid D. caveatum. This feature was first described 30 years ago and has since been subject to further investigations. Importantly, D. caveatum can only feed on D. discoideum if the latter is present in a pre-culminant state. Previous studies have shown that D. caveatum secretes a factor that effectively freezes D. discoideum in a pre-culminant state, inhibiting the formation of the multicellular fruiting body and allowing D. caveatum to phagocytose its prey. While preliminary experiments clearly show that a small diffusible molecule is the responsible morphogenesis inhibitor, its structure, biosynthesis, and mode of action remain elusive. We utilize bioassay-guided fractionation to attempt to isolate and elucidate the structure of the small molecule(s) responsible for the inhibition of multicellular development in D. discoideum.
Furthermore, we are interested in glorin, the acrasin (i.e. the metabolite that orchestrates the aggregation of the amoeba) of D. caveatum. Since little is known about the receptor of this signaling molecule, we are constructing chemical probes to address this question.
Besides eukaryotic inhibitors of multicellularity, we are also interested in bacterial nautral prdocuts that have simila effects.
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(2018) The chemoattractant glorin is inactivated by ester cleavage during multicellular development of the social amoeba Polysphondylium pallidum ACS Chem Biol [In press]
(2017) Versatile synthesis of the signaling peptide glorin Beilstein J Org Chem 13, 247-250.