Biochemical Journal Young Investigator Award winner

Erin Willert

Erin Willert received her BS in Chemistry at the University of Texas at Austin in May 2002. Erin attended graduate school at the University of Texas Southwestern Medical Center at Dallas, working with Dr Margaret A. Phillips, and received her PhD in March of 2008. Erin will begin her postdoctoral position with Dr Herbert W. Virgin IV at Washington University in September of 2008.

Trypanosoma brucei causes African trypanosomiasis, a fatal and neglected disease. In trypanosomes, the biosynthesis of polyamines, which are essential cellular cations, is uniquely conjugated to redox balance, as spermidine links two glutathione molecules to produce the novel redox cofactor trypanothione. S-adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in this pathway. Erin has discovered that T. brucei AdoMetDC is allosterically activated by a novel protein that we named prozyme¹. The prozyme gene is only found in the trypanosomatid species, and arose by gene duplication and mutational drift from the canonical AdoMetDC. The regulation of AdoMetDC activity by prozyme highlights a species-specific difference between the parasite and its human host. Erin’s work has demonstrated that the AdoMetDC/prozyme heterodimer is important in the biosynthesis and regulation of trypanothione and polyamines, and highlights this complex as an attractive drug target.

1. Willert, E. K., Fitzpatrick, R. & Phillips, M. A. (2007) Allosteric regulation of an essential trypanosome polyamine biosynthetic enzyme by a catalytically dead homolog. Proc. Natl. Acad. Sci. U.S.A. 104, 8275-8280.