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Helen Blackwell

Professor Helen E Blackwell

Our laboratory pursues research at the chemistry-microbiology interface. We are deeply interested in the mechanisms by which bacteria sense each other, their environment, and the eukaryotic hosts on which and in which they may reside. One prominent pathway that we study is called quorum sensing, which allows bacteria to assess their local population density and initiate group behaviors at high cell (or “quorate”) density. This pathway allows, for example, many pathogens to amass in large populations prior to attacking their hosts. Bacteria use chemical signals for quorum sensing, and it is the concentration of these signals in a given environment that alerts the bacteria to their current cell number. We are interested in the structures of these signals and how we can reengineer them to either ablate or amplify quorum-sensing networks. Through synthesis and systematic screening, we have identified critical structural features of these signals and non-native functionality that we can install into the signals to tune their function. Thereby, we have developed non-native molecules that strongly inhibit or activate quorum-sensing pathways and modify infection processes. These compounds represent useful tools to explore the role of quorum sensing in many biological processes. We are applying them to both study fundamental aspects of quorum sensing pathways, and examine different types of infections in animals and plants.

Blackwell Group Website

For recent articles from the Blackwell group:

1.
Geske GD, O'Neill JC, Miller DM, Mattmann ME, Blackwell HE. 2007. Modulation of Bacterial Quorum Sensing with Synthetic Ligands:  Systematic Evaluation ofN-Acylated Homoserine Lactones in Multiple Species and New Insights into Their Mechanisms of Action. J. Am. Chem. Soc.. 129(44):13613-13625. http://dx.doi.org/10.1021/ja074135h
2.
Stacy DM, Welsh MA, Rather PN, Blackwell HE. 2012. Attenuation of Quorum Sensing in the PathogenAcinetobacter baumanniiUsing Non-nativeN-Acyl Homoserine Lactones. ACS Chem. Biol.. 7(10):1719-1728. http://dx.doi.org/10.1021/cb300351x
3.
Welsh MA, Eibergen NR, Moore JD, Blackwell HE. 2015. Small Molecule Disruption of Quorum Sensing Cross-Regulation inPseudomonas aeruginosaCauses Major and Unexpected Alterations to Virulence Phenotypes. J. Am. Chem. Soc.. 137(4):1510-1519. http://dx.doi.org/10.1021/ja5110798
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