Education:

1. Wet electrostatics and biomolecular self-asemblyGerard C. L. Wong, University of Illinois at Urbana Champaign, DMR-0409769 Antimicrobial peptides (AMP’s) are cationic amphiphiles that comprise a key component of innate immunity. Synthetic analogues of AMP’s recently demonstrated broad spectrum antimicrobial activity, buy the underlying molecular mechanisms are unknown. Unlike AMP’s, these synthetic molecules are often too small to span the membrane, so the mechanisms are likely different. Using synchrotron x-ray scattering and confocal microscopy, we show how a prototypical class of synthetic antimicrobials based on phenylene ethynylene induce pore forming reconstructions in membranes. Moreover, we show that these antimicrobials target phosphoethanolamine (PE) lipids, which are typically found in high concentrations in bacterial membranes but not in mammalian membranes (Yang et al., JACS 2007) Electron density (top) of self assembled phase of bacteria killing peptides and membranes (bottom). Note the hexagonal arrangement of water channels.

2. Wet electrostatics and biomolecular self-asemblyGerard C. L. Wong, University of Illinois at Urbana Champaign, DMR-0409769 Education: Researchers with a diverse range of backgrounds contributed to this research program. This research includes contributions from 3 undergraduates (Matthew Davis, Daniel Parente, and Clarabelle de Vries), 2 graduate students (Lihua Yang and Abhijit Mishra) and 1 post-doc (Vernita Gordon). One of the undergraduates above is a co-author on the JACS paper describing this work. The other two undergraduates will be co-authors in a future paper. The idea of this work came from my participation in a NSF sponsored exchange program in NanoBiotechnology with Japan, in which 12 US Assistant Professors and 12 Japanese Assistant Professors engaged in reciprocal visits. Societal Impact: The development of bacterial resistance to our best antibiotics is an urgent problem in human health. The 2003 NNIS Report shows double-digit increases in antibiotic-resistant strains over a course of 5 years. In this work, we elucidated how a class of synthetic antimicrobials specifically target bacterial membranes but not mammalian membranes. By understanding the ‘design rules’ of synthetic membrane active antimicrobials, we make it possible to generate a large number of new antibiotics to mitigate the problem of bacterial resistance.