New Scholar Award in Global Infectious Disease
Ernesto Abel-Santos, Ph.D.
Albert Einstein College of Medicine of Yeshiva University

Peptide Modulators of Bacterial Cell Differentiation

The continuous threats of bioterrorism, combined with the appearance of multi-drug resistant infections, have created the need for the development of new antimicrobial treatments. Peptides have been used successfully to treat diseases ranging from cancer to infections, but their use has been limited by instability towards cellular catabolism. Cyclization affords a way to stabilize peptides, thus allowing the search for inhibitors of biological targets. My laboratory is using the intracellular production of cyclic peptides to cause phenotypic changes in microbial cells in order to bridge the gaps between genomic information, essential enzymatic function, and antibiotic design. 

This project will develop new genetic systems to simultaneously identify proteins involved in Bacillus subtilis spore germination (or vegetative cell sporulation) and peptides that modulate their activity. The research plan will require screening intracellular peptides libraries for molecules that inhibit spore germination or activate vegetative cell sporulation. Once peptides able to modulate cell differentiation have been identified, co-expression of a genomic library will allow the recovery of the targeted biological function(s). After the identity of a cell differentiation protein has been revealed, reverse functional complementation will permit the detection of every peptide able to modulate its activity. The family of peptides so obtained will provide the structure activity data necessary to understand the chemical and functional determinants of peptide-protein interactions.

Contact Dr. Abel-Santos.