Research Highlights

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This project generates rationally designed and engineered lipid A structures (TLR4 Ligands) with altered pro-inflammatory responses via expression of heterologous lipid A biosynthetic enzymes, a process termed BECC (Bacterial Enzymatic Combinatorial Chemistry). Individual lipid A structures are tested for adjuvant potential in a variety of in vitro and in vivo models. Two BECC molecules are currently part of the NIAID Adjuvant Development Program to formulate and evaluate each for IND enabling testing with three established immunogenic vaccine antigens.

The major goal(s) of the project is to establish a rapid, small scale extraction procedure for lipids isolated from the membranes of Gram positive and negative bacterial and fungal species for rapid identification that can also be used as a potential diagnostic to improve patient outcomes. Through work with various collaborators, the Ernst lab has identified the lipid structures of various pathogenic and environmental bacterial species. All these structures are continuously added to a growing reference library of lipids. On-going goals for this work include the ability to reliably extract bacterial and fungal lipids direct from patient samples.

This project uses genetic, molecular biology, and analytical approaches to define biosynthetic genes and regulatory mechanisms required for the synthesis of cystic fibrosis-specific lipid A modifications in Pseudomonas aeruginosa. The Ernst lab continues to investigate the unique environment of the CF lung using mass spectrometric imaging to identify the unique inflammatory properties and structural regulation of P. aeruginosa lipid A in vivo.