United States Army Medical Research Institute of Chemical Defense
The Center for Catalytic Bioscavenger Medical Defense Research

Project 1 Rational Design of HuPON1 Mutants
Directed by Dr. David Lenz of The United States Army Medical Research Institute of Chemical Defense, project 1 employs rational design based upon homology modeling studies and site directed mutations of specific amino acid residues of PON 1 which in its wild type form has been shown to catalyze the hydrolysis of a variety of nerve agents such as GD, GB and VX.


Project 2 Molecular Evolution of Human Butyrylcholinesterase for Nerve Agent Detoxification
Human Biomolecular
Research Institute
Directed by Dr. Jun Zhang of the Human Biomolecular Research Institute (HBRI), project two focuses upon re-engineering HuBuChE. Combining cutting edge molecular biology techniques, rationally directed mutagenesis, error-prone PCR, and gene shuffling, to generate a diversified huBuChE mutation library which is screened for variants that are both resistant to OP inhibition and that hydrolyze OP analogues.


Project 3 Gene Shuffling of PON1
The Weizmann Institute
Directed by Dr. Dan Tawfik of the Weizmann Institute of Science in Israel, project three applies directed evolution via gene shuffling techniques to generate mutant libraries of PON 1, which is screened using a proprietary throughput assay system selecting for enhanced OP catalytic activity, the technology has been shown to be successful in concept and has been adapted for the next generation of human PON mutants.


Project 4 Computational & Bio-Organic Chemistry of Catalysis
Department of Chemistry
The Ohio State University
Led by Dr. Christopher Hadad of The Ohio State University (OSU), project four focuses on the elucidation of the mechanism of hydrolysis of nerve agents by serine or non-serine active-site-containing human proteins via physio-chemical studies of chemical agents, and spectroscopic characterization of binding domains and catalytic processes, protein structure and in silico modeling, QSAR, and X-ray crystallography.

The data generated drive Path One efforts to design human wild-type protein mutations capable of enhancing catalytic activity against nerve agents.


Project 5 Plant Expression of Recombinant Enzymes
The Biodesign Institute of
Arizona State University
Directed by Dr. Tsafrir Mor of the Arizona State University Institute of Biodiversity, project five genetically engineers tobacco plants to express the protein mutant candidates.


Project 6 Micro Algae Expression of Recombinant Enzymes
Department of Plant,
Cellular and Molecular
The Ohio State University
Led by Dr. Richard Sayre of OSU, project six uses cell wall-less strains of Chlamydomonas micro-algae as a platform to produce mutant human protein candidates.