Camilla A Mauzy

Air Force Research Laboratory Integrated Omics Research

Integrated Omics research capabilities within the Air Force Research Laboratory began in 2003 with the initiation of a Defense Technology Objective project aimed to identify biomarkers of toxicity occurring within the warfighter as a preclinical indicator. Current methods for determining toxic exposures are not responsive enough or created available for deployment to prevent serious health effects. Using Integrated Omics (Genomics/Epigenetics, Proteomics, and Metabonomics) for biomarker discovery, we have identified specific molecular markers which, once validated, could be used for real-time or near-real-time monitoring of the human response to uncharacterized exposures. The determination and use of validated biomarker sets, when installed on a fieldable biomonitor system, could allow fast determination of subclinical organ damage in response to chemical exposures. Since initiation of this program, our group has applied Omics technologies for biomarker discovery in a number of toxicology and human performance projects, including jet fuel exposures and cognitive fatigue.

Identifying Potential Protein Targets for Toluene Using a Molecular Similarity Search, in Silico Docking and in Vitro Validation

The toxicity of chemicals greatly depends on their interaction with macromolecular targets. The main goal of this study was to develop an approach for predicting protein targets for chemical toxins using a molecular similarity search of toxin–target information collected in the Toxin and Toxin-Target Database. The developed method was used to identify new targets for toluene which could predict potential cellular toxicity and to validate the approach with in vitro laboratory studies. We obtained 124 potential targets for toluene from a molecular similarity search. Results were further analysed using in silico molecular docking methods. The binding of toluene to two proteins, hemoglobin and serum albumin, was validated by the measurement of binding using microscale thermophoresis. The measured binding constant between toluene and hemoglobin was 1.9 μM, while albumin demonstrated toluene-induced aggregation. These results demonstrate the applicability of an exploratory in silico toxicity tool, based on a molecular similarity search and protein–ligand docking, for identification of potential targets for chemical toxins.