Symposium on Proteomics and Toxicology

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

Description (provided by applicant) This proposal is a request for financial support for a half-day symposium on "Proteomics and Toxicology: Recent Advances in Technology and Applications" to be presented at the American Chemical Society National Meeting, New York, New York, September 7-11th, 2003. Completion of the human and mouse genome projects has stimulated new approaches to understanding the role of environmental chemicals on human health and alternative approaches to understanding toxicological effects of environmental chemicals and pharmaceuticals. Proteomics is at the forefront of the new technologies that are emerging. Recent studies have already provided insights into the mechanisms of action of a wide range of substances, from metal to peroxisomal proliferators. The use of 2-D gel and mass spectrometry to measure simultaneously a number of proteins in a sample offers the possibility of identifying relationship between changes in protein expression and toxicity from environmental chemicals and drugs. For example, studies in rates have identified novel proteins in serum that may be markers of renal toxicity. Proteomics has significant advantages over gene expression profiling. Proteins can be measured reliably in a broader range of biological tissues (blood, CSF, synovial fluid, urine) than mRNA transcripts. Furthermore, the proteins that are identified present the ultimate cellular that are upregulated rather than some intermediate in the toxicological process. A current limitation is the difficulty in detecting proteins that are expressed in low abundance in biological fluids. Considerable evidence supports a key role for protein adducts in adverse effects of chemicals. Limitations in analytical technology have slowed progress in this area. New applications of liquid chromatography-tandem mass spectrometry now offer the potential to identify protein targets of reactive electrophiles and to map the adducts at the level of amino acid sequence. These approaches can map adducts to specific amino acids in protein targets and are being adapted to searches for protein adducts in complex proteomes. Ultimately, these tools will facilitate the identification of new biomarkers of environmental chemical exposure and permit new mechanistic studies to be conducted. Such studies will help to elucidate the precise pathways by which protein modifications contribute to the adverse effects of exposure to environmental chemicals and drugs. Based on previous experience, it is anticipated that in excess of 200 investigators will attend the symposium. The goal of the proposed symposium is to provide an update on both the technology and applications of proteomics to a wide range of researchers working in the field of toxicology. They will then be able to apply the tools that are presented at the symposium to their own research projects. The speakers have been carefully chosen because they are experts in their own particular area of proteomics. The symposium will maintain a balance approach between descriptions of new technology and the application of that technology. Therefore the attendees will be given an insight into how modern methods of proteomics can be brought to bear on important problems in toxicology. It is anticipated that the symposium will also provide the opportunity to introduce new investigators to the field.