Project Leader:   
Christoph Borchers

Lead Institutions:   
UVic-Genome BC Proteomics Centre, University of British Columbia, University of Alberta

Technology Applications:   
Health, proteomics, technology development

Research Funding Program:
New Technology Development

The emergence of new pathogens, such as the avian flu or SARS virus, along with the development of multi-drug resistance in known pathogens, including multi-drug resistant Staphylococci or Salmonella, and the growing number of patients afflicted with diseases like cancer and diabetes have put an enormous strain on the Canadian health care system. The escalating costs associated with these threats have resulted in an increasing demand for new or more efficient drugs that need to be developed within a decreasing timeframe, using the rational drug design approach.

Aside from the overall time it usually takes to develop a drug before it can be introduced into the market -- usually 10 years -- two major challenges to developing a new drug are the need for high quality structures of the known drug targets, typically proteins; and the lack of instant feedback on the validity of the modeled drug-binding site.

Now that the human genome and several pathogen genomes have been sequenced, and large-scale proteomics projects have been gaining momentum, the rate at which new drug targets are discovered is likely to increase significantly in the next few years. Using the currently available techniques (X-ray crystallography or nuclear magnetic resonance), it typically takes several months or even years to obtain the structure of a single protein. Furthermore, these traditional structural-biology approaches can face significant challenges, including the requirement for crystallization of the protein and the protein-drug complexes, and in particular the analysis of membrane proteins, which are major drug targets.

Bringing together a strong, innovative team with complementary expertise, including: in vitro crosslinking, photo-affinity labeling, and MS analysis of cross-linked products (Borchers); computational processing of mass spectra, database searching, and interpretation of mass spectra of cross-linked peptides; computational protein structure prediction and evaluation of drug-protein interactions. Several industrial partners will enhance key areas that are critical for success.

The results of this collaborative effort will have an impact on rational drug design and development by shortening the time needed to translate information on specific proteins as potential drug targets into lead structures of suitable drugs from years to months, and by allowing the evaluation of a higher number of potential new drug targets within a given time.

Related Links:
Funding Awarded > Tech Dev