Project Leaders:   
B. Brett Finlay, Robert C. Brunham, Neil E. Reiner

Involved Institutions:   
University of British Columbia, BC Centre for Disease Control, Vancouver Coastal Health Research Institute (VCHRI)

Technology Applications:   
Vaccine and therapeutic development

GE³LS Activity:   
Understanding the Role of Experts in Risk Communication

Research Funding Program:   
Translational Program for Applied Health

Project Website:   
www.prepare.med.ubc.ca

As a global community, we are constantly waging battles to combat infectious diseases that threaten health and reduce productivity. Despite outstanding historical successes such as the elimination of smallpox, the near elimination of polio, and the introduction of many highly effective vaccines, battles against infectious diseases continue to be fought. Emerging and re-emerging infectious diseases (EID) such as BSE, SARS, pathogenic E. coli, and Clostridium difficule have recently dealt serious blows to Canada. Urban centres are particularly vulnerable to EID because they are densely populated and new pathogens can arrive via international airports and seaports. Due to the diversity and unpredictable nature of EID, intellectual and technological resources have to be organized in a new way to facilitate effective responses and scientific solutions. This project will do this with interdisciplinary, translational research, reflected in its alternative name: the PRoteomics for Emerging PAthogen Response (PREPARE).

PREPARE is an integrated research program that will use new bioinformatics and computational strategies on genomic and proteomic data to identify new targets in microbial pathogens, ultimately developing both drugs and vaccines. The research will focus on EID pathogens of great public health importance, including the model organisms of methiciliin resistant Staphylococcus aureus, Salmonella enterica (serovar Typhinurium), enterohemorrhagic E. coli and Chlamydia trachomatis.

PREPARE will identify microbial therapeutic targets by studying protein interaction networks at the proteome level. They will also examine insertions/ deletions in the genes of essential microbial proteins and the mechanism of pathogen mimicry of host proteins. These approaches should develop a short list of drug targets for industry that may become the basis for small molecule drug development.

PREPARE also plans to develop vaccine targets by identifying proteins that are processed and presented on major histocompatibility molecules by dendritic cells. They will use a novel immunoproteomics approach, where ultra-sensitive mass spectrometry will identify a complete list of T cell antigens on a genome wide scale for an intracellular pathogen. These processed proteins may be used as molecular vaccines to elicit protective T cell immunity.

Genomic expertise provides the foundation for rapid response science and will strengthen Canada’s preparedness for emerging infectious diseases. The proposed research will create novel developmental pathways that can change approaches to vaccine and therapeutic development.