We propose to apply new proprietary computational methods to assign biological functions to novel proteins in the genome of Mycobacterium tuberculosis, the causative agent of TB. Traditional computational methods can only assign functions to genome sequences that are homologs of other previously characterized proteins. The new algorithms developed by Protein Pathways scientists use other types of information, derived from trans-genome analyses, to assign functions to proteins that cannot be characterized by traditional computational methods. The methods will assign probable functions to as many as 1,000 uncharacterized TB protein sequences. Many of these proteins will be identified as having roles in virulence and will therefore be attractive targets for future drug development efforts.
The world-wide emergence of multi-drug resistant strains of many common pathogens calls for new antibiotics. The work proposed here will identify the functions of many previously uncharacterized proteins in the genomes of serveral pathogens, including Staphylococcus aureus and Enterococcus faecalis. Those with roles related to virulence will serve as new, previously unknown targets for therapeutic drugs. Once experimentally validated, these targets will be marketed to our pharmeceutical customers and partners.
