Current projects and funding:
Development of genetic techniques.
We are developing the next generation of genetic techniques for identifying and validating drug targets. Our work involves the investigation of a number of alternative methods to prove that a given target gene is essential for the bacteria to survive. We are particularly interested in methods of constructing conditionally expressing strains, in which gene expression is either reduced or completely turned off. By constructing such conditionally expressing strains, we will be able to test if genes are essential under a wide range of conditions.
Proteases as drug targets.
Proteases have proven to be attractive drug targets in several disease areas, such as HIV/AIDS, where several protease inhibitors have been developed. We are investigating the possibility that proteases of Mtb may also be useful drug targets. We are using sophisticated genetic techniques to determine which proteases should be selected for intensive study. Our aim is to validate proteases as drug targets and to provide the next step for screening for protease inhibitors with activity against Mtb.
This project is funded by the Global Alliance for TB Drug Development.
We know some of the bacterial targets of the drugs currently used to treat tuberculosis, but we do not understand at all how inhibition of a particular target leads to cell death. Our overall aim is to identify genes involved in cell death in Mtb. This will have relevance to latent infection, persistence and antibiotic tolerance. We will use a genetic approach to identify cell death pathway(s) which are physiologically relevant. Ultimately this will lead to a better understanding of how to kill non-replicating, persistent or "latent" organisms, yielding dividends in TB drug therapy.
This project is funded by the Washington Global Health Alliance.