Finding drugs that affect mitochondria.
Mitochondrial dysfunction is implicated in many diseases, as mitochondria have a crucial role in producing energy and metabolites. Finding drugs for mitochondrial diseases is imperative as few mitochondrial diseases have any treatments.
These drugs may either correct mitochondrial function in mitochondrial diseases, or in cancer - which has unusual mitochondrial metabolism - destroy the mitochondria and so kill the cancerous cells too.
The mitochondrion’s crucial role makes it a target for drugs against pathogens. Drugs that prevent mitochondrial function in these organisms will lead to their death. Likewise, bacteria have proteins similar to essential mitochondrial proteins, and knowledge of mitochondrial proteins can be exploited to develop new antibiotics.
For example, Entamoeba histolytica is a parasitic protist infecting 50 million people and causing amoebic dysentry. The current drugs against E. histolytica are becoming ineffective and have side-effects. To find new drugs against E. histolytica, we combine high-throughput and computational screening of commercial libraries in collaboration with Dr. Edmund Kunji and with funding from MRC Technology. To elucidate structure-activity relationships, we built models of the E. histolytica target and docked inhibitors identified in the high-throughput screen.