Popular Science Presentation

Disease-causing microorganisms place a huge burden on the people of the world. One example is Plasmodium falciparum, the parasite that causes malaria. The World Health Organization (WHO) estimates that a million people, mostly small children in Africa, die of malaria each year, and that half of the world’s population lives in areas where the risk of contracting the disease is high. Another striking example is Mycobacterium tuberculosis, which is thought to infect one-third of world’s population, albeit in an inactive form. When activated, these bacteria cause tuberculosis, which kills approximately 1.4 million people every year. These two diseases are important causes of poverty and suffering in the third world, and the increasing resistance of the relevant pathogens to the available drugs worsens the situation considerably. New drugs are urgently needed, yet there is little incentive for pharmaceutical companies to invest in developing drugs from which they can expect little or no profit. It is therefore important for academic laboratories to take on some of the burden; projects carried out in collaboration with industrial partners seem to offer the best way forward.

More interesting for big pharma, and a more tangible threat for those living in industrialized countries, are the so-called ESKAPE pathogens. These antibiotic-resistant bacteria cause the majority of infections acquired by patients in conjunction with hospital care. Such infections are particularly sinister, since admission to a hospital is intended to cure the patient, not give them an even worse illness than they had upon arrival!

In our lab, we focus on enzymes (catalytic proteins) that pathogens require, but which are not found in humans. We clone, express and purify sufficient quantities of the chosen proteins, and study how they look using a method called X-ray crystallography. In parallel, we try to identify small molecules (inhibitors) that block the function of the pathogen’s enzymes, without harmful effects on the human host. We also design completely new inhibitor molecules, using our knowledge about how the enzymes look, and seek others using high-throughput screening.