Parasite-caused diseases such as malaria kill millions of people each year, and eradication efforts have been largely futile. But developing a clear understanding of how to exploit emerging information from genome research is the first step in developing effective, safe and affordable drugs that can combat many such diseases, said Pradipsinh Rathod, a 91探花chemistry professor. For instance, understanding how a single protein called DHFR is regulated in mammals and how it functions differently in the malaria-causing parasite Plasmodium eventually could mean a breakthrough in identifying other good targets for attacking Plasmodium and ultimately killing the deadly pathogen, Rathod said. Rathod and former graduate student Kai Zhang, now a post-doctoral researcher at the Washington University School of Medicine in St. Louis, are co-authors of a paper detailing the work in the April 19 edition of the journal Science. The work supports a shift in how scientists think about treating infectious diseases, improving on many of the increasingly ineffective remedies that are currently used, Rathod said. 鈥淲e are reinterpreting what has worked well previously, not just through a half-century-old standard for selective drug action but in the context of our most current understanding of how the cell works,鈥� he said. 鈥淏y combining that reinterpretation with new tools developed in the last few years, we鈥檙e discovering that there鈥檚 a lot more to finding drugs that work well.鈥� Much is being learned from the study of the human genome, and work on the malaria genome is expected to be finished this year, allowing for the first time a direct search for metabolic differences between host and parasite on an unprecedented scale, Rathod said. That in turn will inspire hunts for pharmaceuticals that will selectively kill parasites while doing minimum damage to the host cell. 鈥淏ut such efforts will be futile if our models for selective drug action are incomplete,鈥� he said. In the current research, Zhang and Rathod found that parasites are sensitive to drugs that target their DHFR in part because of their inability to rapidly replenish the dead enzyme. Host cells, on the other hand, can rapidly generate excess amounts of the DHFR protein if the drug accidentally enters the host cell. Previously, it was believed the different effects between parasite and host were entirely related to how tightly the drug used against the parasite was bound to the DHFR protein in the parasite. The latest research offers a new standard for selective targeting, Rathod said. He likens it to the military establishing a battle plan based on good intelligence. 鈥淵ou can have all the maps, you can have all the guns, you can have all the firepower, but if you don鈥檛 know where the important targets are, it鈥檚 a waste. You can do as much harm as good,鈥� he said. The Science paper focuses on malaria, a disease that each year strikes one-seventh of the world鈥檚 population 鈥� 900 million people, mostly in southern Asia, sub-Saharan Africa and Central and South America 鈥� and kills 2.7 million people. However, the same concepts could apply to research into, for example, HIV, cancer, heart disease or Alzheimer鈥檚 disease, Rathod said. The goal is finding the means to attack certain kinds of cells in ways that aren鈥檛 toxic to other cells, even cells similar to the ones being attacked. Malaria is the focus of research in Rathod鈥檚 lab because it is so widespread and often affects some of the world鈥檚 poorest populations. In some parts of Africa, for example, many people infected with malaria would be hard pressed to pay even $10 a year for medication, Rathod said. Solving a problem of that magnitude will require scientists, drug manufacturers and social agencies to work together, he said. 鈥淢alaria is a big issue because no vaccines have worked,鈥� he said. 鈥淢edications have worked in the past but new ones have to be cheap and they have to be nontoxic. Currently there鈥檚 not a lot of incentive for drug companies because they think there鈥檚 no way that they鈥檙e ever going to recover their investment. We must make the drug-development process more rational and more efficient.鈥�