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School of Medicine
Sinisa Urban of
Molecular Biology and Genetics
on the tricky malaria parasite:
Why has malaria been so overlooked? Is it entirely due to the lack of a U.S. health concern?
URBAN: I think that has a lot to do with it—most people here will never know anyone who has suffered from malaria but will know someone close with cancer or Alzheimer’s. And industry is also not as interested because the people currently affected can’t pay what pharma would have to charge for a cure. They’d get no return, they believe, for taking on this difficult problem.
Focusing on illnesses that affect us is, of course, only natural, but malaria is devastating globally and could even come back to haunt us—it used to occur in this country. Changes in the environment, in public health and therapy eradicated it, but 2003 saw an outbreak here of two or three cases.
Does malaria research hold other benefits besides the obvious medical applications?
URBAN: Yes. One is that evolutionarily, malaria and related parasites are some of the closest relatives to the common eukaryotic ancestor. Essentially, we’re studying eukaryotic cells in their infancy.
Also, these organisms are extremely interesting at a fundamental, cell biology level. They’re obligate parasites, and they have evolved fiendishly clever ways to survive. For example, unlike other pathogens that trick a host cell to take them in through endocytosis, Plasmodia push their way in through an incredible orchestration of events tied to cell motility.
You’ve just settled into a new lab and a new research field. Where do you see your work going?
URBAN: What was most exciting was that the rhomboid enzymes we study don’t act on just one invasion pathway but at the convergence point of several. So we want to understand them at a more proteomic level. If we inhibit them with a drug, for example, does the cell upregulate another arsenal of enzymes to compensate, or are we targeting a genuine Achilles heel?
Also, the malaria parasite has eight rhomboids, but only two or three are involved in invasion; that leaves four or five unaccounted for. Could those enzymes represent an ancient form of cell communication? That’s why we first studied them in fruit flies.