Goldberg Lab Research


Parasites have evolved many clever ways to infect their hosts and develop within them. Study of these processes at a molecular level should lead to treatment or prevention of parasitic infections that afflict most of humanity. It will also shed light on general principles of biochemistry and cell biology. The organism we are studying is Plasmodium falciparum, a protozoan parasite that causes malaria.


Most of the malaria parasite`s adaptations to intracellular survival are still biological mysteries. Indeed, nearly half of the Plasmodium proteome comprises proteins of unknown function. We are interested in defining the roles of such proteins using a combination of genetic and biochemical approaches.

 

We are particularly interested in proteases and exported proteins. The parasite exports several hundred effector proteins into its host erythrocyte. What are these proteins doing in the host cell and beyond? How do the proteins get out of the parasite? We are excited about several aspartic proteases called plasmepsins, for which we have identified roles in parasite egress and invasion, as well as in protein export.

 

Drug resistance is now a major problem. New drugs are desperately needed. Thousands of antimalarial compounds have been identified in chemical library screens but we don`t know their targets. We are using approaches such as whole genome sequencing of resistant mutants, allelic replacement and chemical genetics to define promising new drug targets.

 

Our work involves a combination of biochemical, genetic, genomic, cell biological, and physiological approaches aimed at understanding the biology of this nefarious organism.