Williams Using Grant to Study Disease-Causing Parasite Structure

The grant, from the National Institute of General Medical Sciences, will allow Williams and her team to work on developing an assay to identify drugs to target the parasite.

Ribosomes are the molecular machines that function to make proteins. They are comprised of both ribosomal RNAs (rRNAs), which perform the catalytic function of protein synthesis, and a large number of proteins that form the structural scaffold of the ribosome.

“Our laboratory has shown that there are critically important differences in the process of ribosome formation in the parasitic organism we study, Trypanosoma brucei, the organism that causes African sleeping sickness,” Williams says.

Williams says the research will first focus on learning more about the small complex that brings 5S rRNA to the forming ribosome and then to identify the critical interactions in the complex that are required for the parasite to survive.

Lastly, the researchers’ goal is to identify compounds that target those interactions through drug screening.

Williams said her laboratory has defined the earliest preribosomal particle in trypanosomes, which contains the conserved components 5S rRNA and L5 as well as the trypanosome-specific proteins, P34/P37.

She says her team’s research has shown that both L5 and P34/P37 are essential to the formation of functional ribosomes and therefore, the viability of T. brucei.

Although the ribosome is highly conserved, subtle differences between the host and pathogen have enabled the development of drugs specifically targeting pathogen ribosome assembly and function, Williams says.

“Our hypothesis is that the interactions between the components of the essential preribosomal complex will provide valid targets for chemotherapeutic disruption of ribosomal assembly in T. brucei,” she says.

“Our goals are to exploit the differences that will allow us to specifically target the parasite and not the human host.”

With the grant, Williams, who is the principal investigator, has three goals:

• first, to determine the critical proteins that enable the association of the 5S rRNA-containing complex with the ribosome and their function in ribosome biogenesis
• second, to define the interaction network among the preribosomal complex components and examine how disruption affects the function of the complex within the cell
• third, to develop Förster resonance energy transfer approaches to study in vivo protein-protein interactions and screen for small interfering molecules

“Our work will also continue to provide new insights that will impact the broader field of eukaryotic ribosomal biogenesis,” Williams says.