Unique Biology of Human Parasites Focus of Read Study

The research seeks to expand understanding of gene expression in Trypanosoma brucei, a flagellated protozoan that is a devastating human and veterinary parasite in sub-Saharan Africa and the causative agent of Human African trypanosomiasis (HAT).

HAT is fatal if untreated — vaccination is not an option — and available drugs are toxic, difficult to administer and expensive, according to Read, principal investigator on the study.

“Gene expression in trypanosome parasites is regulated almost exclusively at posttranscriptional levels, which requires RNA-binding proteins (RBPs) as key effectors,” Read says. “Despite their importance in gene expression in trypanosomes, little is known about RBP functions and actions.”

Read’s laboratory previously discovered DRBD18, an RBP that is essential for the survival of the human blood form and the insect vector procyclic form of T. brucei.

Preliminary studies of DRBD18 function suggest that it is involved in nuclear mRNA export and translation initiation and that its functions are regulated by arginine methylation.

“The goal of this study is to define the mechanisms of action of DRBD18 and the role of arginine methylation in regulating its interactions and functions,” Read says.

Specific aims of the study are:

• identifying direct DRBD18 mRNA targets
• mechanistically defining DRBD18 effector pathways
• establishing the methylation responsiveness of DRBD18 interactions and DRBD18 functions

Using combined genetic, genomic and biochemical approaches, the research will provide fundamental insights into specific gene regulatory events in T. brucei and uncover regulatory mechanisms with wide-ranging applicability in trypanosomes, Read says.

“This study will significantly increase our mechanistic understanding of this essential protein in a medically and economically important parasite,” Read says.

The study, titled “Function and Regulation of the Essential RNA Binding Protein, DRBD18,” is funded by the National Institute of Allergy and Infectious Diseases for $2.2 million over five years.

A collaborator on the study from UB is:

• Sarah E. Walker, PhD, assistant professor of biological sciences in the College of Arts and Sciences

Other collaborators are from the following institutions:

• Case Western Reserve University, School of Medicine
• The Center for Infectious Disease Research, University of Washington Department of Global Health