David
M. Engman, MD, PhD
Associate Professor
Departments of Pathology and Microbiology-Immunology
To Contact Dr. Engman:
phone: 312-503-1288
e-mail: d-engman@northwestern.edu
Dr. Engman's website
Research Interests
Research in the Engman
laboratory focuses on the molecular biology of trypanosomes, with particular
emphasis on organelle biogenesis and the pathogenesis of trypanosomal diseases.
Trypanosomes are single-celled eukaryotic parasites that cause diseases such as African sleeping sickness and Chagas disease. They have complex life cycles involving insect and mammalian hosts and display a number of unique features that make them powerful model organisms for the study of genetics and molecular biology. The trypanosome genomes are approximately 50,000,000 bp in size and are organized in dozens to hundreds of linear chromosomes. Nuclear gene expression in trypanosomes is unusual. With few exceptions, there are no promotors and gene transcription does not occur with discrete start and stop points. Rather, an entire chromosome is transcribed in both directions from a single chromosome-internal initiation point, and individual mRNAs are generated via polyadenylation and the addition of a 39-nt spliced leader sequence to the 5' end of each coding region. Mitochondrial gene expression is equally remarkable. A number of mitochondrial genes are unidentifiable by DNA sequence, although the corresponding mRNAs are normal and are translated into proteins participating in a number of important mitochondrial processes. The "nonsense" genes are transcribed into pre-mRNAs whose sequences are "corrected" via the process of RNA editing: small antisense RNAs serve as templates for the addition or deletion of uridine residues to the transcripts, which ultimately results in mRNAs having intact coding sequences.