Trypanosoma brucei, the parasite that causes African sleeping sickness, is well known for its infamous disappearing act. Every time the host’s immune system gets close to eliminating the infection, a small number of trypanosomes avoids detection by shedding their surface 'coat' and putting on a new one, distinct from those the immune system already recognizes. The coat covers the entire surface of the parasite and consists of a dense layer of a Variant Surface Glycoprotein (VSG). This process of changing coats is known as antigenic variation.
There are hundreds of VSG genes throughout the trypanosome’s genome, but, at any given time, only one is actively transcribed. During antigenic variation, some parasites switch transcription to a new VSG, causing the surface coats to change their molecular identity. Such transcriptional changes do not involve alterations in the DNA sequence but are inherited nevertheless, which indicates that VSG transcription is under epigenetic control. Our goal is to understand the role chromatin plays in antigenic variation. To that end, we use modern molecular and genetic strategies including RNA interference, chromatin immunoprecipitation, high-throughput deep sequencing and bioinformatics. Understanding how antigenic variation works should allow us to develop drugs that will disrupt VSG regulation, which in turn, would make parasites, at long last, more vulnerable to the host immune defenses.

Post-Doc at The Rockefeller University, New York, USA
Associate researcher at The Rockefeller University, New York, USA
Group Leader at IMM since December 2009

Prof. Brian Chait, The Rockefeller University, New York, USA
Dr. Christian Janzen, University of Munich, Munich, Germany

Prof. Joseph Takahashi, Southwestern University, Dallas, Texas, USA
 

2012 HHMI International Early Career Scientist (Luísa Figueiredo)

Figueiredo LM and Cross GAM (2010) Nucleosomes are depleted at the VSG expression site transcribed by RNA polymerase I in African trypanosomes. Eukaryot Cell; 9(1): 148-154

 

Figueiredo LM, Cross GAM, Janzen CJ. (2009) Epigenetics in African trypanosomes. Nat Rev Microbiol; 7: 504-513

 

Boothroyd CE, Dreesen O, Leonova T, Ly I, Figueiredo LM, Cross GAM, and Papavasiliou FN. (2009) Single endonuclease-generated DNA breaks induce antigenic switching in Trypanosoma brucei Nature; 459: 278-281

 

Yang X, Figueiredo LM, Espinal A, Okubo E and Li B. (2009) RAP1 Is Essential for Silencing Telomeric Variant Surface Glycoprotein Genes in Trypanosoma brucei. Cell; 137: 99-109

 

Figueiredo LM, Janzen CJ, Cross GA. (2008) A Histone Methyltransferase Modulates Antigenic Variation in African Trypanosomes. PLoS Biology; 6 (7): e161

 

Hertz-Fowler C, Figueiredo LM* et al. (2008) Telomeric expression sites are highly conserved in Trypanosoma brucei. PLoS ONE; 3(10) e3527 *shared first authorship

 

Figueiredo LM, Rocha EP, Mancio-Silva L, Prevost C, Hernandez-Verdun D, Scherf A. (2005) The unusually large Plasmodium telomerase reverse-transcriptase localizes in a discrete compartment associated with the nucleolus. Nucleic Acids Res; 33(3):1111-22
 

Drugs for Neglected Diseases initiative
Eukaryotic Pathogen Database Resources
Laboratory of Molecular Parasitology The Rockefeller University