The VEXing problem of single gene choice in African trypanosomes

Event details

Speaker: Dr Joana Faria

Trypanosoma brucei is a parasitic protozoan and the causative agent of African sleeping sickness; it undergoes antigenic variation, successfully avoiding the host immune response by switching its variant surface glycoprotein (VSG). Indeed, antigenic variation is a powerful immune evasion strategy employed by several other pathogens such as malaria and Giardia parasites. VSGs are expressed in a monoallelic fashion from thousands of possible genes, rendering them one of the most impressive examples of single gene choice, similarly to olfactory and antigen receptors in mammals. However, despite intense study, the mechanisms governing single gene-choice have remained mysterious for decades, one of the greatest enigmas of eukaryotic gene expression.

During Dr Faria's postdoctoral work, she has applied various orthogonal techniques and she has identified the protein complex that regulates VSG-singular expression, the first allelic exclusion complex in any eukaryote. Moreover, Dr Faria has discovered that the active-VSG locus resides within a membraneless sub-nuclear organelle where Pol-I and Pol-II transcription coincide. This organelle functions as a transcription and splicing factory that sustains the high VSG expression rate. These findings shed light on the epigenetic processes underpinning how cells express just one gene from a large family and how sub-nuclear compartments can be arranged to enhance expression of specific genes.

Please note room change.