University of Dundee

" Does DNA replication direct the initiating events in host immune evasion by antigenic variation in the African trypanosome? "

Event Date: 
Wednesday, December 14, 2016 - 12:00
Event Location: 
MSI Small Lecture Theatre
Professor Mark Field FRSB
Event Speaker: 
Richard McCulloch
University of Glasgow
Event Type: 

All pathogens must survive host immune attack and, amongst the survival strategies that have evolved, antigenic variation is a particularly widespread reaction to thwart adaptive immunity. Though the reactions that underlie antigenic variation are highly varied, recombination by gene conversion is a widespread approach to immune survival in bacterial and eukaryotic pathogens. In the African trypanosome antigenic variation involves gene conversion-catalysed movement of a huge number of Variant Surface Glycoprotein (VSG) genes into a few telomeric sites for VSG expression, amongst which only a single site is actively transcribed at one time. Genetic evidence indicates VSG gene conversion has co-opted the generalised genome maintenance reaction of homologous recombination, aligning the reaction strategy with targeted rearrangements found in many organisms. What is less clear is how gene conversion might be initiated within the locality of the VSG expression sites. I will discuss work we have contributed to this debate in which we propose that the unique early replication of the single actively transcribed VSG transcription site might establish conditions that lead to localized instability and VSG recombination. In addition, I will present unpublished work that suggests DNA damage signaling and the removal of RNA-associated DNA might be key activities in the initiation of trypanosome antigenic variation.