Wellcome Centre for Integrative Parasitology

The McCulloch Group

Current Research

Current Research: DNA recombination, replication, repair and antigenic variation in trypanosomatid parasites

DNA recombination, replication and repair are central to the functioning and propagation of all organisms, maintaining genome stability for growth and reproduction. Homologous recombination, one of a number of repair pathways in cells, functions in repair of DNA double strand breaks, a severe form of genome damage, and ensures completion of DNA replication. In African trypanosomes, homologous recombination also plays a pivotal role in antigenic variation, a survival strategy that relies on changes in surface antigens (Variant Surface Glycoproteins), allowing host immune response evasion and infection of partially immune hosts. This is a hugely elaborate system, involving expression of a single VSG gene from >1000 silent copies in the genome. We are exploring how homologous recombination and other DNA repair pathways operate in trypanosomes and influence antigenic variation. In addition, we are characterising the process of nuclear DNA replication, which not only appears unusual in this parasite but, remarkably, also influences antigenic variation. Ongoing projects are examining homologous recombination in response to induced DNA double strand breaks, in characterising the machinery and timing of nuclear replication, examining the role of excision repair pathways in mitochondrial and nuclear genome stability, elucidating the DNA damage response in T. brucei, and in the enzymatic machinery and initiation of VSG switching throughout T. brucei chronic infections.

Ross Laidlaw, PhD Student

Felix Warren, PhD Student