Rotation 1: Investigating the role(s) of the putative FANCJ helicase in the malaria parasite Plasmodium falciparum

PfFANCJ is the likely homolog of the Fanconi Anaemia Group J helicase in humans – a helicase with well-characterised roles in DNA repair, genome stability and cancer-prone genetic syndromes in humans. It is hypothesized that it could have roles in G-quadruplex (G4) biology and genome stability in Plasmodium. The Merrick Lab has studied G4 biology in the malaria parasite for over a decade, establishing important roles for G4 motifs in controlling gene recombination, genome stability and gene expression. In model systems, helicases in three different classes can unwind G4 motifs, allowing the passage of DNA and RNA polymerases, and the Merrick Lab has previously characterised far-reaching roles for the RecQ helicases PfBLM and PfWRN. However, PfFANCJ remains unstudied (while the third class, PIF1, appears to be absent in this early-diverging protozoan). PfFANCJ is predicted to be essential, suggesting that it has unique and crucial roles in Plasmodium biology. The lab has previously made an inducible knockdown line for this gene, confirming its essentiality, as well as the expected nuclear location of the protein. This line will be further characterised during the rotation project. If the project continues to PhD, there are many further questions to be answered about this mutant – for example, does it have DNA repair defects; G4 metabolism defects; an intriguing preliminary phenotype that hints at stress-granule formation? What are the genomic and transcriptomic impacts of the knockdown?

Basic Science

Oct 2023 — Sep 2027

United Kingdom