Importance of Research:
There is only a handful of disproportionately impactful instances of endogenous genome editing scattered across the tree of life – a new one hasn’t been discovered in 20 years. This PhD therefore represents an extremely rare opportunity to explore a novel phenomenon of tremendous impact: plant-parasitic nematodes threaten global food security.
Project Summary:
We recently discovered a novel form of somatic genome editing in the HYPer-variable effectors of plant-parasitic nematodes (Sonawala et al., 2024, Cell Genomics). The data support a mechanism of programmed genetic variation, where alterations are locus specific, strictly governed by rules, and theoretically produce thousands of variants without errors or scars. This project will explore how and why plant-parasitic nematodes edit HYP genes using state-of-the-art techniques.
HYP editing is of great interest because: i) plant-parasitic nematodes inflict combined damages of $100 billion USD annually on agriculture, so understanding the mechanics of nematode parasitism is in a wider context of crop health; ii) Endogenous genome editing is exceedingly rare and impactful, so it is of broad fundamental importance to investigate; and iii) the system that performs the editing can potentially be harnessed in revolutionary molecular biology applications, as shown by the TALENS and CRISPR-Cas9 genome editing systems developed from analogous natural mechanisms in bacteria.
What will the successful applicant do?
The exact nature of the experiments will of course be tailored to the experience and/or interests of the successful applicant. However, experiments can include the latest generation of DNA sequencing methods, high throughput screening, advanced protein modeling, and protein-protein interactions.
References:
Sonawala, Unnati, et al. "A gene with a thousand alleles: The hyper-variable effectors of plant-parasitic nematodes." Cell Genomics (2024). DOI:10.1016/j.xgen.2024.100580
Hanlon et al., “When and how organisms edit their own genomes” Nature Genetics (2025) – in press.