Deciphering G-Quadruplex function in transposon DNA nuclear import and transposition

Transposons are mobile DNA sequences capable of moving to new genomic locations and can dynamically shape genome evolution. However, the mechanisms that govern their successful integration into host genomes remain poorly understood. The Arabidopsis transposon COPIA
93 is a compelling model due to its exceptionally high transposition activity. During its replication cycle, COPIA
93 forms extrachromosomal DNA with a single-stranded "flap" at its central polypurine tract (cPPT), a structural feature known to mediate nuclear entry in retroviruses.

Recently, we discovered that this guanine-rich cPPT region folds into a non-canonical G-quadruplex structure. Unlike the classic double helix, a G-quadruplex is a stable, four-stranded nucleic acid architecture formed when four guanine bases group into stacked and planar arrangements. These structures often act as molecular switches by influencing DNA stability and protein binding.

This DPhil project aims to investigate whether the COPIA
93 G-quadruplex acts as a dynamic structural switch that recruits host factors to facilitate nuclear entry and boost transposition efficiency. By combining molecular biology, structural genetics, and bioinformatic approaches, this project offers an exciting opportunity to bridge plant transposable element biology with retro virology. Ultimately, this research will uncover how non-canonical DNA structures regulate genome mobility and reveal conserved evolutionary strategies shared across kingdoms.

This DPhil project aims to determine the structural and functional roles of the G-quadruplex and its associated DNA flap in COPIA
93 retro transposition. The student will test the hypothesis that G-quadruplex folding within the cPPT-like region is essential for nuclear import and subsequent genomic integration events in plants. To address this, the project encompasses four integrated objectives: mapping and validating the G-quadruplex architecture in vitro and in vivo using circular dichroism, chemical probing, and high-throughput sequencing; investigating how structure-disrupting mutations impact pre-integration complex assembly, nuclear import efficiency, and cellular localisation via fluorescence microscopy;

evaluating downstream consequences on transposition rates; and identifying host proteins or nuclear import receptors that interact with the DNA flap and non-canonical DNA architecture.

By achieving these goals, the student will uncover novel molecular mechanisms driving plant retrotransposon mobility, advance our fundamental understanding of atypical DNA conformations in plant genome dynamics, and potentially reveal regulatory targets to control transposon activity or improve genetic delivery tools in plant biotechnology.

Day-to-day research will combine molecular biology, biochemistry, plant genetics, and computational biology. Key techniques include nucleic acid extraction, biophysical assays such as circular dichroism to probe G-quadruplex folding, molecular cloning, and plant transformation assays to analyse nuclear import and transposition frequencies in planta. Quantitative PCR, digital PCR, and high-throughput sequencing will track sub-cellular localisation and extrachromosomal DNA dynamics. Beyond wet-lab experimentation, students will gain valuable, highly transferable skills, including complex bioinformatic data analysis, rigorous experimental design, statistical modeling, project management, and scientific communication through report writing and data presentation.

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This project is part of the DPhil in Biology programme, and is not a funded course at the University of Oxford; as such, students are expected to explore options for funding. However, we anticipate being able to offer around 6 full graduate scholarships to incoming DPhil students in 2027/28.

You will be automatically considered for several Oxford scholarships, which cover fees and stipend, if you fulfil the eligibility criteria and submit your graduate application by 6 January 2026. Scholarships are awarded based on academic achievement and potential to excel as a DPhil student.

For further details about searching for funding as a graduate student visit the graduate study information on our website.

For full entry requirements and eligibility information, please see the main admissions page.