CRISPR-Cas systems offer precise DNA sequence recognition but largely ignore epigenetic features such as methylation, limiting their ability to distinguish identical sequences in different regulatory states. This PhD project aims to engineer CRISPR-Cas enzymes whose activity depends on epigenetic marks, introducing an orthogonal, context-aware axis of target recognition beyond nucleotide sequence.
The project integrates experimental enzyme evolution and computational protein design. Experimentally, we will construct large libraries of Cas variants to screen for activity in response to epigenetic markers via iterative rounds of selection, enrichment, and molecular characterization. We will use cutting edge machine learning tools to prioritize variants across evolution cycles and structure-aware approaches to design structurally plausible protein-DNA interactions for high-throughput screening. These strategies will enable systematic exploration of otherwise intractable protein sequence space. By overcoming current limitations in epigenetic discrimination, this project could enable new therapeutic strategies for diseases where epigenetic dysregulation is central.
The project is suitable for ambitious students with demonstrated wet lab skills and solid computational experience, including proven experience with the Python programming language. The student should be very motivated to operate at the interface of genome editing and machine learning. The student must have a Masters degree before entering the PhD program at Vilnius University. This position will be funded by either a scholarship from Lithuania or by existing funding in the Jones!Lab.
Applicants must email a CV and motivation letter to Dr. Jonas Kubilius (Senior researcher in the Jones Lab) with the subject line beginning: [PhD2026].
Tagged as: Life Sciences
Please visit euraxess.ec.europa.eu.
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