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Evolutionary principles of nuclear dynamics and remodelling

Periodic Reporting for period 1 - KaryodynEVO (Evolutionary principles of nuclear dynamics and remodelling)

Periodo di rendicontazione: 2023-04-01 al 2025-09-30

All eukaryotes have a nucleus that insulates the genetic material from the cytoplasm, but despite the fundamental and universal nature of this cellular compartment, species have evolved a bewildering diversity of strategies to reorganise and partition the nucleus through the cell cycle. Using a multifaceted interdisciplinary approach that includes comparative genomics, quantitative cell biology in multiple microbial model systems, and experimental evolution, we set out in this project to understand the fundamental principles underlying the evolution of nuclear remodelling and dynamics. We expect this work to have implications beyond fundamental principles of cell biology, providing a general template for evolution-guided cell biology investigations and shaping the way we understand nuclear function in health and disease.
At this halfway stage of the project, we have made major strides in the comparative genomics (WP1) and comparative phenomics across eukaryotic groups (WP2), in fact far exceeding our initial expectations thanks to the unanticipated success of expansion microscopy (ExM) in producing atlas-scale cytoskeletal phenotyping. Additionally, we have achieved several milestones in using yeast models to understand evolutionary repair of nuclear processes (WP3 and WP4) and developed a significant protocol base for the understudied model for developmental karyodynamic rewiring, the slime mould Physarum polycephalum. For this module (WP5) and for the evolutionary reconstruction module (WP6), we are producing our first exciting preliminary results.
The work has already resulted in 5 high-impact and well-received peer-reviewed publications with several more preprinted and in the pipeline, and has been presented at multiple international conferences across Europe and the world, including recently in Korea and India. Our technical work on expansion microscopy (WP2) and image-guided experimental evolution (WP4) opens up several avenues for broader exploitation, either through teaching and dissemination of the technique (ExM) or through exploring the potential for commercialisation (image-guided evolution). We will use the latter as the basis for an ERC PoC application later this year or next year.
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