Paraspeckle condensates in cell health, stress and disease – what can structural studies tell us?
About the project
Biomolecular condensates are crucial organisers of cellular biochemistry and hence physiology. The paraspeckle is a stress-responsive nuclear condensate dysregulated in human diseases such as cancer, neurodegeneration and infectious diseases. In contrast to most phase-separated assemblies, paraspeckles are highly ordered, with their size and structure dictated by the properties of the scaffolding RNA molecule. Paraspeckles represent a unique model system for the studies of condensate assembly and function.
Methodology
The internal structure of paraspeckle complexes formed in different cellular contexts will be interrogated by cryogenic Correlative Light and Electron Microscopy (cryo-CLEM). This will be performed utilising cell models with fluorescently labelled paraspeckle complexes, neuronal models with altered paraspeckle states, and models with virally induced paraspeckle-like structures. Structural studies will be performed in the Sheffield cryoEM facility and the Diamond Light Source.
Aims
- Establish a pipeline for ultrastructural analysis of paraspeckles using cryo-CLEM.
- Build a structural (cryo-EM based) model of the canonical paraspeckle condensate.
- Characterise the ultrastructure of non-canonical paraspeckles such as those formed in virus-infected cells.
- Characterise changes to the ultrastructure and stoichiometry of paraspeckle complexes elicited by physiological and pathological conditions.
In addition to cryo-EM, the student will gain experience in mammalian cell culture, RNA biology, advanced imaging and disease modelling (neuronal and viral infection cell models).
Proposed start date: 01/10/2026
Entry Requirements: Candidates must have a first or upper second class honours degree or significant research experience.
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