PhD position available to work on nuclear condensate structure

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. Recent work from the supervisors’ labs has uncovered novel molecular principles of paraspeckle assembly and dysregulation in human disease, such as neurodegeneration and viral infections. However, so far, structural studies of paraspeckles have been limited to fluorescent imaging approaches with a ~100 nm resolution limit. Going beyond this limit and dissecting the single molecule-level organisation of paraspeckle complexes should answer important questions of paraspeckle biology and pathology. 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: 1. Establish a pipeline for ultrastructural analysis of paraspeckles using cryo-CLEM. 2. Build a structural (cryo-EM based) model of the canonical paraspeckle condensate. 3. Characterise the ultrastructure of non-canonical paraspeckles such as those formed in virus-infected cells. 4. 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). This project is an excellent opportunity for a flexible and open-minded student to gain scientific knowledge that may become transformative for the field. Proposed start date: 01/10/2026 Entry Requirements: Candidates must have a first or upper second class honours degree or significant research experience. How to apply: Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply Please clearly state the prospective main supervisor in the respective box and select (Neuroscience) as the department.