Analysis of CIZ1 function in development and disease

FUNDING: 10 weeks (full time, 37 hrs per week, £12 per hour, £1000 consumables)
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Elena Guglielmi, Biology, York

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The nuclear matrix protein CIZ1 associates with cyclins to promote DNA replication and is involved in stabilisation of heterochromatin, notably at the inactive X chromosome in females. Late-onset female-specific lymphoproliferative disorders with highly enlarged lymphoid tissues (spleens) as well as gender-unbiased leukaemia have been reported in CIZ1-null mice, highlighting CIZ1 as a potential tumour suppressor. Recent analysis has revealed an imbalance in haematopoietic stem cells (HSCs) and excessive DNA damage checkpoint activation in CIZ1-null mice at 8-10 weeks. This suggests a potential early quiescence-linked defect in the haematopoietic system as early as 3 weeks postpartum, when HSCs move from being actively cycling to a reserve pool of quiescent HSCs (foetal-to-adult switch). The successful student will be working with banked mouse spleens from wild type and CIZ1-null mice at 8-10 weeks to conduct analyses on the composition and morphology of normal/pre-diseased spleens. Students will receive training to perform cryosectioning and immunostaining, cell cycle assays, immunofluorescence microscopy, and image analysis. Students will be expected to present their findings orally at a research day in York in September 2024.