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Hidden Guardians: How Chromatin Structure Shapes the Body’s First Line of Defence at University of Birmingham

University of Birmingham
Full-time
On-site
GB

Every cell contains two metres of DNA, all packed into the nucleus. DNA is wrapped around proteins to form chromatin, which can be tightly compacted (closed) or loosely packed (open), depending on whether the cell needs to read that part of the genome.

Recent evidence suggests that this packaging doesn’t just organise DNA — it may also influence how cells defend themselves.

Cells rely on their innate immune system as a first line of defence against viruses and other invaders. A central part of this defence is the ability to detect “misplaced” DNA — for example, viral DNA in the cytoplasm. Detection triggers production of interferons, alarm signals that switch on hundreds of protective genes. To prevent false alarms, cells use nucleases to chop up stray DNA.

This project asks:

How does the way DNA is packaged (chromatin compaction) influence how strongly cells mount an interferon response?

To investigate this, you’ll use:

• ATAC-seq & RNA-seq: to measure which parts of the genome are open/closed, and which genes are switched on.

• Recombinant DNA tools: to engineer the DNA sensor and identify which DNA fragments interact with it.

• Fluorescent microscopy: to track DNA and chromatin changes in living cells, and check nuclear integrity.

• Western blotting & depletion assays: to analyse activation of the cGAS–STING pathway, the central DNA-sensing mechanism.

By the end, you’ll gain hands-on experience in molecular biology, imaging, and bioinformatics, and help answer a fundamental question at the crossroads of genome biology and immunology: does nuclear organisation itself set the stage for how cells fight infection?

Supervisors:

Professor Jo Morris (University of Birmingham) and Dr Alexiane Decout (University of Warwick)

Funding notes:

This is a PhD studentship with the Midlands Integrated Biosciences Training Partnership, funded by BBSRC and in partnership with the University of Warwick, Aston University, Harper Adams University, Coventry University, and the University of Leicester.

For more details please visit: https://warwick.ac.uk/fac/cross_fac/mibtp/ or https://www.birmingham.ac.uk/about/college-of-life-and-environmental-sciences/midlands-integrative-biosciences-training-partnership

How to apply:

To apply, please follow this link, make an account, and submit an application via the university online admissions portal: https://sits.bham.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=FR167D&code2=0005. This link is unique to the MIBTP programme; please do not use any other link to apply to this project or your application may be rejected.