Mr Januka Athukoralage

Postgraduate Student/Demonstrator


My research is focused on virus-host conflict in bacteria and archaeaAlmost all prokaryotes use an adaptive immune system known as CRISPR-Cas to defend against infection by viruses and phage. Guided by genetic memories of past infection, CRISPR-Cas systems detect and degrade foreign genetic material. We study the type III CRISPR-Cas system which also synthesises cyclic oligoadenylate second messengers in response to infection. Cyclic oligoadenylates stimulate additional defences in cells. Among these, cyclic oligoadenylate activated defence nucleases protect the cell by degrading RNA non-specifically, which slows down viral replication at the cost of cell growth. Uncontrolled RNA cleavage can be dangerous and potentially catastrophic, therefore off-switches are required to degrade the cyclic oligoadenylate alarm signal and deactivate defence enzymes if cells are to recover. 

My work centres on mechanistic studies on cyclic oligoadenylate signalling and the discovery and characterisation of defence off-switches. Termed CRISPR ring nuclease, the cellular off-switches we have identified degrade cyclic oligoadenylates and deactivate defence enzymes to regulate the potency of the immune response. 

In their battle for survival, viruses encode proteins to block CRISPR-Cas systems. These are known as Anti-CRISPRs. Remarkably, viruses have evolved their own anti-CRISPR ring nuclease variants. The anti-CRISPR ring nuclease degrades cyclic oligoadenylates much faster than the cellular counterpart and stops defence enzymes being activated. This gives viruses the upper hand; allowing them to propagate despite being detected by the cell.

The billion year war between prokaryotes and their viruses continue, and our study of their arsenals, used in offence and for defence, continue to uncover new tools that can be repurposed for biotechnology and medicine.  

(source: symbiosis database)



Mr Januka Athukoralage
Biomedical Sciences Building
University of St Andrews
North Haugh
St Andrews
KY16 9ST

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