Mr Januka Athukoralage

Postgraduate Student/Demonstrator

BSRC 
tel.
fax.
jsa8@st-andrews.ac.uk

I study virus-host conflict in prokaryotes, primarily focusing on the model hyperthermophilic archaeon Sulfolobus solfataricus. Nearly all prokaryotes defend against viruses using an adaptive immune system known as CRISPR-Cas. CRISPR-Cas detects and cuts the genetic material of the virus. We study the type III CRISPR-Cas system which (among other enzymatic activities) also synthesise cyclic oligoadenylate second messengers in response to virus detection. Cyclic oligoadenylates awaken defence enzymes, which protect against invading genetic elements by degrading RNA in the cell. Uncontrolled RNA cleavage in the cell can be dangerous and potentially catastrophic, and therefore off-switches are required to deactivate defence enzymes activated by the CRISPR response.

My work focuses on mechanistic studies on cyclic oligoadenylate signaling and the discovery and characterisation of defence off-switches. Termed CRISPR ring nuclease, cellular off-switches degrade cyclic oligoadenylates to deactivate defence enzymes and limit collateral damage to the host.

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. The anti-CRISPR ring nuclease degrades cyclic oligoadenylates much faster than the cellular counterpart, preventing defence enzymes from being activated. This gives some viruses the upper hand, allowing them to propagate unhindered.

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)

 

Publications

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

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