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New enzymes as novel anti-inflammatory therapies.

Signalling peptides play a pivotal role in the body’s immune defence against infection and invasion. This normally results in the removal of any invading bacteria and not surprisingly is well-regulated. However, under certain circumstances the control fails which leads to complications, some of which involve chronic inflammation (e.g. rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease). Bacteria produce an array of enzymes, predominantly proteases, which can interfere with the host’s ability to respond to the presence of the bacteria. Not all bacteria are unwelcome and some are essential for the well-being of the host. These are termed the commensal bacteria, or microbiota. Commensal bacteria have to live in a ‘hostile’ environment, one that is primed to remove unwanted bacteria. They have to interact with the host defence system in order to persist, they do this by dampening down the host response and by neutralizing some of the host factors involved in the removal system.
One of the most complex interactions between commensals and the host is in the gut. In collaboration with Prof O’Toole at the APC in UCC, we will use computer based tools to mine genomic data from human gut microbiota and profile their gene content. Target genes will be identified in this process and then cloned into an Escherichia coli expression system for production of recombinant protein. This protein will enable determination of enzyme activity and allow evaluation of the enzyme as a potential candidate for therapy development for new approaches to the treatment of inflammatory diseases.