Approved Research

Investigation of the relationship between polymorphisms in genes related to type I interferon signalling and human inflammatory disease states

Lay summary

Viruses are tiny organisms that are everywhere. In order to make more copies of themselves viruses infect the cells of other organisms, including humans. Being able to fight off viruses is absolutely necessary for our survival; simply put, if a person cannot do so, they will die.

How do our cells realise that they are being infected by a virus? It turns out that we do this by sensing the presence of viral genetic material (called DNA and RNA) as the virus enters the cell. Much as a dog might bark to wake up the owner when a burglar breaks into a house, our cells 'raise the alarm' when they sense viral DNA and RNA by producing a very powerful chemical called interferon. Interferon acts as a kind of cellular disinfectant and is very good at killing virus. However, like a disinfectant, too much interferon can be dangerous, so that it is important that interferon is used carefully, and only when needed.

Over the last 20 years, we have learned that certain human diseases are associated with high levels of interferon. As explained above, we know that interferon is normally only produced when we are infected with a virus. The question arises then, why are levels of interferon abnormally high in these conditions? The answer to this question is explained by the fact that our own cells are full of our own DNA and RNA, which also has the potential to trigger the production of interferon. Because of this, safety mechanisms exist to minimise the risk that we might 'misinterpret' our own DNA and RNA as virus. In general terms, the faster and more efficient a person is at producing interferon, and killing virus, the better. However, we think that as humans have lived longer, the risk of inflammatory disease due to higher levels of interferon has increased.

In our study, we intend to explore a possible link between variations in the genetic code of members of the general population (concentrating on chemicals that are important in interferon signalling), and diseases where a link to interferon has already been described. The latter include common disoders such as systemic lupus erythematosus, psoriasis, diabetes mellitus and rheumatoid arthritis. We will then explore any possible genetic variations to experiments that we can undertake in the laboratory. This work will not involve re-contacting Biobank participants, or using samples deposited in the Biobank.