It’s been a busy time over at team OpenBio. Since our last update we have all finished our undergraduate degrees, found ourselves in the intervening summer and started new ventures in the form of PhDs. We thought it was about time then that we sat down and wrote a quick note to explain what we’re doing and why we’re doing it. I’ll get us going…
The next 4 years of my life – ‘Inflammasomes in disease’
I’m currently working at the University of Manchester on a PhD based on the immune system and inflammation in disease. Our immune system is comprised of a special set of cells which act by recognising things like bacteria or parasites and trying to prevent them damaging us. They do this either by releasing chemicals designed to break up the pathogen (a name for something that generates pathology or disease) or just by eating it up and spitting out the harmless debris (a process called ‘phagocytosis’ from the greek ‘phagein’ – to devour).
But how do our immune cells know what is a pathogen and what is just part of our own bodies? We have two different subsets of immune system called the ‘adaptive’ and ‘innate’, each using a slightly different mechanism to detect infection. The adaptive immune system involves a very complicated system in which cells recognise particles they haven’t seen before then produce antibodies against them. The only issue with is that this takes time and the infection may be rapidly damaging our bodies beyond repair. That’s where the innate system comes in, it is able not only to recognise sequences on pathogens but also cleverly can be activated by signals released when our own cells die. This way we can initiate a swift immune response as soon as damage is done even if the pathogen is one our cells have never seen before.
Despite this rapid action, recognition of infection by the innate immune system does have its drawbacks. If our cells die without any infection (for example in stroke) the immune cells are still activated and still release harmful chemicals, this is a phenomenon known as ‘sterile inflammation’. Until fairly recently we thought our immune system was only important in fighting infection by things like bacteria and parasites. More recent research, however, has shown that overactive immune cells may be largely responsible for the damaging effects of a huge number of diseases including stroke, cardiovascular disease, diabetes, Alzheimer’s disease and cancer along with many others.
One of the primary mediators in sterile inflammation is a cytokine called interleukin-1 beta (or IL-1β for short). IL-1β acts as the initiator of a huge number of immune cell processes and is hugely overactive in the diseases listed in the previous paragraph, this makes it really important to understand how it works. Interestingly, the cytokine is released in a mechanism distinct from any other protein, one which we currently do not fully understand. What we do know, however, is that it is governed by a large bundle of proteins called an ‘inflammasome’.
My PhD is based around discovering how inflammasomes work and precisely how they are involved in diseases such as Alzheimer’s and stroke. With this knowledge we will hopefully understand more about the diseases and may even be able to design drugs to inhibit inflammasomes and alleviate the damage caused by IL-1β in disease.