A systems biology approach to reveal how the ubiquitin system contributes to asthmatic inflammation
In people with asthma, the immune system is overactive in the lungs and airways, causing inflammation in response to triggers that would not normally be recognised as ‘dangerous’. Current drugs to treat this inflammation, while effective in most people with asthma, can result in side effects and tackle the inflammation in a general way. In order to develop drugs that work better for people with asthma, and work for all people with asthma, we need to better understand the specific processes going on in the airway inflammation so that we can develop specific ways to stop these from occurring.
There is a particular system in the body that is responsible for which and when proteins in each cell are destroyed after they have done their job. This is essential for the healthy functioning of cells and their reaction to their environment. Whenever this switch-off mechanism fails to work properly an inflammatory response is seen, similar to the overactive inflammation observed in asthma.However, it’s thought that this process is what underlies the overactive inflammation in asthma. This system uses a variety of different 'markers' to identify the proteins that are to be destroyed, in a pattern and process that we don’t fully understand. Identifying the specific markers and patterns involved in the airways could provide the key to shutting off the harmful inflammation that occurs during asthma, and with reduced side effects than current drugs.
Dr Maluquer de Motes' research team have already identified some of these specific markers. The research team will continue to identify the specific markers that are involved in airway inflammation. They will also investigate which markers are involved in causing inflammation in people without asthma, and which are specific to reaction to known causes of asthma attacks such as infection by a virus (like a cold), so identifying the markers that are unique to asthma.
Current asthma treatments do not work for everyone, may have side effects (especially when people need to take high doses of oral steroids for long periods), and are very general in their targeting of inflammation. By better understanding the specific proteins and chemical signals in airway cells that can lead to inflammation, the researchers can put us on the path to developing much more specific drug treatments for people with asthma, with fewer side effects and that will hopefully benefit many more people with the condition.
I am Reader and Principal Investigator at the University of Surrey, United Kingdom. I obtained my PhD in Virology in the University of Barcelona. I then joined the laboratory of Claude Krummenacher and Gary Cohen at the University of Pennsylvania to study herpesvirus immune evasion. In 2009 I joined the laboratory of Geoffrey Smith at Imperial College London and subsequently the University of Cambridge to study vaccinia virus modulation of innate immunity and cell death. In 2014 I established my independent research group in the University of Surrey where I am leading a team funded by the main British research councils as well as small charities to investigate virus host-interactions and immune regulation.