Cause

< Back to Research Projects

Projects

MRC-Asthma UK Centre in Allergic Mechanisms of Asthma

The MRC-Asthma UK Centre in Allergic Mechanisms of Asthma is one of our flagship research centres, supporting cutting-edge, world-leading research. Asthma UK has supported the Centre since 2011. The Centre is a collaboration between King's College London and Imperial College London.

 

Investigating a potential reason why asthma is more severe in some people

  • Researcher: Dr Tara Sutherland is a researcher at the University of Edinburgh
  • Start date: January 2016
  • How long will the project run for? 36 months
  • Project type: Project grant (funded in collaboration with the Medical Research Foundation (MRF))
  • Cost: £289,232 (Asthma UK's contribution is £86,770 – this was funded in collaboration with the MRF)

Project title: Chitinase-like proteins: the missing link in allergen-induced neutrophilic inflammation.

Inflammation is a core underlying cause of asthma. People with asthma have inflammation in their lungs, which can be made worse by triggers such as allergens or pollution. For most people with asthma, preventer inhalers can be used to reduce the inflammation in the lungs.

People with severe, poorly controlled asthma often have a different type of inflammation compared to people with milder forms of the disease – but what processes lead to this is unclear. Current treatments do not work very well in people with severe asthma, possibly as a result of this different kind of inflammation; understanding the behaviour of cells involved in this type of inflammation could help to identify targets for treatments for people with severe asthma.

There are types of proteins called CLPs (chitinase-like proteins) that are made by cells found in the lungs of people with asthma, and are produced at higher levels in people with more severe asthma. CLPs cause inflammation and greater amounts of them in people with more severe asthma may explain the greater inflammation present in their lungs.

CLPs have also been shown to be a cause of the different type of inflammation seen in people with severe asthma, by sending signals that tell these immune cells to move into the lungs.

We know that 'asthma' is not just one condition, but that there are many different types of asthma with many different things happening inside the lungs. This research will take us a step closer to understanding what is happening in the lungs of people with severe asthma, and move us closer to developing a treatment to stop the inflammation that causes their disease.

Current treatments don't work very well for people with severe asthma, so a better understanding of the differences occurring in their lungs and moving towards better treatments is essential.

 

Looking for small genetic differences as a cause of asthma

  • Researcher: Dr Rachel Clifford is a researcher at the University of Nottingham
  • Start date: March 2016
  • How long will the project run for? 36 months
  • Project type: Project grant (funded in collaboration with the Medical Research Foundation (MRF)).
  • Cost: £299,645 (Asthma UK's contribution is £89,894 – this was funded in collaboration with the MRF)

Project title: Airway smooth muscle (ASM) DNA methylation: A novel target for asthma therapy

All of our cells contain all of our DNA – this is a lot of information, and each cell will only need to use a tiny amount of it to do its job well. The body has a very clever system to 'wrap up' the DNA that isn't needed so that it fits into a small space, and for highlighting the genes that should be used by a cell. This means that a cell in the muscles in our airway only 'sees' information that will help it to be an airway muscle cell and irrelevant information about its job, for example information about the colour of our eyes, is locked out of the way.

However, sometimes there are genes within a cell that are needed sometimes and not others – these will be 'visible' to a cell, and a separate clever signalling process is used to show which genes should be 'on' and which should be 'off' at any time.

Sometimes, this signalling process goes awry and gives the cells the wrong signal – this can result in cells that misbehave. In the case of asthma, it's thought that airway muscle cells in people with asthma have this confusion, which results in them becoming more 'twitchy' and contracting too often, causing asthma symptoms.

We think that things that act as triggers for some people’s asthma symptoms – such as allergies, or smoking - play a role in this faulty signalling, which may be why they cause asthma symptoms.

Dr Clifford has previously worked on techniques to better understand this signalling system and how to use that information to understand problems in cells.

Researchers have identified several genes that are particularly interesting in airway muscle cells – Dr Clifford will now examine these to see if the signalling for which genes should be 'on' or 'off' is different in people with asthma than those without the condition.

There is the potential to create drugs that target this signalling process, and may be able to correct it if it's different in the airway muscle cells of people with asthma. Knowing what these differences are, and what genes the signals are different for, is a crucial first step towards this.

Although a treatment utilising this knowledge may be some years away, taking the first step is incredibly important – at Asthma UK we involve people affected by asthma in selecting the research that we fund, and they see the potential in this area of research and this researcher.

 

Improving ways to tackle the cold virus and stop this causing asthma attacks

  • Researcher: Dr Aurelie Mousnier is a researcher at Imperial College London
  • Start date: May 2016
  • How long will the project run for? 36 months
  • Project type: Project grant (funded in collaboration with the Medical Research Foundation (MRF))
  • Cost: £300,000 (Asthma UK's contribution is £90,000 – this was funded in collaboration with the MRF)

Project title: Analysis of rhinoviruses replication complexes to identify host cell targets for the development of antiviral drugs for the treatment of asthma exacerbations.

Many people with asthma find that viral infections, including the common cold, are a trigger for their asthma symptoms – estimates suggest that 85% of childhood and 60% of adult asthma attacks are triggered by viral infections. People with asthma also report that they often have much more severe symptoms when they catch a cold than people without asthma.

The common cold viruses are known as rhinoviruses.

Rhinoviruses, like all viruses, rely on infecting our own cells and 'hijacking' them to replicate themselves and survive. Our cells can usually detect when they've been invaded by a virus and turn on an antiviral defence mechanism.

Recent studies have shown that people with asthma have an antiviral defence mechanism that is not as effective – this may explain why people with asthma experience symptoms of a cold for longer, causing worse asthma symptoms.

Previous attempts to make drugs to tackle the cold virus have focused on tackling the virus itself. The researchers in this project propose to instead find a way to target the cells that the viruses are attacking with a treatment.

When viruses 'hijack' our cells, they use our cells' machinery to make proteins and replicate themselves. It may be possible to create a treatment that stops them from being able to do that by blocking the machinery, but without killing the cell. Additionally, if such a drug was inhaled directly into the lungs it has the potential to reach exactly where it's needed without having widespread effects on cells throughout the body.

This project represents an excellent opportunity to take the first step on an exciting journey towards improving symptoms and stopping asthma attacks in a large proportion of the 1 in 11 people in the UK who have asthma. If this is successful and lays the groundwork for the development of new treatments, this avenue of research may bear fruit in 5-10 years.

 

Looking at genes and the environment to work out what causes wheezing in preschool children and find treatments to prevent development of asthma

  • Supervisor: Dr Sejal Saglani
  • Type of grant: PhD studentship
  • Institution: Imperial College London
  • Grant amount: £100,000
  • Grant duration: 48 months
  • Start date: October 2016

Project title: Gene-environment interactions mediating preschool wheeze: the role of 17q21, farmyard microbes and innate cytokines

About one-third of children under the age of 5 experience wheezing and breathlessness, but not all of them go on to develop asthma by school age. Children with asthma have a reduced lung function by age 6 that is irreversible.

Recent research has shown that some children who wheeze when they have a cold or other viral infection before the age of three, who don’t go on to develop asthma and are thought to have outgrown it, are actually at an increased risk of developing lung conditions like COPD as adults.

There are no medicines to prevent the progression from wheeze to asthma, or ways to predict who will prevent lung damage later in life.

Previous studies have shown strong associations between a particular area of DNA, including two particular genes -  called ORMDL3 and GSDMB - and people who wheeze in early life and go on to develop asthma.

Additionally, we know that growing up on a farm protects children from developing asthma as the types of bugs that they breathe in seem to be protective.  Even those with the genetic susceptibility of the genes above halve their chance of developing asthma following viral wheezing early in life if living on a farm.

We therefore have evidence for the first time of an interaction between a patient’s genes and the environment that they are exposed to in determining the development of asthma. However, the biggest problem with all of the studies that have looked at genes and farming environments is that they only suggest a link, they do not prove causation, and they do not explain how the interactions are working to prevent asthma.

This research will further investigate the relationship between these two particular genes and the microbes present on farms that may prevent the development of asthma. Understanding how the two interact will also tell us more about the genes and why they have the effect that they do.

We currently have no way of identifying which viral wheezers will develop asthma and this project has the potential to change this.  We hope this project will pave the way to help researchers to develop a way to test which children with wheeze and breathlessness are likely to go on to develop asthma and other lung conditions. This project has a huge potential impact - it is the first step to identifying genetically susceptible children and giving them appropriate medicines that will protect them from developing asthma and lung damage and possibly move us towards treatments to mimic the effects of a farm environment and stop this from happening.

Improving diagnosis and the care that people with asthma receive

Developing better medicines and treatments for asthma