Brain inflammation

Inflammation is generally a protective process in response to an infection or an injury. However, if there is disease in the brain, inflammation can often make the disease worse.

For this reason, we need to understand the mechanisms of inflammation occurring in a diseased brain. When we understand these mechanisms, we will then work to find a way to block and prevent inflammatory damage.

Our research

The aim of our research is to understand fundamental mechanisms of inflammation and how they contribute to brain disease and pathology.

To address this, we investigate inflammation in a number of clinically important disease contexts, spanning acute brain injury and chronic neurodegeneration.

We also employ translationally-relevant approaches where mechanisms of inflammation are dissected in models of disease with validation in patient tissues and cohorts.

The overall objective of our research is to identify how immune pathways can be targeted as new treatments for brain disease.

Example ongoing projects in this area include:

  • Dissecting the immunological landscape in brain tumours to understand how cancer cells and immune cells communicate, and how the nature of this communication controls the trajectory of disease.
  • Identifying how the potent inflammatory cytokine interleukin-1 can be targeted in different diseases, such as neurodegeneration, stroke, cerebral malaria and brain tumours.
  • Understanding how the brain communicates with other organs in the body (for example, the gut) and how this interaction influences brain inflammation and injury after stroke.
  • Defining how inflammation at the border of the brain (the meninges) influences the development and progression of brain disease, and after traumatic brain injury.

Examples of our research

NLRP3 endosome paper

Inflammation is how the immune system protects our bodies against infection and damage. However, when inflammation is not controlled, it can contribute to many diseases including Alzheimer’s disease, stroke, and cancer. Learning more about how inflammation occurs at the microscopic level will allow us to gain a greater understanding of how we can target treatments for disease.

Inside immune cells there is a structure called the inflammasome that monitors its surrounding environment and remains inactive when the cell is functioning normally. For a cell to function normally, proteins and essential cargo are trafficked around the cell in carriers called endosomes. When traffic is disrupted, endosomes are stopped in their tracks and the cell undergoes a stress response.

We have shown here that the inflammasome can respond to this cell stress and become activated, triggering the release of harmful proteins, and causing an uncontrolled inflammatory response.

The research carried out in this paper allows us to understand more about how the inflammasome is activated. Further research into inflammasomes in this way will increase our current understanding of inflammation and how we can target inflammasomes in disease.

Investigators