Host Defence Peptides as novel modulators of autophagy in Inflammatory Bowel Disease
  Increasing numbers of patients are diagnosed with inflammatory bowel disease (IBD) each year, both in the United Kingdom and worldwide. Most drugs in current use for the treatment of IBD target the immune system to reduce inflammation and induce remission, however their effects are suboptimal and diminish over time. Development of new therapeutics that can more effectively treat this condition is a priority, and with this, a comprehensive understanding of how these new drugs work is required.
Genetic studies have improved our understanding of what causes one of the two main forms of IBD known as Crohn’s Disease (CD). Key areas identified include the body’s front-line defence against infection (innate immunity) and an intracellular process called autophagy. The innate immune system protects us against infectious organisms such as bacteria and viruses. Autophagy can help to move infectious organisms around the interior of a cell to specialised areas called lysosomes, where the organisms are rapidly destroyed. There is a longstanding belief that that bacterial infection is associated with the development of CD. Numerous studies have identified a specific organism known as adherent, invasive Escherichia coli (AIEC) in adults and children with CD, and recent work has shown that abnormal autophagy (due to gene mutations) allow these E. coli bacteria to remain unchallenged in the lining of the gut and increase in number, causing sustained inflammation.
A family of naturally occurring small molecules called cathelicidins are a key part of the innate immune system in humans. Cathelicidins have powerful antibacterial and antiviral properties and can influence the outcome of an infection by altering the inflammatory response. Recent work has indicated that the human cathelicidin, LL-37, can stimulate autophagy. Therefore, determining how this small molecule stimulates autophagy at the molecular level may offer a powerful new therapeutic approach to a) reduce the ability of AIEC to reproduce inside cells and to b) dampen down a damaging inflammatory response. We believe that modifying LL-37 to enhance its ability to induce autophagy could therefore provide a valuable new approach to developing treatments for CD.
This is a Daphne Jackson Fellowship funded by Medical Research Scotland.

  • Start Date:

    1 October 2019

  • End Date:

    31 December 2022

  • Activity Type:

    Externally Funded Research

  • Funder:

    The Daphne Jackson Trust

  • Value:


Project Team