Lung infections kill one in three people who die from lung disease in the UK, and the rise of drug-resistant superbugs is making standard treatments less effective. This research focuses on a family of natural molecules called cationic host-defence peptides (CHDP)—part of the body’s early immune response—that can both kill microbes and dial inflammation up or down. The team will map the cellular pathways these peptides use to regulate airway lining cells during infection, then design new synthetic versions tailored to fight lung viruses such as influenza. If successful, the work could yield a new class of drugs that attack pathogens directly while also boosting the body’s own repair mechanisms, potentially bypassing the resistance strategies that defeat conventional antibiotics. This is fundamental science with a clear therapeutic target: understanding exactly how CHDP work at the molecular level is the necessary first step before any peptide-based treatment can be tested in people.
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Lung diseases are among the most common causes of ill-heath, accounting for 20% of deaths in the UK, with one third due to infectious diseases. The rise of superbugs is a ever increasing challenge, urgently requiring new treatments and a greater understanding of the body‘s natural protective mechanisms. Important components of our body‘s early defence system are cationic host-defence peptides (CHDP). Initially studied for their ability to kill bacteria and viruses, we have discovered many ways in which CHDP can alter inflammation, modulating the body‘s response to threat and damage, and the repair systems. CHDP are therefore drug templates with the capacity to kill microbes and enhance our natural protective responses. CHDP also offer the potential to circumvent the strategies that make superbugs resistant to our current conventional treatments. Building upon the foundation I have established with my recent research, I propose to: 1) determine the cellular pathways involved in the key activities of CHDP (particularly regulating the responses of airway lining cells to infection), 2) determine the role of these activities in protecting against the establishment of infection, and 3) design novel CHDP as potential therapeutics, with a particular focus on the treatment of pathogenic lung viruses, including influenza.
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