Grant: Operating Grant

The therapy of infectious diseases is under threat because antibiotic resistance is rising rapidly, while very few new drugs are under development or entering the clinic. One promising group of compounds are called host defence or antimicrobial peptides. These are small proteins that are produced by virtually all organisms, including plants, insects, and humans. Host defence peptides are a major component of the immune defences against infections because they lead to the death of microbial pathogens and modify immune responses. Our lab has been developing modified versions of these molecules as a new treatment for infections, and took first generation antimicrobial peptides into clinical trials. Here we propose to develop even more effective peptides to enable their successful clinical development as therapeutics for infections. We will investigate strategies to modify these peptides to prevent their usual destruction by enzymes called proteases that abound in the body. By making large numbers of these peptides and testing their activities, we will develop improved peptides for testing in the clinic. Specifically, we will determine whether these peptides work in combination with and improve the activity of conventional antibiotics. We will also continue to develop peptides that favourably boost the immune response of the host. In particular, we will try to understand what the peptides do to the cells of the immune system that make them effective in modifying our immune response. These peptides have enormous potential and we propose that by the end of the current grant funding period, they will enter into clinical trials to determine their potential for treating human infectious and inflammatory diseases.