Novel antimicrobial peptides from fish blood

The proposal aims to develop a new arsenal of antibacterial agents in order to combat the rapid emergence of antibiotic resistance in pathogens worldwide. Antimicrobial peptides (AMPs) are naturally occurring compounds against microorganisms including bacteria. AMPs have been studied in many organisms but efforts on the systematic identification of AMPs in fish have been lagging. Our lab has recently collected blood plasma from medaka fish and, by using mass spectrometry, identified 6399 unique sequences, among which 430 potential AMPs are bioinformatically predicted. One of them shows a broad-spectrum toxicity on pathogenic bacteria the specific suppression of the envelope stress responses (ESR). The serendipitous discovery of this AMP illustrates the usefulness of this database as a resource for AMP mining. Building on this exciting foundation, we propose to conduct a systematic screening of the rest of our propriety peptide database for antibacterial activities, and thereby generate a set of novel AMPs for future investigation. In parallel, we will advance our understanding of the AMP initially identified and path the way of its clinical translation. To achieve this, this PhD project will produce an antibody against this AMP so that we can detect this peptide in fish and other organisms, and to monitor its expression in response to bacterial infection. We will also validate the role of this AMP in modulating the ESR of Gram-negative bacteria, and hence establish that this is a druggable pathway for the development of future antibacterial therapeutics. Taken together, this project will greatly extend our preparative work on fish blood peptides by creating a pipeline of novel AMPs, of which one compound will lead its way towards mechanistic characterization and clinical applications.

City University of Hong Kong is a foremost university in the exciting city of Hong Kong, one of the most international cities in Asia. Our university is currently placed 7th in the world’s young universities (below 50 years old) and 47th in the QS ranking of world universities. We all know this kind of ranking is quite meaningless, but are nonetheless very proud of these achievements.