Associate Professor
Pui Lai Rachel Ee
Deputy Head, Department of Pharmacy & Pharmaceutical Sciences, National University of Singapore
Title of the talk: Peptide Nanonets as Antimicrobial and Anti-inflammatory Agents
Abstract
Antimicrobial peptides (AMPs) are mostly known to modulate host innate immunity as discrete molecular species. A small subset of AMPs, however, participate in nanonetting to entrap microbial cells, effectively arresting their dissemination and render them more vulnerable to locally secreted microbicides. By studying a series of β-hairpin peptides, our group is interested in understanding the principles guiding selective nanonetting and spatiotemporal control over microbial killing of AMPs. A library of 15 to 16 residue-long synthetic β-hairpin peptides was constructed with the ability to self-assemble into nanonets in response to the presence of bacteria. This dual antimicrobial function enables the manipulation of the antimicrobial profile of the peptides as well as more complete killing before entrapped microbes can escape from the mesh. The membrane components lipoteichoic acid (LTA) and lipopolysaccharide (LPS) were shown to play a major role in determining the nanoletting capacity as triggered by Gram-positive and Gram-negative bacteria respectively. De novo designed nanonets displayed improved antimicrobial potency against resistant clinical isolates and had robust stability against proteolytic degradation. Remarkably, these peptide nanonets were also able to capture free negatively charged endotoxins and proinflammatory cytokines via electrostatic interactions, hence mitigating downstream inflammatory events. Finally, bacterial entrapment by peptide nanonets delayed the development of resistance among pathogenic bacteria against clinically relevant antibiotics through a general reduction in bacterial motility. This presents a fresh perspective in resistance circumvention in our fight against antibiotic resistance.
Biography
Rachel Ee is Associate Professor, Deputy Head of Research and Founding Director of the Pharmaceutical Science Program in the Department of Pharmacy & Pharmaceutical Sciences at the National University of Singapore (NUS). Her research is focused on understanding the chemical and biophysical interplays between peptides/hydrogels and bacteria and innovations in peptide chemistry for potential clinical translation of peptide therapeutics. Her programme has been funded successfully for 16 years via multiple external grant agencies and private companies. From the early establishment of her expertise in drug delivery, in particular hydrogel formulation, she has published widely in high impact journals such as Biomaterials, Angewandte Chemie Int Ed, NanoToday, Nature Biomedical Engineering and Advanced Drug Delivery Reviews. This led to several industry collaborations and co-creation of 2 patents. Her research on antimicrobial peptides (AMPs) was published in Nature Biomedical Engineering, Advanced Functional Materials, Biomaterials etc, that consolidated the knowledge of applying AMPs and peptide nanonets in clinical settings. She was the recipient of the Asian Universities Alliance (AUA) Scholarship in 2020 and DAAD (German Academic Exchange Service) Research Fellowship in 2014.
Publications: Google Scholar Website ORCID