Title: 1. The application of peptide nucleic acid (PNA) in antibacterial discovery; 2. Antisense in Bacteria; 3. Synthetic Biology

Presenter: James Edward Morgan Stach; Edward Liam Good; Pinghua Liu

University: Newcastle University; The Royal Veterinary College; Boston University

Time: 9:00-12:00, March 11, 2013

Venue: Room A203, Institute of Microbiology, Chinese Academy of Sciences

Abstract: Peptide nucleic acid (PNA) is a DNA mimic with properties suited to the development of gene-specific antisense agents. Research in our labs has shown that PNAs can be used as antibacterial agents, but also to identify novel protein targets that are amenable to antimicrobial drug development. In this talk, I will use different examples to highlight the antibacterial discovery potential of these compounds. Particular emphasis will be given to application of PNAs to antibacterial natural product discovery, the development of species-specific antimicrobial agents, and PNA resistance studies that may lead to the development of second generation PNAs that are suitable for clinical development. --- James Edward Morgan Stach

Bacterial resistance to conventional antibiotics is a serious health problem. Unfortunately, only a few truly new antibiotics have been discovered during the last half century. Therefore, there is a need for new strategies. Liam's laboratory works in the general area of RNA biology and has pioneered the idea of using “antisense agents” as antibacterials. Whereas conventional antibiotics typically inhibit protein targets, antisense agents target “sense” messenger RNAs. As potential drugs, antisense agents can inhibit a wider range of target genes and act with improved species selective effects. This should enable pathogen targeting without damage to the normal flora. We are working with medicinal chemists to improve cell uptake and distribution properties.--- Edward Liam Good

Broadly speaking, the Liu laboratory is interested mechanistic studies of natural product biosynthesis, their production through synthetic biology, and the creation of conditional knockout models for biomedical applications. In the presentation, I will make use of two recent examples in the Liu laboratory:

Ergothioneine biosynthetic studies and their production through synthetic biology: Ergothioneine and ovothiol are two thiol-imidazole containing natural products isolated. They were widely applied as key components in many commercial products with a market size of billions of dollars. I will present our most recent efforts on ergothioneine biosynthetic studies and their production through metabolic engineering.

Developing chemical genetic tools for epigenetic studies. Epigenetic regulation (DNA, RNA, and protein modifications) is one of the frontiers at the interface of chemistry and biology. One of the long-term goals in the Liu laboratory is to study the chemical basis of biologic clock and their roles in development and ageing. The most challenging task to address this issue is to develop transgenic animal models that allow reversible and temporal control of gene functions. I will discuss our most recent efforts on addressing this issue using synthetic biology approaches.---Pinghua Liu