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PhD by Research Programme (Funded Research Programme - Infection and Immunity)

Employer
Global Academy Jobs
Location
Singapore
Closing date
Jan 31, 2017

Job Details

Research Project Title: New Antibacterial Targeting Potassium Channels

Source of Funding:R-SUG

Principal Investigator: Assistant Professor Luo Dahai, LKCMedicine

Co-supervisors: Professor George Chandy and Associate Professor Kevin Pethe, LKCMedicine

Project Description

a) Background  

The emergence and spread of multi-drug resistant (MDR) among pathogens is recognized as a global emergency for both hospital-acquired and community-acquired bacterial infections. Drug resistance among gram negative superbugs is particularly worrying because this class of pathogenic bacteria is usually intrinsically resistant to multiple antibiotic classes owing to the thickness of the cell membrane and the expression of efflux pumps. The aim of this project is to develop antibacterial that targets potassium (K+) channels.  In a recent Nature paper, potassium channels were shown to conduct long-range electrical signals within bacterial biofilm communities through spatially propagating waves of potassium, a process required for biofilm maintenance. Since K+ channels are also involved in many others cellular functions, including regulation of cytoplasmic pH, transmembrane electrical potential and turgor pressure maintenance, they represent an attractive target class for the development of next-generation antibacterials.

b) Proposed work 

1. Aim 1: Determine the role of potassium channels in gram negative bacteria. 
A dominant-negative strategy will be followed to delineate the function of potassium channel in the biology of gram negative bacteria. Using the knock-down construct, the role of the bacterial K+ channel will be determined.

2. Aim 2: Express and determine the structure of selected bacterial K+ channels. 
The expression of recombinant K+ channel will be valuable to perform panning experiments to rapidly screen peptide libraries for channel blockers whereas structure determination will guide future drug design.

3. Identification of K+ channel inhibitors. Recombinant K+ channel will be used in panning experiments or functional assay to identify potent inhibitors. Promising hits will be validated for cell-based activity against gram negative bacteria.

If you have questions regarding this project, please email the Principal Investigator, Assistant Professor Luo Dahai, at LuoDahai@ntu.edu.sg 

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