Development of fluorescent probes to determine live cell asymmetric membrane properties in pathogenic bacteria

Offer Description

One of the most pressing problems in health care is the concerning rise of antimicrobial resistances in pathogenic bacteria. Globally, 4.95 million deaths have been associated with antimicrobial resistance in 2019 while the WHO predicts 10 million deaths for 2050. New antibiotic therapy and targets are hence urgently needed to fight this global health problem. Because of their peculiar composition and properties, bacterial cell membranes constitute excellent targets for antibiotic therapy but bacteria developed resistance mechanisms that lead to alterations of membrane properties. The outer monolayer of bacterial membranes has usually a negative surface charge because of the high amount of negatively charged phospholipids such as phosphatidylglycerol or cardiolipin in Gram positive bacteria while Gram negative bacteria possess negatively charged lipopolysaccharides (LPS) on the outer monolayer leaflet. This negative surface charge makes bacteria susceptible towards cationic antibiotic peptides such as daptomycin or colistin which are considered last resort antibiotics. Interestingly, bacteria can alter outer monolayer surface charge by modifying their lipid composition and altering lipid structures to evade membrane damage induced by cationic peptides. In Staphylococcus aureus MprF1 adds positively charged Lysyl groups to phosphatidylglycerol, hence reducing the surface charge and rendering bacteria resistant towards multiple last resort antibiotic peptides. Similar processes occur upon membrane stress and alter the membrane composition in a dynamic way, interfering with cell growth, survival and fitness. Unfortunately, we do not know how both membrane monolayers are dynamically regulated.  

In this project, the postdoctoral researcher will therefore develop genetically encoded fluorescent peptides that simultaneously quantify inner and outer monolayer surface charge in live bacteria. These probes will be calibrated on membrane models such as Giant unilamellar vesicles of known surface charge and lipid composition, and further validated in live bacteria. In a long term these probes should allow us to understand antimicrobial resistance towards last resort cationic peptides and its dynamic development.

This postdoctoral position is funded for 3 years. The candidate will have experience in molecular biology and microbiology. Experience in microscopy, fluorescence techniques, membrane biophysics or analytical chemistry is a bonus. The candidate will be trained in advanced imaging techniques such as fluorescent lifetime imaging, anisotropy imaging, two-photon imaging, spectral imaging and related image analysis and develop a deep understanding in peptide/membrane interactions and related resistance mechanisms. 

The postdoc will work in a vibrant, multidisciplinary team that has experience in molecular and clinical approaches. She/He will join the team at the Woluwé-Saint-Lambert campus of UCLouvain University in Brussels, Belgium. 

If you are interested in this project, please send a C.V. and a motivation letter to [email protected]. Please indicate in the motivation letter how well your qualifications match the position.

Where to apply

E-mail [email protected]

Requirements

Research Field Biological sciences » Biological engineering

Education Level PhD or equivalent

Research Field Pharmacological sciences » Other

Education Level PhD or equivalent

Research Field Physics » Biophysics

Education Level PhD or equivalent

Skills/Qualifications

Molecular Biology, Microbiology, Experience in microscopy and/or fluorescence spectroscopy, Membrane Biophysics

Specific Requirements

Please send a C.V. and a motivation letter to [email protected]. Please indicate in the motivation letter how well your qualifications match the position.

Languages ENGLISH

Level Excellent

Additional Information

Website for additional job details https://uclouvain.be/en/research-institutes/ldri/facm-in-detail.html

Work Location(s)

Number of offers available 1

Company/Institute UCLouvain

Country Belgium

State/Province Brussels

City Brussels

Postal Code B-1200

Street Avenue Mounier 73

Contact

State/Province Brussels

City Brussels

Website https://uclouvain.be/en/research-institutes/ldri/cellular-and-molecular-pharmacology-facm.html

Street Avenue Mounier 73

Postal Code 1200

E-Mail [email protected]

Phone 243661021