Background:
Antimicrobial resistance is on the rise and has been so since the first antimicrobials were applied in 1937 [1]. In the light of this ongoing crisis, the World Health Organization (WHO) has defined a list with bacterial pathogens that should be prioritized as targets for developing new therapeutic approaches [2]. These include many bacteria that were previously considered relatively harmless and easy to treat, but that have now become major killers due to their ability to resist almost all known antibiotics. Amongst the bacterial species that are listed as “critical priority” are Acinetobacter baumannii, Pseudomonas aeruginosa, and many Enterobacteriaceae.
Bacterial adhesion to surfaces and host tissues is the first step of host colonization and infection. The aim of our research is to understand the details of this process, and by doing so, to learn how to control and inhibit it. Bacterial surface proteins known as adhesins initiate host-microbe interactions and are an attractive target for novel antibacterial compound discovery. We have previously developed assays for the discovery of small-molecule inhibitors of bacterial adhesins to their corresponding eukaryotic binding partners [3].
Aims of this project:
The aim of this MSc project is to clone and express a set of bacterial adhesins from enterobacterial pathogens included in the WHO priority list. These adhesin molecules will be used in binding assays with receptor proteins or with eukaryotic cells to better understand their mechanism of action, and for testing the efficiency of previously identified inhibitor molecules.
Methodology:
Microbiology, Gene manipulation (cloning), Protein expression and purification, Biophysical characterization (Surface plasmon resonance), Microplate-based assay development, Microscopy
Work Place and Environment:
https://www.mn.uio.no/ibv/english/research/sections/evogene/groups/linke/
The Linke group works on interdisciplinary projects related to bacterial infections and biotechnology, and is part of the EVOGENE section at IBV. The group members have diverse scientific backgrounds and career stages. The working language in the group is English.
Requirements:
This project is best suited for students of the study programs Molecular Biology/Biochemistry, Cell Biology/Physiology, or Genetics/Developmental Biology - but students from all study programs and form other departments are welcome to contact us. A strong background in Microbiology or Biochemistry is an advantage.
Literature:
1. Davies J and Davies D (2010) Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev 74:417-33. doi: 10.1128/MMBR.00016-10
2. WHO (2021) Antimicrobial resistance. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
3. Saragliadis A and Linke D (2019) Assay development for the discovery of small-molecule inhibitors of YadA adhesion to collagen. Cell Surf 5:100025. doi: 10.1016/j.tcsw.2019.100025