Project Background:
Endotoxins are substances that are toxic to mammals (including humans) because they elicit an extremely strong immune response. This response, when untreated, can escalate to a point of no return, where the massive release of cytokines triggers septic shock and later, multi-organ failure [1].
In a recent project, we have discovered a 30-residue peptide that can bind the major endotoxin from Gram-negative bacteria, the bacterial lipopolysaccharide (LPS) with extreme affinity [2]. The peptide, and its possible biotechnology applications in both endotoxin detection and endotoxin removal, has been patented by the University of Oslo in 2022. It is worth noting that endotoxin detection and removal products have an extremely high market value, and that existing solutions are far from perfect in their performance [3].
Aims of this project:
The purpose of this MSc project is to shed light on the molecular reasons for the high affinity to LPS. You will purify LPS from different bacterial species, and test binding using the peptide. You will introduce mutations in the peptide to define the binding site better; in parallel, NMR experiments and other biophysical methods will help you to both define the binding site, and to test what substances might interfere with binding. You will work closely with researchers in the Linke group, and with companies that are interested in developing products based on our peptide for different biotechnology applications.
Methods:
- Microbiology methods: cultivation of different species (Biosafety level 2)
- Biotechnology methods: endotoxin assay development
- Site-directed mutagenesis
- Endotoxin purification
- NMR
Requirements:
This project is suitable for students of the study programs Molecular Biology/Biochemistry, Cell Biology/Physiology, or Genetics/Developmental Biology - but students from all study programs and from other departments are welcome to contact us. We prefer candidates to join the group early in their MSc program and to work on their thesis project part-time, in parallel to their course work. Some background in Microbiology, Chemistry or Biochemistry is an advantage.
Supervisors:
Prof. Dirk Linke, Dr. Athanasios Saragliadis
About the group:
The research group of Prof. Linke is a very international and interdisciplinary environment, and is part of the EVOGENE section. The working language in the lab is English. The group excels in microbiology, biochemistry, and biotechnology methods, but we offer thesis topics for all MSc study programs. More information (also about other potential projects interesting for MSc students) can be found here:
https://www.mn.uio.no/ibv/english/research/sections/evogene/groups/linke/index.html
References
[1] Cavaillon JM. Exotoxins and endotoxins: Inducers of inflammatory cytokines. Toxicon. 2018 Jul 1;149:45-53.
[2] Hatlem D, Christensen M, Broeker NK, Kristiansen PE, Lund R, Barbirz S, Linke D. A trimeric coiled-coil motif binds bacterial lipopolysaccharides with picomolar affinity. Frontiers in Cellular and Infection Microbiology. 2023 Feb 16;13:1125482.
[3] Cao Y, Zhang Y, Qiu F. Low endotoxin recovery and its impact on endotoxin detection. Biopolymers. 2021 Nov;112(11):e23470.