Christopher Frøhlich
Postdoc. Research Fellow, Biomolecular and Structural Chemistry
Job description
Research Interests and Projects
As a researcher in the field of molecular biology, my primary interest lies in the intricate mechanisms of antimicrobial resistance (AMR), with a special focus on β-lactamases. My research journey, which began earnestly following the completion of my PhD, revolves around the evolution of these enzymes and their role in bacterial resistance.
Directed Evolution and Enzymology: One of my key interests is in directed evolution, a method that allows for the study of enzyme evolution in a controlled setting. This approach helps me understand how subtle genetic variations can lead to significant changes in enzyme activity and specificity, particularly in the context of antibiotic resistance. Additionally, my work in enzymology involves dissecting the kinetic and mechanistic aspects of β-lactamases, which is crucial for understanding how these enzymes confer resistance to β-lactam antibiotics.
Structural Investigations (X-ray Crystallography): Another significant aspect of my research is structural biology, specifically using X-ray crystallography. This technique provides a detailed view of the molecular structure of enzymes, allowing me to explore how structural changes in β-lactamases influence their function and interaction with antibiotics and inhibitors. These investigations are vital for designing effective inhibitors that can counteract antibiotic resistance.
Current and Future Projects: My current projects include exploring novel metallo-β-lactamase inhibitors, which are promising in the fight against carbapenem-resistant bacteria. In addition, by combining directed evolution, enzymology, and structural studies, I aim to develop a comprehensive understanding of these enzymes and design targeted strategies to mitigate their impact.
Current projects include:
a. Developing novel metallo-β-lactamase inhibitors.
b. Investigating β-lactamase-mediated resistance evolution.
c. Using directed evolution, enzymology, and structural analysis to explore enzyme adaptation in AMR.
d. Examining trade-offs in AMR evolution.
External Funding Awards:
12/2023 Young Investigator Grant, BATTLE: Antimicrobial resistance and Biofilm evolution (HelseNord)
02/2023 Marie Curie Awardee
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Research interests
First and last authorships (Updated 02/2014)
*Corresponding authorships †Last authorships
Lorentzen, M. Øyvind; Haukefer, Anne-Sofie; Johnsen, J. Pål, Fröhlich, Christopher (2024). The Biofilm Lifestyle Shapes the Evolution of β-Lactamase. Genome Biology and Evolution. doi: 10.1093/gbe/evae030*†
Fröhlich, Christopher; Bunzel, H. A.; Buda, K.; Mullholland, L. A., Van der Kamp, W. M., Johnsen, P.J.; Leiros H.-K.S ;Tokuriki, Nobuhiko (2024). Epistasis Arises from Shifting the Rate-Limiting Step during Enzyme Evolution. Nature Catalysis. doi: 10.1038/s41929-024-01117-4. https://rdcu.be/dzqjk*
Fröhlich, Christopher; Sørum, Vidar; Tokuriki, Nobuhiko; Johnsen, P.J.; Samuelsen, Ørjan (2022). Evolution of β-lactamase mediated cefiderocol resistance. Journal of Antimicrobial Chemotherapy. doi: 10.1093/jac/dkac221*
Fröhlich, Christopher; Chen, J. Z; Gholipour, Sevan; Erdogan. (2021) A. N; Tokuriki, Nobuhiko. Evolution of β-lactamases and enzyme promiscuity. Protein Eng Des Sel.;34, 10.1093/protein/gzab013
Fröhlich, Christopher; Gama J.A.; Harms K.; Hirvonen V.H.A.; Lund B.A.; van der Kamp M.W.; Johnsen P.J.; Samuelsen Ø. and Leiros H.-K.S. (2021) Cryptic β-lactamase evolution is driven by low β-lactam concentrations., mSphere, doi: 10.1101/2020.12.01.404343 *
Fröhlich, Christopher; Sørum, Vidar; Huber, Sandra; Samuelsen, Ørjan; Berglund, Fanny; Kristiansson, Erik; Kotsakis, Stathis D.; Marathe, Nachiket P.; Larsson, Joakim; Leiros, Hanna-Kirsti S. (2020). Structural and biochemical characterization of the environmental MBLs MYO-1, ECV-1 and SHD-1. Journal of Antimicrobial Chemotherapy. doi: doi:10.1093/jac/dkaa175.
Fröhlich, Christopher; Sørum, Vidar; Thomassen, Ane Molden; Johnsen P.J.; Leiros H.-K.S.; Samuelsen, Ørjan. (2019) OXA-48-Mediated Ceftazidime-Avibactam Resistance Is Associated with Evolutionary Trade-Offs. mSphere 2019; Volum 4 (2). ISSN 2379-5042.s doi: 10.1128/mSphere.00024-19.*
Teaching
KJE-3402 - Protein Structure
F1301- Farmasøytisk kjemi
Member of research group
CV
09/2021– 12/2023 Postdoctoral fellow with Prof. Pål Jarle Johnsen at Department of Pharmacy in Enzyme evolution and Structural biology at UiT- The Arctic University of Norway
09/2022– 09/2023 Postdoctoral fellow (50%) with Prof. Ole Andreas Økstad at Department of Pharmacy at Oslo University UiO
08/2017 – 08/2021 Ph.D. candidate in Structural Biology and Evolution with Prof. Hanna-Kirsti Schrøder Leiros at Department of Chemistry UiT- the Arctic University of Norway
12/2016 – 10/2017 Lab technician with Prof. Ørjan Samuelsen in the Microbiology Department at the University Hospital Northern Norway
09/2014 – 11/2016 M.Sc. in Analytical Chemistry at University of Applied Sciences Bonn-Rhein-Sieg (Germany)
07/2011 – 08/2014 B.Sc. in Pharmaceutical Chemistry at the University of Applied Sciences Cologne (Germany)
09/2009 – 11/2016 Lab technician in the QC laboratory at the vaccine production unit of MSD Animal Health (Germany)
08/2006 – 01/2009 Apprentice (chemical lab technician) at Rottendorf GmbH (Germany)