Objectives: To determine the mechanism ClpXP protease contribute to intrinsic resistance to cell wall antibiotics and the role of autolysins in killing by b-lactams.

Expected Results: 1) The molecular mechanism behind the emergence of Clp mutants emerge against clinically applied antibiotics (e.g., β-lactams, vancomycin, daptomycin) has been elucidated, 2) The role of autolysins in b-lactam mediated killing of G+ pathogens (MRSA) has been determined.

PhD fellowship in “Bacterial Antibiotic Resistance Mechanisms” | EURAXESS (europa.eu)

Objectives: To construct a map of interactions of major cell wall proteins including the PBPs and those involved in teichoic acid synthesis.

Expected results: 1) A protein interaction map pointing to key interaction points linking cell envelope biosynthesis with central components of the cell division machinery, 2) prediction of key proteins to be mined as potential hits.

Objectives: To identify novel antimicrobial activities from variants of poorly explored classes of known metabolites and of metabolites predicted not to be associated with known classes.

Expected Results: 1) Chemical structures of at least 3 metabolites and 2) their antimicrobial activities of the identified molecules.

Position available at Naicons, IT | EURAXESS (europa.eu)

Objectives: To determine the 3D structures by X-ray crystallography of different LD-transpeptidases from C. difficile (Ldt1, Ldt2, Ldt3) in order to unveil their molecular mechanisms as well as a starting point to develop efficient inhibitors. To identify inhibitors of at least one LD-transpeptidase and assess the impact on sporulation and resistance to cell wall antibiotics in vancomycin-resistant C. difficile.

Expected Results: 1) Structure will have been determined of at least two LDTs and 2) four small molecule inhibitors have been identified and tested.

PhD Studentship in the HORIZON-MSCA-2022-DN Doctoral Network “CLEAR” | EURAXESS (europa.eu)

Objectives: To demonstrate efficacy of computer assisted drug design (CADD) methods on antimicrobial targets in the bacterial envelope with focus on LD-transpeptidase from C. difficile. Preliminary synthetic optimization of hits to select most promising for further development.

Expected Results: 1) To have identified novel inhibitors of LD-transpeptidases of C. difficile and of two targets identified in the project; 2) To have derivatized hits obtained by analysis of at least one LD-transpeptidase.

Early stage researcher/PhD student position at Latvian Institute of Organic Synthesis, MSC project CLEAR | EURAXESS (europa.eu)

Objectives: To identify and characterize compounds that maintain ticagrelor antibacterial activity but are devoid of antiplatelet effect among a hundred of ticagrelor-derived pyrimidine compounds synthesized by ULiège. About twenty of these molecules, triazolo-pyrimidines and purines, display potential antibacterial activity as ticagrelor. All of these molecules are patented.

Expected Results: 1) Ten derivatives of ticagrelor with antibacterial activity but lacking the antiplatelet activity have been identified and 2) To derivatives have been characterized in detailed in in vivo assays.

Objectives: To determine the mode of action in penicillin/β-lactamase inhibitor killing of MRSA and MDRSE. To identify the optimal penicillin/β-lactamase inhibitor combinations (with and without other potentially potentiating drugs) and dosage regimens using checkerboard assays. To access the efficacy of the best penicillin/β-lactamase inhibitor combination(s) in in vitro and animal models of biofilm- and non-biofilm-related infections.

Expected Results: 1) The mode of action has been identified; 2) The efficacy of the best combination(s) has been tested.

Objectives: To determine if combined use of antibiotics and phages can enhance bacterial killing with reduce resistance development, and determine the overlaps in molecular targets of phages and antibiotics, respectively.

Expected Results: 1) Identification of combination treatments that enhance bacterial killing with limited resistance development 2) Knowledge on bacterial pathways that may be triggered to enhance phage therapy against G+ pathogens.

PhD9 – Phage combination therapy

Project Description

Effective treatment of staphylococcus aureus is today currently hindered by the emergence of multi-drug resistant variants and have become a global issue for the clinic. Previously, the use of the drug methicillin and vancomycin was the last line of treatment, however, with the emergence of methicillin- and vancomycin resistant staphylococcus aureus, our options today are limited. The need for new antibiotics and new therapeutic alternatives therefor must be investigated to combat this pressing issue. One possibility is phage therapy, a previous used treatment alternative which vanished with the emergence of antibiotics but have recently reemerged to become a promising candidate. By using bacteriophages that specifically infect staphylococcus aureus, we can alleviate the occurrence of new mutations from use of antibiotics and hopefully solve this issue. 

The aim of my project is to identify bacterial pathways or factors that are determining for the efficacy of phage infection and thereby for the use of phages in phage therapy. To do so, I will screen for a large library of drugs which could support phage infection and identify bacterial pathways that may be triggered to enhance phage mediated killing. Hopefully, this would also lead to identification of secondary phage receptor sites as the wall-teichoic acid is currently the only known receptor site for phage uptake. My Secondment will be conducted at NAICONS (Italy) which is where I will be screening their library of drugs for suitable candidates that could enhance phage killing.

Frederik Pedersen

Email: f.pedersen@sund.ku.dk

Affiliation:
University of Copenhagen
Department for Veterinary and Animal Sciences
Stigbøljen 4
1870 Frederiksberg C 

Education and Experience: 

In June 2021, I acquired a BSc in biology at Linköping’s University, Sweden. During my bachelor’s, I got to experience everything related to cell- and molecular biology, pharmacology, microbiology and physiology. At the time, I really enjoyed medical physiology and therefore made it my specialization. For my bachelor’s thesis, I joined the group of Professor Jordi Altimiras in organ physiology. The project was based on previous data which indicated to survive birth, the organs of neonates must drastically develop to survive leaving the egg or the mother’s womb. My project was therefore to investigate and confirm whether there was a difference in organ mass leading up to hatching by dissecting and analyzing red junglefowls (Gallus Gallus) pre- and post-hatchlings. 

I’ve always loved to learn new things and explore new areas and, I knew from my bachelor’s that I also had a big interest for systems biology, immunology and microbiology. With this, I wanted to expand on my knowledge in medical physiology. I therefore achieved in 2023 a master’s in Immunology and Microbiology with an emphasis on host-pathogen interactions at Uppsala University, Sweden. During my Master’s, I joined Associate Professor Erik Holmqvist’s group at Uppsala University in molecular microbiology. My project revolved around post-transcriptional regulation of Salmonella pathogenicity Island 2 (SPI-2), one of the key regions of genes involved in Salmonella pathogenesis.  More specifically, my project was to investigate whether there was an interaction between the global RNA binding proteins Hfq and ProQ on the phoP 5’UTR. My work also led me to investigate the small RNA ArcZ, to see if it repressed the expression of phoPQ mRNA and if the binding was dependent on Hfq. 

During and after my master’s studies, I also worked in the industry for Olink Proteomics as a laboratory Engineer in proteomics. I always knew I wanted to pursue a PhD and knew it had to be related to microbiology and host-pathogen interactions. After a year in the industry post-graduating, I finally found a PhD I really wanted and started 1^st of May 2024 in Hanne Ingmer’s group at Copenhagen University as part of the CLEAR project. 

Objectives: To develop novel phage based endolysins as antimicrobials against C. difficile and MRSA

Expected Results: 1) At least four endolysins discovered with efficacy against MRSA and C. difficile and 2) two endolysins characterized in gut models and by 3D structure (together with PhD5).

https://euraxess.ec.europa.eu/jobs/190023