Institute of Pharmaceutical Biology and Biotechnology

5th July 2024

As part of her career orientation internship Dora Molnar, a student from St. Willibrord Gymnasium in Bitburg, was able to join our working group. During this week, she gained exciting insights into everyday scientific laboratory work in human cell culture linking the theoretical knowledge of natural sciences from school into a translational context. In addition, Dora experienced how science combines analytical skills and creativity to achieve significant advances in the field of drug discovery.

________________________________________________________________

14th June 2024

There is a new research paper of the Kalscheuer group elucidating the antibacterial mechanism and molecular targets of synthetic nature-inspired bisindoles that exhibit potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), published in ACS Infectious Diseases (https://pubs.acs.org/doi/abs/10.1021/acsinfecdis.3c00657).  In this paper, mechanistic studies revealed that synthetic bisindoles impact the cytoplasmic membrane of Gram-positive bacteria by promiscuously interacting with lipid II and membrane phospholipids while rapidly dissipating membrane potential, providing a potential starting point for drug development in the fight against MRSA. While most pharmaceutical drugs are inhibiting protein targets, bisindole alkaloids are unusual as they interact with lipids, similar to certain antibiotics such as vancomycin. This study was conducted in close collaboration with the group of Thomas Müller (Institute of Organic Chemistry and Macromolecular Chemistry, HHU Düsseldorf) in context of the DFG Research Training Group GRK 2158 “Natural products and natural product analogs against therapy-resistant tumors and microorganisms: new lead structures and modes of action”.

Original publication:

Adeniyi ET*, Kruppa M*, De Benedetti S, Ludwig KC, Krisilia V, Wassenberg TR, Both M, Schneider T, Müller TJJ*, Kalscheuer R*. Synthesis of bisindole alkaloids and their mode of action against methicillin-resistant Staphylococcus aureus. ACS Inf. Dis 10, 1958–1969 (2024). https://doi.org/10.1021/acsinfecdis.3c00657

*These authors contributed equally. 

________________________________________________________________

7th June 2024

The Teusch research group is pleased to announce our new article entitled “Novel Histone Deacetylase (HDAC) Inhibitor Induces Apoptosis and Suppresses Invasion via E-cadherin Upregulation in Pancreatic Ductal Adenocarcinoma (PDAC)” which has been published in the journal Pharmaceuticals and is available online:

https://www.mdpi.com/1424-8247/17/6/752

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal form of pancreatic cancer characterized by therapy resistance and early metastasis, resulting in a low survival rate. Histone deacetylase (HDAC) inhibitors showed potential for the treatment of hematological malignancies. In PDAC, the overexpression of HDAC 2 is associated with the epithelial–mesenchymal transition (EMT), principally accompanied by the downregulation of the epithelial marker E-cadherin and increased metastatic capacity. Our study indicates that the HDAC inhibitor acts by suppressing tumor cell invasion via upregulating E-cadherin mediated by HDAC 2 blockade and by inducing cell cycle arrest leading to apoptosis via HDAC 6 inhibition. Moreover, a synergistic interaction with the chemotherapeutic drug gemcitabine could be demonstrated suggesting that selective HDAC inhibitors might represent a novel strategy for combination therapies of PDAC tumorigenesis and metastasis.

________________________________________________________________

23rd May 2024

As part of the Citizens' University, eight members of the public took part in the first round of a research project led by Prof Dr Rainer Kalscheuer, which was made possible by special funding from the HHU Rectorate. On a total of five course days, the citizens were able to gain a first-hand, practical insight into everyday scientific laboratory work and drug research and learn about the problem of antimicrobial resistance development. The citizens collected plant material from which they isolated endophytic fungi in the laboratory under the guidance of Prof Dr Rainer Kalscheuer and Dr Lasse van Geelen. In addition to carrying out a polymerase chain reaction and subsequent DNA sequencing for taxonomic identification of the fungi, the citizens tested extracts of the fungi for antibacterial activity. The endophytic fungi are now being further analysed for their antibacterial ingredients in the Kalscheuer working group. In this way, the committed citizens are not only supporting the research activities of the Kalscheuer working group in the long term, but may even have made a tangible practical contribution to the development of new, urgently needed active ingredients themselves in the future. Further information on our Citizens' University project "Endophyte Hunters" can be found under this link.

24th April 2024

On April 24th Nicole Teusch had the pleasure of presenting a new 3D organoid-on-chip model developed in collaboration with Dynamic42 GmbH to the scientific advisory board of the set foundation (Foundation for the Promotion of Research on Alternative Methods to Animal Experiments).

An inspiring afternoon with many exciting discussions and new ideas on modern alternative methods in pharmaceutical research.

________________________________________________________________

24th April 2024

See our recent contribution to an invited review article entitled “Architecture, function, regulation and evolution of α-glucans metabolic enzymes in prokaryotes” published in Chemical Reviews, which is one of the highest-ranked journals covering general topics of chemistry (IF 62.1). This review was written by Rainer Kalscheuer in collaboration  with colleagues from the University of the Basque Country, the Molecular Biology Institute of Barcelona (IBMB), and the University of Lille.

Original publication:

Cifuente JO, Colleoni C, Kalscheuer R, Guerin ME. Architecture, Function, Regulation, and Evolution of α-Glucans Metabolic Enzymes in Prokaryotes. Chem Rev. (2024) online ahead of print  (doi: 10.1021/acs.chemrev.3c00811).

________________________________________________________________