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- Heinrich Heine University cooperates with numerous research institutions and networks beyond the boundaries of the faculties. The HHU's affiliated institutes in particular act as a link to industry. As independent institutions, they maintain close contact with research in the faculties and participate in the training of young academics.
- One of our foci today, linking all faculties, are the Life Sciences. Cross-departmental, joint study programmes (such as Business Chemistry) are one of our major strengths.
- The ZIM is a central operating unit of the Heinrich Heine University. It is a service and competence center for all aspects of digital information supply and processing, digital communication and the use of digital media.
Recent Submissions
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(2026)
Öffentlicher Teil des Abschlussbericht des GRK 2158 "Naturstoffe und Analoga gegen Therapie-resistente Tumoren und Mikroorganismen: Neue Leitstrukturen und Wirkmechanismen", 270650915
(2026-06-23) Gohlke, Holger; Kalscheuer, Rainer; Wesselborg, Sebastian; Holz, Martina
Therapieresistenzen stellen eine der größten Herausforderungen der modernen Medizin dar: Sowohl Krebszellen als auch krankheitserregende Mikroorganismen können sich so verändern, dass bewährte Medikamente ihre Wirkung verlieren. Das Graduiertenkolleg (GRK) 2158 an der Heinrich-Heine-Universität Düsseldorf widmete sich daher der Frage, wie solche Resistenzen besser verstanden und überwunden werden können, um neue, wirksamere Therapieansätze zu entwickeln. Im Mittelpunkt der Forschung standen natürliche und davon abgeleitete Wirkstoffe, die gezielt zentrale Schwachstellen von Tumorzellen und Bakterien angreifen. Dazu gehörten insbesondere Naturstoffe aus marinen Organismen und ebenso neu entwickelte chemische Verbindungen. Die Forschenden untersuchten, wie diese Substanzen zelluläre Prozesse wie den programmierten Zelltod, Reparaturmechanismen von DNA, Zellstoffwechsel, Autophagie oder das Immunsystem beeinflussen. Ein besonderer Fokus lag auf epigenetischen Mechanismen, also der Regulation von Genaktivität, sowie auf bakteriellen Schutzmechanismen gegen Antibiotika. Durch die enge Zusammenarbeit von Chemie, Medizin, Biologie, molekularer Bioinformatik und Strukturbiologie konnten neue Wirkstoffkandidaten identifiziert, gezielt verbessert und ihre Wirkweise detailliert aufgeklärt werden. Mehrere Ergebnisse sind so vielversprechend, dass sie bereits zu Patentanmeldungen geführt haben, ein wichtiger Schritt auf dem Weg von der Grundlagenforschung hin zu möglichen neuen Medikamenten. Darüber hinaus wurden innovative Software- und Datenbanklösungen entwickelt, die offen zugänglich sind und die Wirkstoffforschung weltweit unterstützen. Neben den wissenschaftlichen Ergebnissen leistete das GRK einen wichtigen Beitrag zur Ausbildung des wissenschaftlichen Nachwuchses. Promovierende wurden interdisziplinär ausgebildet, international vernetzt und früh an eigenständige Forschung herangeführt. Insgesamt zeigt das GRK 2158, wie durch vernetzte Grundlagenforschung neue Ansätze zur Bekämpfung von Krebs und Infektionskrankheiten entstehen können, mit langfristiger Bedeutung für die Gesundheit der Gesellschaft.
Public part of the final report for the DFG project "Targeting protein-protein interactions within the autophagy-inducing ULK1 complex for cancer therapy", STO 864/4-3 and GO 1367/4-3, 267192581.
(2026-06-23) Stork, Björn; Gohlke, Holger
(Macro-)Autophagy is a major intracellular recycling pathway mediating the removal of longlived or damaged proteins or organelles. Autophagy occurs at basal levels in most cell types and ensures cellular homeostasis. Additionally, autophagy is actively induced under stress conditions such as nutrient or growth factor deprivation, hypoxia, treatment with chemotherapeutics, protein aggregation, or infection with intracellular pathogens. The dysregulation of autophagy is associated with various diseases, including cancer, infectious diseases and neurodegenerative diseases. In cancer, autophagy plays a rather ambivalent role, depending on the stage and type of cancer. Accordingly, both tumor-suppressing and -promoting activities of autophagy have been described. In recent years, the molecular machinery controlling this process has been identified and characterized.
The ULK1 complex, consisting of the Ser/Thr kinase ULK1 and the associated proteins ATG13, ATG101 and FIP200/RB1CC1, represents a central element for the induction of autophagy. In previous DFG-funded projects, we were able to characterize the protein-protein interactions (PPIs) within the ULK1 complex. With this proposal, we aimed to utilize this knowledge and develop small molecules or peptidomimetics that interfere with PPIs of the ULK1 complex. In addition, the identified inhibitors should be tested for their autophagy-inhibiting/modulating potential and for their efficacy in preclinical model systems.
Using both an in vitro high-throughput and a virtual structure-based screening approach, we identified four small molecules (AFS30, AFS32, KMG24, KMG28) that interfere with the ATG13-ATG101 interaction within the ULK1 complex. We were able to show that these four compounds inhibit the cellular ATG13-ATG101 interaction and significantly reduce autophagic activity. The two AFS compounds preferentially bind to ATG13 and interfere with the interaction allosterically, whereas the two KMG compounds preferentially associate with ATG101 and act via an orthosteric mode of action. Additionally, AFS30 and AFS32 sensitize nutrient-restricted cancer cells to apoptosis. All compounds exhibit suitable physicochemical properties that support their further development as therapeutic agents. Therefore, we propose that these validated hits represent a promising step for the further development of autophagy inhibitors targeting the ATG13-ATG101 heterodimer.
MD data for "Minimalistic intrinsically disordered DNA enzymes for programmable DNA editing"
(2026) Heße, Robert; Gertzen, Christoph; Gohlke, Holger
Circadian rhythms of neuronal and astrocytic glutamate transporters in the suprachiasmatic nucleus of mice
(2026) Haidar, Hussein; Ali, Amira A. H.; von Gall, Charlotte; Tundo-Lavalle, Federica
Retinal ganglion cells release glutamate at their synapses, transmitting visual signals via the optic nerve to brain regions involved in vision and light-dependent functions. Glutamatergic input to the circadian pacemaker, the suprachiasmatic nucleus (SCN), is essential for photoentrainment of circadian rhythms. Glutamate transporters are crucial for efficient transmission in the tripartite synapse formed by presynaptic terminals, postsynaptic neurons and astrocytes. However, it remains unclear whether this glutamatergic synapse is modulated by rhythmic environmental lighting conditions. In this study, neuronal (VGLUT1 and VGLUT2) and astrocytic (GLAST) glutamate transporters of 8-12 weeks old male C57Bl/6J mice were analyzed in the SCN of mice exposed to different lighting paradigms: a standard 12:12-hour light-dark cycle (LD), constant darkness (DD) and constant light (LL), using immu-nofluorescence and confocal laser microscopy. All three transporters exhibited time-of-day–dependent rhythms: VGLUT1 and GLAST peaked during the light phase, while VGLUT2 peaked during the dark phase. This suggests that VGLUT1 and GLAST are more strongly coupled and that VGLUT2 is a complementary system, so that the strength or efficiency of the light information can be modulated depending on the time of day. These rhythms persisted under DD and LL, indicating robust circadian control. Our study thus supports the hypothesis that the circadian system may regulate its own input.
Revised data for "Mechanistic Insights into the Structural Asymmetry of the LanFEG Transporter NisFEG in Lantibiotic Immunity"
(2026) Cea, Pablo; Gohlke, Holger
Nisin is one of the best studied antimicrobial peptides. Still, how nisin-producing strains can protect themselves against nisin’s bactericidal effects is only partially understood. Located within the nisin biosynthesis operon, the heterotetrameric ABC transporter NisFEG transports nisin to the extracellular environment, granting autoimmunity to the producer strain. NisFEG belongs to the LanFEG family of ABC transporters, members of which are found in some lantibiotic-producing bacterial strains. However, their structure has not been elucidated. In this work, we constructed a full atom model of NisFEG in the ATP-bound conformation. The architecture of the complex reveals a narrow contact interface between the two transmembrane chains, with prominent lateral clefts, similar to those observed in other exporters of hydrophobic compounds. Through molecular dynamics (MD) simulations, we observed that one of the most conserved elements of the LanFEG family, the E-loop of the nucleotide-binding domain, interacts preferentially with a small intracellular helix of the NisG transmembrane chain. By combining co-solvent MD simulations and predictions of the binding mode of the terminal segment of nisin, we could identify a putative interaction surface, located predominantly on NisE. Our results suggest that nisin extrusion operates in an asymmetric manner, where contacts between the E-loop and NisG are the driving force for the conformational changes triggered by ATP hydrolysis, whereas the NisE subunit is the main mediator of interactions with the lantibiotic. This functional asymmetry could explain why the LanFEG family has evolved two distinct transmembrane chains, where each one was selected to perform a single step in an optimal way, maximizing the immunity of lantibiotic-producing bacteria.