Monday Afternoon Science Seminar

Monday Afternoon Science Seminar (MASS): MASS is an interdisciplinary platform to spread the message of science. In up to 30 minutes selected speakers will talk about their research interest and their latest exciting results. The seminars will be presented in English and will be introduced for non-professionals, professionals and others. To warm up our afternoons, we will begin with online science talks of our HMU staff.


14.11.2022, 17:00 h, Room 417 Schiffbauergasse
Professor Paul Baird from the University of Melbourne, Australia, visiting Professorial Fellow at the Institut für Humangenetik, Universität Regensburg

Abstract: Multiple sources of big data, particularly in the area of genetics have allowed identification of multiple genes and key gene networks involved in disease. To gain a more holistic view of disease causation and its progression requires that we also consider data from other sources including environmental risk factors and demographics. Analysis of these large quantities of data necessitates the use of advanced bioinformatics, machine learning and artificial intelligence. I will provide examples from eye diseases as to how these advances will help in our understanding of disease to personalize treatment approaches for the patient.


28.11.2022, 17:00 h, Room 417 Schiffbauergasse
Professor Tilman Grune, director of German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany will talk about ‘Oxidative Damage, Proteolysis and Cell Function’

Abstract: Changes in the redox state are inevitably associated with protein oxidation. Severe oxidation is often leading to irreversible protein modification. Most of these proteins cannot be repaired and need to be degraded in order to maintain cellular homeostasis.

The proteasomal system (UPS) is the dominating system responsible for the degradation of such oxidatively modified proteins. In contrast to the normal protein turnover, such proteins are degraded in an ATP- and ubiquitin-independent matter. Lately, it was demonstrated that the autophagy-lysosomal system (ALS) contributes to the clearance of oxidized proteins, too.

Often chronic oxidative stress and aging are accompanied by a decline of the UPS and ALS. In a set of studies we could clearly demonstrate that the activity of the core 20S proteasome as well as the autophagosomal flux is declining during senescence in various postmitotic cell types. This is accompanied by the accumulation of oxidized, cross-linked proteins, often referred to as the aging pigment ‘lipofuscin’. Lipofuscin in turn has a number of metabolism-modulating effects, often enhancing the aging process itself or disturbing cellular function.

It is, therefore, of utmost interest to prevent the accumulation of oxidized proteins. The most promising aspect here is the stimulation of the proteolytic systems, which is possible as well for the UPS as for the ALS, in order to restore cellular function.


23.01.2023, 17:00 h, Room 417 Schiffbauergasse
Professor Claudia Grünauer-Kloevekorn from the Martin Luther University Halle, Germany will talk about ‘CTG18.1 repeat expansion and the reduction of TCF4 gene expression in corneal endothelial cells of German patients with Fuchs dystrophy’

Abstract: Fuchs’endothelial corneal dystrophy (FECD) is an age-related bilateral disorder affecting the cornea’s internal endo-thelial cell monolayer. This progressive disorder is the most frequent indication for corneal transplantation in the USA and affects nearly 4% of its population over the age of40 years. Microscopic collagenous excrescences of the endothelial basement membrane, so called guttae, are FECD’s clinical hallmark. Its disease course is marked by the growing density of guttae and gradual thickening of Descemet’s membrane, the basement membrane of the corneal endothelium. The endothelium’s loss of cell density, the loss of normal hexagonal cell patterns, and the deficient fluid pumping function are typical of premature senescence of the corneal endothelial layer in FECD patients.

20.03.2023, 17:00 h, Room 417 Schiffbauergasse
Professor Robin Ketteler from the MSB Medical School Berlin will talk about ‘Targeting Autophagy for Therapeutic Strategies in Pancreatic Cancer and Neurodegeneration’

Abstract: Autophagy is a cellular stress response that is tightly regulated by the controlled activity of AuTophaGy (ATG) genes. Defects in this pathway contribute to the development of disease, and strategies targeting individual ATGs are being developed for the treatment of cancer and neurodegeneration. We are particularly interested in the ATG4 family of cysteine proteases that catalyze the processing of the autophagy marker protein LC3 and explored the possibility to target ATG4 by small molecule compounds.

First, in order to understand the cellular function of the ATG4 proteases, we generated knockout cell lines by CRISPR/Cas9 genome editing and noted a severe defect in autophagosome formation. Furthermore, we observed that protein conjugates tagged with LC3 accumulate in ATG4 knockout cells, which constitutes a novel type of ubiquitin-like post-translational modification of proteins and may reflect a high degree of stress in these cells. These results demonstrate the essential function of ATG4s for basal autophagy.

Next, we have developed a 3-dimensional cell model for pancreatic ductal adenocarcinoma and tested ATG4 inhibitors with regards to cellular viability and cancer signaling pathways. In addition, we have performed large-scale small molecule screening to identify novel inhibitors and activators of ATG4, as well as general autophagy. For neuro-degenerative disorders, we have focused on the development of neuronal cell models derived from primary cells from patients with Parkinson’s disease (PD) and Beta-Propeller Associated Neurodegeneration (BPAN), a Parkinson-like disease that affects children. Using these models, we observed that the application of autophagy activators is beneficial for cellular health and function of patient-derived cells.

Overall, our results suggest that inhibitors of ATG4 have potential for strategies in pancreatic ductal adenocarcinoma, whereas activators of autophagy may be beneficial for treatment of neurodegenerative disorders such as PD and BPAN.

03.04.2023, 17:00 h, Room 317.1 Schiffbauergasse 14 and online (MS-Teams Link)
Dr. Filipovic from the Leibniz Institute for Analytical Sciences will talk about ‘Antiaging properties of protein persulfidation’

Abstract: In order to maintain life, nature actually uses a limited number of chemical reactions, one of which is sulfur-based chemistry, mainly exploited for the control of intracellular redox homeostasis and redox-based signaling. Hydrogen sulfide (H2S) is one of the simplest sulfur-containing molecules found in the cells and ever since the first report of its potential physiological role, there has been a burgeoning literature on the subject of H2S signaling. One of the main mechanisms through which this gasotransmitter conveys its message is protein persulfidation, i.e. transformation of protein thiols into persulfides (PSSH). Being “one sulfur away” from thiols, persulfides are not easy to monitor.

However, recent developments of persulfide labelling techniques have started unravelling the role of this modification in (patho)physiology. PSSH levels are important for the cellular defense against oxidative injury, albeit they decrease with aging, leaving proteins vulnerable to oxidative damage. By employing labelling developed in our group and combining it with proteomics, metabolomics and molecular biology, we aim to obtain high-resolution structural, functional, quantitative and spatio-temporal information on persulfidation dynamics and identify the protein targets whose persulfidation is implicated in ageing and age-related disease progression. We find that protein aggregation and proteasomal degradation are strongly controlled by PSSH and that genetic knockout of H2S producing enzyme results in Alzheimer’s disease like phenotype. These observations pave the way for the development of innovative therapeutic strategies that could delay aging and disease progression.