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.

12.06.2023, 17:00 h, Room 717 Schiffbauergasse 14 and online (MS-Teams Link)
Søren Tvorup Christensen from the University of Copenhagen will talk about ‘Deciphering TGFB/BMP signaling by primary ciliary in health and disease’

Abstract: Primary cilia are antenna-like organelles that project from centrosomes at the cell surface and play key roles in signaling, in turn controlling development and function of most tissues and organs in our body. Mutations impairing cilia lead to >35 severe human diseases (ciliopathies), collectively affecting 1 in 400 people, with pleiotropic, overlapping phenotypes ranging from respiratory disease, blindness and cancer to kidney, heart and brain disorders. The etiology of many ciliopathies is, however, unclear, and rationally designed and effective therapies are lacking. Moreover, molecular and mechanistic insights into the dynamics of cilia composition, structure and function in different cell- and developmental contexts, and the implications thereof, remain scarce. This represents a major challenge for understanding the fundamental biology of cells and development, as well as for developing diagnostics and precision medicine. The overarching objective of our lab is to decode the diversity, complexity, and interplay of cilia functions and elucidate how defective cilia cause disease. Our efforts are organized around four major themes, which investigate cilia function at different organizational scales – from the molecular-nanometer scale, to the cellular level, to tissues and organism organization and in patients. In this seminar talk, I will give examples of how primary cilia balance the output of cellular TGFB/BMP signaling, and how defects in this system underlie congenital heart disease and primary microcephaly.

04.07.2023, 17:00 h, Room 417 Schiffbauergasse 14
Ann E. Ehrenhofer-Murray from the Institut für Biologie, Humboldt-Universität zu Berlin will talk about ‘Queuosine modification in tRNAs: Novel detection methods and functional characterization’

Abstract: In bacteria and eukaryotes, the wobble position of tRNAs with a GUN anticodon is modified to the 7-deaza-guanosine derivative queuosine (Q34). Q34 modification stimulates Dnmt2 -dependent C38 methylation (m5C38) in the tRNAAsp anticodon loop in Schizosaccharomyces pombe and other eukaryotes. Q modification ensures that the respective tRNAs can decode codons that differ at the Wobble position, and it thus equilibrates the genome-wide translation of synonymous Q codons. Furthermore, Q suppresses translation errors.

Interestingly, the original source of the queuine nucleobase in eukaryotes is bacterial, since Q is synthesized by eubacteria and salvaged by eukaryotes for incorporation into tRNA. We found that the utilization of the nucleotide Q as a source of queuine requires hydrolysis of the N-glycosidic bond by the enzyme Queuosine nucleoside glycosylase (Qng1) in Schizosaccharomyces pombe.

Current methods for the detection of Q modification rely on mass spectrometry or boronate-containing polyacrylamide gels combined with Northern blotting. However, neither technique is adequate to identify novel Q-modified RNAs or to verify Q modification of long RNAs. We have established a novel method of metabolic labelling of Q-modified RNAs which we employed to label and isolate such RNAs for high-throughput sequencing (HTS). Furthermore, we have developed a method for Q mapping at single-nucleotide resolution based on mismatch incorporation by reverse transcription combined with HTS. Thirdly, we have adapted direct RNA sequencing using nanopore technology to detect queuosine and its precursors preQ1 and preQo. These methods provide orthogonal techniques for the detection of Q modification that can be employed to any RNA species.

10.07.2023, 17:00 h, Room 417 Schiffbauergasse 14
Dr. rer. nat. Joachim Michael Matz from the Molecular Parasitology Group will talk about ‘The bottomless pit: functions of the digestive vacuole in malaria parasite physiology and antimalarial drug uptake’

Abstract: In 2021, more than 600,000 people died of malaria, with most deaths occurring in sub-Saharan Africa in children under five. Despite rigorous control programs, malaria eradication remains one of the most testing medical challenges of the 21st century. Owing to the rapid emergence and spread of drug resistance, innovative intervention strategies are urgently needed and strictly depend on our improved understanding of the complex biology underlying this devastating disease. Malaria is caused by Plasmodium parasites, which replicate within human erythrocytes. During intraerythrocytic growth, the parasite takes up and digests host cell hemoglobin in an acidified vacuole. Several antimalarials interfere with biochemical pathways in this vacuole leading to parasite death. It was long believed that accumulation of these drugs is a mere function of the pH gradient between parasite cytosol and the vacuolar lumen. By targeting the multimeric proton pump powering this gradient, we identify distinct functions of this protein complex in physiology and maintenance of the digestive vacuole. Contrary to current belief, we find that severe dissipation of the proton gradient, has only limited impact on drug uptake and no effect on drug susceptibility, overturning an over 50-year-old dogma in antimalarial chemotherapy.

18.09.2023, 17:00 h, Room 417 Schiffbauergasse 14
Prof. Dr. Christoph Taxis from the Health and Medical University Erfurt will talk about ‘Optogenetic control of protein degradation in eukaryotic cells – development and applications‘

Abstract: Optogenetic control of protein activity is a versatile technique to gain control over cellular behavior. Best known is the application of optogenetics in neurons to study behavior in complex organisms. Natural photoreceptors from plants and microorganisms are coupled with diverse cellular effectors to create an optogenetic tool and control a specific cellular activity by light. A general approach to control protein activity is the regulation of protein abundance, e.g. by influencing protein stability. Photoreceptor-based control of protein stability relies on the light-controlled release of degradation-inducing sequences (degron) that trigger protein degradation by the ubiquitin-proteasome system in eukaryotes. Development of the photosensitive degradation (psd) module in budding yeast used the photoreceptor domain of the plant protein phototropin and the ornithine decarboxylase degron from mouse. After proof of concept the psd module was improved by optimization of the photoreceptor part as well as embedding the psd module in a light-controlled regulatory network. The outcome was a toolbox of synergistic optogenetic tools that control protein abundance. These optogenetic modules were applied to biotechnology and basic research in the ubiquitin-proteasome system and the investigation of protein quality control mechanisms. The latter are essential for degradation of misfolded, disfunctional or supernumerous proteins. An important step in protein degradation is the recognition of defective proteins by protein quality control components. The selection for degradation often relies on the recognition of short, linear peptide motifs called degrons. Optogenetics provides the opportunity to investigate in detail protein quality control mechanisms and characterize degrons of strong and weak activity. We used this approach to identify stabilizing and destabilizing sequences at the C-terminus of proteins in budding yeast. The latter are surprisingly frequent and induce degradation via the cullin-RING E3 complex using Das1 as adaptor protein. Interestingly, natural proteins in yeast have evolved to contain stable C-terminal sequences that are not targeted by protein quality control pathways. Overall, application of optogenetics is not restricted to the nervous system but is a versatile approach that is applicable in many areas of biotechnology or basic research.

09.10.2023, 17:00 h, Room 417, Schiffbauergasse 14
Dr. Sarah Starosta from the Cold Spring Harbor Laboratory will talk about A neuro-immune circuit mediates cancer cachexia-associated apathy

Abstract: Cachexia, a severe wasting syndrome associated with multiple inflammatory conditions, precipitates multi-organ dysfunction and is often fatal. Patients with cachexia frequently experience clinical depression, extreme fatigue, and apathy; however, the underlying biological mechanisms of these symptoms and their relationship to cachexia remain unclear. In a mouse cancer model, we demonstrate that cachexia triggers apathy-like symptoms through a cytokine-sensing brainstem-to-basal ganglia circuit. This circuit detects elevations in IL-6, an inflammatory cytokine, at cachexia onset, and translates it into decreased mesolimbic dopamine, thereby increasing behavioral effort-sensitivity. These apathy-like symptoms were alleviated through three approaches: administering an anti-IL6 antibody treatment, ablating cytokine sensing in the area postrema or optogenetically stimulating mesolimbic dopamine neurons. Our findings uncover a central neural circuit that senses inflammation and orchestrates behavioral changes, providing mechanistic insights into the connection between chronic inflammation and depressive symptoms.

Dr. Manfred Gossen from the Helmholtz-Zentrum Hereon Potsdam will talk about „From stable (sometimes …) to transient genetic engineering“

Dr. Katarzyna Polak-Krasna from the Helmholtz-Zentrum Hereon Potsdam will talk about "Applications of Active Polymers in Active Cardiac Implants”