seminar talks:

Aging in the hematopoietic compartment (Kirschner)

Beyond clocks - the inner workings of DNA methylation dynamics (Chandra)

Dr. Kirschner’s lab deciphers how age‑driven alterations in hematopoietic stem cells fuel blood cancer risk. Her pioneering work combines single‑cell multiomics with population studies to build predictive tools for clonal hematopoiesis and explore senescence dynamics—advancing strategies to intercept age‑related disease

Dr. Chandra’s interdisciplinary research harnesses genomics, AI, and quantitative biology to unravel the molecular basis of epigenetic aging, senescence, and clonal mosaicism. His team probes how epigenetic clocks may be reset via partial reprogramming in blood, and applies AI-driven tools to stratify patient risk and rejuvenate aging phenotypes.

title: Shaping the genome with diet: how nutritional cues influence chromatin organization and function in a whole organism

Seminar talk by Dr. Daphne S. Cabianca from Helmholtz Zentrum, Munich.

Dr. Daphne S. Cabianca leads the Environment and Nuclear Organization group at Helmholtz Munich’s Institute of Functional Epigenetics. Her research focuses on how environmental cues—such as temperature or nutrient availability—reshape chromatin organization and gene expression. Using C. elegans as a model, her team combines CRISPR-based genome engineering, live imaging, and sequencing approaches to uncover how spatial chromatin dynamics contribute to cellular adaptation.

"Epigenetic determinants of genome stability for mammalian tissue", (project 1)

This project will elucidate epigenetic mechanisms promoting genome instability when tissue homeostasis declines with age and under physiological stress. We discovered elevated G– quadruplex (G4) DNA secondary structure formation in mutated highly transcribed gene regulatory regions of cancer, suggesting dysregulated G4s as promoter of genome instability. We have and continue to gather evidence that dysregulated G4s emerge before cancer development in physiologically aged murine tissues and rapidly aged murine and human models. We hypothesize here that dysregulated G4 secondary structure formation may promote genome instability and heterostasis in aged and stress-induced rodent tissues. By exploiting our newly developed multiomics technology to jointly map epigenetically linked DNA breakage landscapes, beyond association, we will identify epigenetic mechanisms that critically drive persistent and/or elevated DNA breakage. To identify epigenetic regulators that promote an increase in epigenetically linked DNA breakage in tissues of our rodent models, we will use computational predictions and experimental associations of our multiomics data with existing data sets. We will use proximity ligation proteomics of tissue-derived nuclei to directly link regulatory factors to epigenetically linked DNA breakage and validate these findings by genetic loss-of-function in C. elegans. 

title: tba

Seminar talk by Dr. Sylvie Noordermeer from Leiden University Medical Center.

DNA double-strand breaks (DSBs) are one of the most cytotoxic lesions and can lead to diseases such as cancer when repaired erroneously or left unrepaired. Our cells are equipped with several mechanisms to repair these DSBs, showing differences in efficiency and fidelity. Using a variety of systemic approaches (large scale CRISPR and yeast-two-hybrid screens, proteomics) and dedicated molecular biology approaches to assess genomic stability and break repair we aim to understand how the cell regulates its DSB repair and how the repair mechanisms communicate with other cellular processes such as replication.

We aim to explore the causes and consequences of deregulated DNA repair to explain important phenotypes observed in our novel human genome instability syndromes. Importantly, these insights will serve as a blueprint to understand the intricate relationship between the DDR, protein homeostasis and neurodegeneration. 

title: tba

Seminar talk by Dr. Puck Knipscheer from Hubrecht Institute.

MECHANISM AND CONSEQUENCES OF SLX4IP- AND ERCC1-XPF-DEPENDENT TELOMERE DYSFUNCTION (project 6)

lab: Stephanie Panier

Somatic cells have finite replicative lifespans because telomeres undergo progressive shortening after DNA replication, which can lead to genome instability and induce senescence. Telomere dysfunction has profound physiological consequences and promotes the accelerated development of many age-associated pathologies such as tumorigenesis and kidney disease. We have previously described the adapter protein SLX4IP as an important regulator of recombination-based Alternative Lengthening of Telomeres (ALT), which is a telomerase-independent telomere maintenance mechanism. Intriguingly, SLX4IP interacts with the heterodimeric structure-specific endonuclease ERCC1-XPF, which cleaves the 3′ flaps of DNA intermediates that occur during several DNA repair pathways and also as a consequence of telomere maintenance. The physiological importance of ERCC1-XPF is underscored by the fact that inactivating mutations in XPF are associated with several genome instability syndromes. In addition, ERCC1-XPF is essential for kidney homeostasis and its loss leads to glomerular aging and renal fibrosis. To date, it remains entirely unclear why and how SLX4IP interacts with ERCC1-XPF and how this interaction relates to the cellular and physiological functions of this endonuclease. The objectives of this research proposal are, thus, to understand how SLX4IP regulates ERCC1-XPF function to ensure telomere stability and to elucidate the physiological consequences of a dysfunctional SLX4IP-ERCC1-XPF module. Specifically, we propose to characterize the molecular relationship of SLX4IP and ERCC1-XPF, to investigate how SLX4IP modulates ERCC1-XPF telomere functions, and to understand the consequences of a dysfunctional SLX4IP-ERCC1-XPF module on general genome maintenance and on organ homeostasis using mouse kidney fibrosis as model system.

A damage driven transcription stress on aging and the effect of calorie restriction, project 7

Joris investigates how chronic genome instability disrupts tissue homeostasis, focusing on transcriptional stress and its systemic impacts during aging. Using progeroid DNA-repair-deficient mouse models, he revealed that transcriptional stalling induces metabolic dysfunction and accelerates tissue degeneration, including neurodegeneration. His groundbreaking discovery of dietary restriction as a therapy shows it mitigates DNA damage, reprograms metabolism, and significantly extends lifespan, offering a translational approach to aging-related diseases.

title: tba

Seminar talk by Dr. Charléne Boumendil from CNRS- Institute of Human Genetics, UMR 9002.