Institute of Molecular Genetics of the Czech Academy of Sciences
The main research of our group is focused on ADP-ribosyl transferases; a class of DNA repair enzymes that detect DNA single-strand breaks (SSBs) and signal their presence by catalysing the rapid synthesis of mono(ADP-ribose) and poly(ADP-ribose) and hydrolases; enzymes that catalyse the removal of specific ADP-ribosyl modifications from proteins…
Supervisor
Hana Hanzlíková
Project description
ADP-ribosylation is a vital post-translational modification involved in DNA repair, chromatin remodelling, transcription regulation, and cell death. Despite advancements in understanding Poly-ADP-Ribose Polymerases (PARPs), particularly PARP1 and PARP2, their specific roles in these processes, especially in the brain, remain incompletely understood. Persistent or aberrant ADP-ribosylation, triggered by DNA damage or transcriptional stress, can disrupt neuronal function and transcriptional regulation, contributing to neurological disorders.
This project focuses on unravelling the molecular mechanisms of histone serine mono-ADP-ribosylation, with an emphasis on its regulation by PARP2 and its relevance to neurological diseases. We hypothesize that histone serine ADP-ribosylation modulates chromatin structure and gene expression—processes crucial for neuronal development, function, and responses to stress. Dysregulation of these mechanisms may promote neurodegeneration.
To address this, we utilize advanced experimental models, including patient-derived iPSCs, 3D cerebral organoids, and knockout mice, alongside state-of-the-art molecular tools such as CUT&RUN, mass spectrometry, single-cell RNA sequencing, and spatial transcriptomics. These approaches enable a comprehensive investigation of PARP2-driven histone ADP-ribosylation and its impact on brain-specific regulatory networks under normal and stressed conditions.
By providing new insights into how histone serine ADP-ribosylation influences chromatin dynamics and gene regulation in neurons, this research aims to uncover novel biomarkers and therapeutic strategies for neurological diseases.
Candidate profile
We are seeking a highly motivated candidate with a strong foundation in biochemistry, molecular biology, and cell biology. Applicants must hold a relevant Master’s degree and have a keen interest in our research area. Experience with advanced techniques such as mass spectrometry, single-cell RNA sequencing, or spatial transcriptomics is an advantage. The ideal candidate should demonstrate excellent teamwork skills and a collaborative mindset, as the position involves close interaction with other lab members and international partners. A proactive attitude and a willingness to engage with diverse experimental models and cutting-edge technologies are essential.
We provide an enthusiastic and inspiring research environment, supported by state-of-the-art facilities, at an attractive working location in Prague, Czech Republic. Our research is internationally recognized and driven by collaborative efforts. The lab works closely with leading research groups, including the Caldecott group at the University of Sussex, UK, and the Rottenberg and the Hanzlikova group at the University of Bern, Switzerland.
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In our laboratory we study processes and mechanisms, which govern epithelial morphogenesis and homeostasis, and how their deregulation can lead to developmental defects and cancer…
Supervisor
Zuzana Sumbalová Koledová
Project description
Lactation is a critical physiological process requiring precise coordination of cellular functions, including DNA replication, transcription, and the DNA damage response, to support milk production. This PhD project aims to unravel the molecular mechanisms underlying these processes in lactating mammary epithelial cells. Using a cutting-edge lactation organoid model developed in our laboratory, combined with in vivo mouse models, the student will explore how DNA replication and transcription and DNA damage response regulate differentiation of luminal cells to milk-secreting alveolar cells. Advanced imaging techniques, transcriptomics, and molecular biology tools will be employed to investigate these pathways in detail. The findings will provide new insights into the fundamental biology of lactation and may identify novel targets for addressing lactation-related disorders, contributing to improved maternal and neonatal health.
Candidate profile
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Supervisor
Zuzana Sumbalová Koledová
Project description
This project focuses on the development of innovative human mammary organoids as an advanced in vitro model to investigate breast morphogenesis, a fundamental process in mammary gland development and a critical factor in breast cancer progression. The aims are to optimize protocols for generating human mammary organoids that faithfully recapitulate key aspects of mammary gland morphogenesis, including branching morphogenesis, epithelial differentiation, and hormonal responsiveness. Using advanced imaging methodologies such as confocal microscopy and live-cell imaging, the structural organization and dynamic behavior of these organoids will be characterized in unprecedented detail. Molecular profiling techniques, including transcriptomics and proteomics, will provide insights into the regulatory networks and signaling pathways governing mammary organoid development.
By integrating these approaches, the study seeks to address critical gaps in our understanding of the molecular mechanisms underlying breast development and disease. The resulting human mammary organoids will serve as a robust platform for studying breast cancer initiation and progression, offering a more physiologically relevant alternative to traditional models. Ultimately, this work has the potential to drive the development of more effective therapeutic strategies for breast cancer, a disease that remains a leading cause of morbidity and mortality worldwide.
Candidate profile
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