Polášek-Sedláčková Hana, Mgr., Ph.D.

Extension: +420 541-517- 292

What was your research journey before establishing a new research group at the Institute of Biophysics?

From an early age, I have always been interested in fundamental cellular processes, especially how the cell regulates genome duplication to achieve the most accurate copy of genetic information. I started my research path in 2010 as a grammar school student by joining the laboratory of Dr. Lumir Krejci at Masaryk University. In his laboratory, I continued as a bachelor's and master's student and contributed to studies aimed at understanding the biochemical activity of RecQ helicases and their role in processing various DNA intermediates formed during DNA replication and repair (Sedlackova H et al., DNA Repair, 2015; Di Marco S et. al, Mol Cell, 2017). After finishing my master's studies, I was selected for the prestigious Copenhagen Bioscience Ph.D. program. With this scholarship, as a Ph.D. student, I joined the laboratory of Prof. Jiri Lukas at the NNF Center for Protein Research at the University of Copenhagen. During my Ph.D., I studied the basics of human DNA replication and contributed to the discovery of new roles of dormant MCMs and metabolic inputs in the protection of genome integrity through replisome speed control (Sedlackova H et al. Nature 2020; Somyajit K, Gupta R, Sedlackova H et al. Science 2017). After successfully defending my Ph.D. thesis in 2020, I continued in the laboratory of Prof. Jiri Lukas as a postdoctoral fellow studying the plasticity of DNA replication machinery in living cells. Our recent study (Polasek-Sedlackova H, et al. Nature Communications, 2022), initiated during my postdoc and completed in my independent laboratory, clarified long-standing challenges in imaging DNA replication forks in living cells.

What are you currently working on? Why do you find your project/work fascinating?

In 2021, I was selected for the prestigious Czech Science Foundation: Junior Star supporting the best scientists in their early-stage careers. With this starting grant, I established a new research group in the Department of Cell Biology and Epigenetics at the Institute of Biophysics, CAS. The research program of my group bridges basic DNA replication research with cancer research and the developmental biology field aiming to understand how DNA replication origins are regulated in mammalian cells to achieve high fidelity in copying genomes.

Science is what I literally live for, and even after years of research, I really enjoy it. What fascinates me are the true wonders of science under the microscope - I fell in love with cell biology during my Ph.D. studies and I will probably never get tired of watching the basic processes of life directly in the cell. As a group leader, I really enjoy working with many talented students and researchers, discussing research projects, and of course the moment of surprise when we together discover something completely unexpected.

What do you do when you are not in the lab?

In the summer, I like to spend my free time on a bike or inline skates in the beautiful region of South Moravia. In the winter, I love to spend long winter evenings in Danish 'hygge' style watching movies or reading books, a good fantasy or Nordic crime novels are always the best options.

Read more about the career path & research of Dr. Hana Polasek-Sedlackova here or here.

Curriculum vitae

PERSONAL INFORMATION

Mgr. Hana Polasek-Sedlackova, Ph.D.
ORCID ID: 0000-0001-8234-6176
Nationality: Czech

CURRENT ADDRESS

Department of Cell Biology & Epigenetics
Institute of Biophysics
Czech Academy of Sciences
Kralovopolska 135
612 00 Brno
Czech Republic

CURRENT POSITION

group leader at the Department of Cell Biology and Epigenetics, Institute of Biophysics, Czech Academy of Sciences

EDUCATION AND ACADEMIC QUALIFICATIONS

2016–2020: PhD in Molecular Mechanisms of Disease
Research topic: Discovery of new roles of dormant MCMs and metabolic inputs in the protection of genome integrity through replisome speed control.
Supervisor: Prof. Jiri Lukas
Co-supervisors: Dr. Kumar Somyajit, Ass. Prof. Julien Duxin, Prof. Anne Grapin-Botton, Prof. Julian Blow
Research laboratory: Laboratory of Chromosome Stability and Dynamics, Protein Signaling Program at Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
PhD program: Novo Nordisk Foundation Copenhagen Bioscience PhD Program; Molecular Mechanisms of Disease PhD Program at University of Copenhagen
2014–2016: MSc in Biochemistry of Genomes and Proteomes
Supervisor of MSc research project: Dr. Lumir Krejci
Research laboratory: Laboratory of Recombination and DNA repair, Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
2011–2014: BSc in Biochemistry
Supervisor of BSc research project: Dr. Lumir Krejci
Research laboratory: Laboratory of Recombination and DNA repair, Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic

RESEARCH EXPERIENCE

2022–present: group leader at the Department of Cell Biology and Epigenetics, Institute of Biophysics, Czech Academy of Sciences v. v. i., Czech Republic
Research topic: Deciphering Origins of DNA replication in genome integrity
2020–2022: Postdoctoral Fellow in the Laboratory of Chromosome Stability and Dynamics, Protein Signaling Program at Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
Supervisor: Prof. Jiri Lukas
Research topic: Exploring biochemical properties of parental and nascent MCMs determining their distinct function in DNA replication program.
2016-2020: PhD student in the Laboratory of Chromosome Stability and Dynamics, Protein Signaling Program at Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
Supervisor: Prof. Jiri Lukas
Research topic: Discovery of a novel role of surplus licensed MCMs in modulating physiological dynamics of replication fork progression. Discovery of redox-controlled adjustment of DNA replication speed as the first-in-line molecular surveillance of replicating genomes.
2010–2016: MSc, BSc and Grammar School student in the Laboratory of Recombination and DNA repair, Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Supervisor: Dr. Lumir Krejci
Research topic: Characterization of RecQ helicases and their roles in resolution of DNA intermediates arising during DNA replication and repair.
2014: Scientific internship in the Laboratory of Prof. Ian Hickson at Center for Chromosome Stability, University of Copenhagen, Denmark
Supervisor: Prof. Ian Hickson
Research topic: Identification of the RECQ4 role in DNA replication origin firing through its interaction with MCM10 firing component in DT40 avian cells.

ACADEMIC AWARDS

2023: European Research Area (ERA) individual fellowship, Czech Republic
2022: Czech Science Foundation: Junior Star starting grant, Czech Republic
2021: Nomination for the NNF Center for Protein Research Technology Award, Copenhagen, Denmark
2018: Best poster award at EMBO workshop: DNA replication, chromosome segregation and fate decisions, Kyllini, Greece
2017: Best poster award at Fusion conference: 2nd DNA Replication as a source of DNA damage conference, Rome, Italy
2016: Award of the Minister of Education, Youth and Sports in Czech Republic for outstanding students and graduates of the study program and for extraordinary deeds of students, Prague, Czech Republic
2016: NNF Copenhagen Bioscience PhD Program, PhD scholarship, Copenhagen, Denmark
2016: Award of the Dean of the Faculty of Science at Masaryk University for publishing excellent results of own research, Brno, Czech Republic
2015: The Undergraduate Award, gold medal in Life Sciences, Dublin, Ireland
2014: Award of the Dean of the Faculty of Science at Masaryk University for the best student scientific work presented on student conference, Brno, Czech Republic
2013: Price of Cori Spouses for the best presentation, XIII. Meeting of Young Chemists and Biochemists, Zdar nad Sazavou, Czech Republic
2013: GE Foundation Scholar Leader, international scholarship for academic achievements and scientific results, Budapest, Hungary
2011: Ceska Hlavicka in category GENUS, Prague, Czech Republic

ACADEMIC ACTIVITIES

Invited Talks and Oral Presentations:

2022: Invited talk at Copenhagen Bioscience Snapshot seminar series, Copenhagen, Denmark
2022: Invited talk at Functional Organization of the Cell Nucleus Symposium, Charles University, Prague, Czech Republic
2022: Selected for oral presentation at UK DNA replication meeting 2022, Birmingham, UK
2021: Invited talk in Chromatin Dynamics & DNA Damage Response journal club webinar series, organized by PhD students of aDDRess, MSCA-ITN network
2021: Invited talk at Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic
2019: Selected for oral presentation at Cold Spring Harbor: Eukaryotic DNA replication meeting, New York, USA
2018: Selected for oral presentation at NNF Conference on Protein Signaling, Hillerød, Denmark
2015: Invited talk at The Undergraduate Awards Global Summit, Dublin, Ireland
2015: Selected for oral presentation at 7th EMBO YIP Sectoral Meeting Genome Integrity Forum, Strasbourg, France
2013: Selected for oral presentation at XIII. Meeting of Young Chemists and Biochemists, Zdar nad Sazavou, Czech Republic

Organization of International Meetings:

2018:Copenhagen Bioscience Symposium: The Complexity of Ageing, University of Copenhagen, Denmark

ACADEMIC FUNDING

2023-2026: ERA individual fellowship, funded by European Research Executive Agency, Grant number: 101090292, Project title: Regulation of DNA replication origins during normal development and tumorigenesis
2022-2026: GACR: Junior Star, starting grant funded by Czech Science Foundation, Grant number: 22-20303M, Program title: Deciphering Origins of DNA replication in genome integrity
2016-2020: NNF Copenhagen Bioscience PhD Program, fully funded PhD program by Novo Nordisk Foundation, Grant number: NNF16CC0020906, Project title: The mechanism of replication fork progression through dormant origins
2015: Program of the Rector of Masaryk University, support of student’s projects at Masaryk University, Category C: support for excellent diploma thesis, Grant number: MUNI/C/1488/2014, Project title: The role of RECQ4 helicase on proper chromosome segregation in mitosis

TEACHING ACTIVITIES

2022-present: Supervisor of Anoop Kumar Yadav (Ph.D. student in the Molecular and Cell Biology and Genetics Program, Masaryk University, JCMM scholarship for foreign students)
2022-present: Supervisor of Ayushi Tomar (Master‘s student in the Molecular and Cell Biology Program, Masaryk University)
2022-present: Supervisor of Anna Hrdlickova (Bachelor‘s student in the Experimental and Molecular Biology Program, Masaryk University)
2014–2016: Supervisor of Barbora Cechova (grammar school student, Ceska hlaviska 2016, 4th place at the Intel ISEF international competition in the USA) in the laboratory of Dr. Lumir Krejci
2013–2016: Lecturer in BIOSKOP, Scientific and Learning Center of Masaryk University

SCIENTIFIC FOCUS AREA

My research is focused to decipher fundamental cellular processes, especially how the cell regulates the process of genome duplication to achieve the most accurate copy of genetic information and its transmission to the next cell generations. Understanding these fundamental processes is key to cancer treatment because up to two-thirds of all cancers are caused by the accumulation of errors during genome duplication. During my Ph.D. studies in the laboratory of prof. Jiri Lukas, I studied the basics of human DNA replication and contributed to the discovery of new roles of dormant MCMs and metabolic inputs in the protection of genome integrity through replisome speed control (Sedlackova H, et al. Nature 2020; Somyajit K, Gupta R, Sedlackova H, et al. Science 2017). In the first major work of my Ph.D., we identified a novel MCM homeostasis pathway that ensures precise replication origin assembly and dynamics of individual replication forks. Specifically, we have shown that error-free genome duplication depends on the recycling and biogenesis of MCMs, resulting in two different protein forms — parental and nascent MCMs. While parental MCMs are preferentially converted to active CMG helicases, nascent MCMs remain largely inactive but are critical to set up the physiological pace of replication fork progression essential to protect genome integrity. In addition, this work provided new functional insights into the long-debated MCM paradox. In the second collaborative work, we found that DNA replication is tightly aligned with oscillations in metabolic pathways. Specifically, we identified and functionally characterized a novel signaling cascade that adjusts replication fork velocity with fluctuations of metabolic nucleotide biosynthesis and serves as first-in-line molecular surveillance of replicating genomes. Taken together, these two studies identified previously concealed mechanisms of replication fork speed modulation, which are essential to mitigate genome instability promoting the development of diseases, including cancer. In our recent study (Polasek-Sedlackova H, et al. Nature Communications, 2022), we explained the enigmatic second part of the MCM paradox (inability to see replicative helicase in living cells) by visualizing the MCM scaffold of active replisomes at DNA replication sites inside cells. This study opens new avenues to investigate replication dynamics and the emergence of replication stress (a hallmark of cancer) directly in living cells. The research program of my group at the Institute of Biophysics bridges basic DNA replication research with cancer research and the developmental biology field. The research projects focus on understanding how DNA replication origins are regulated in mammalian cells to achieve high fidelity in copying genomes. By combining physiologically relevant cellular models (mouse and human embryonic stem cells) with state-of-the-art CRISPR-Cas9 genome editing, quantitative cell biology, genomics, and proteomics approaches, we study the regulation of genome duplication during normal mammalian development in specialized tissues such as cardiomyocytes and oncogene-induced malignant transformation. Our research program has great potential to illuminate how malfunctions of molecular pathways required for error-free DNA replication affect genomic fitness in ensuing generations of dividing cells and reveal new drug targets and therapeutic strategies for cancer treatment.

LIST OF PUBLICATIONS

Research articles:

Polasek-Sedlackova H, Miller TCR, Krejci J, Rask MB, Lukas J. (2022) Solving the MCM paradox by visualizing the scaffold of CMG helicase at active replisomes. Nature Communications 13(1):6090
Sedlackova H, Rask MB, Gupta R, Choudhary C, Somyajit K, Lukas J. (2020) Equilibrium between nascent and parental MCM proteins protects replicating genomes. Nature 587: 297-302
Ochs F, Karemore G, Miron E, Brown J, Sedlackova H, Rask MB, Lampe M, Buckle V, Schermelleh L, Lukas J, Lukas C. (2019) Stabilization of chromatin topology safeguards genome integrity. Nature 574: 571-574
Somyajit K, Gupta R, Sedlackova H, Neelsen KJ, Ochs F, Rask MB, Choudhary C, Lukas J. (2017) Redox-sensitive alteration of replisome architecture safeguards genome integrity. Science 358: 797-802
Di Marco S, Hasanova Z, Kanagaraj R, Chappidi N, Altmannova V, Menon S, Sedlackova H, Langhoff J, Surendranath K, Huhn D, Bhowmick R, Marini V, Ferrari S, Hickson ID, Krejci L, Janscak P. (2017) RECQ5 helicase cooperates with MUS81 endonuclease in processing stalled replication forks at common fragile sites during mitosis. Mol Cell 66: 658-671
Kliszczak M, Sedlackova H, Pitchai GP, Streicher WW, Krejci L, Hickson ID. (2015) Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells. Oncotarget 6: 40464-40479
Sedlackova H, Cechova B, Mlcouskova J, Krejci L. (2015) RECQ4 selectively recognizes Holliday junctions. DNA Repair (Amst) 30: 80-89
Chavdarova M, Marini V, Sisakova A, Sedlackova H, Vigasova D, Brill SJ, Lisby M, Krejci L. (2015) Srs2 promotes MUS81-MMS4-mediated resolution of recombination intermediates. Nucleic Acids Res 43: 3626-3642

Review articles:

Spies J, Polasek-Sedlackova H, Lukas J, Somyajit K. (2021) Homologous Recombination as a Fundamental Genome Surveillance Mechanism during DNA Replication. Genes 12(12):1960