|Jana Dobrovolná, Ph.D.|
|Address:||Institute of Molecular Genetics of the ASCR, v. v. i.|
142 20 Prague 4, Czech Republic
|+420 241 063 127|
+420 241 063 112
|Fax:||+420 241 062 289|
|Born:||December 31, 1976; Prague, Czech Republic|
|2002 - 2008||Ph.D. studies at the Faculty of Science, Charles University in Prague, Czech Republic
Thesis: Regulation of promyelocytic leukemia (PML) gene expression.
Supervisor: Zdenek Hodny, MD, PhD and Prof. Pavel Hozak, PhD
|1995 - 2001||Master’s degree in Biology at Charles University in Prague, Faculty of Natural Sciences, Czech Republic
Thesis: The study of hormone induced changes in G-protein content in membrane microdomains
Supervisor: Doc. Petr Svoboda, PhD
|01/2020 – present||Research fellow at the Laboratory of Cancer Cell Biology, Institute of Molecular Genetics, v.v.i., Academy of Sciences of the Czech Republic, Czech Republic. |
Head of Department: Libor Macůrek, PhD
Head of the project: Pavel Janščák, PhD
|02/2013 – 11/2019||Postdoctoral research fellow at the Department of Genome Integrity, Institute of Molecular Genetics, v.v.i., Academy of Sciences of the Czech Republic, Czech Republic. |
Head of Department: Prof. Jiří Bártek, MD, DSc
Head of the project: Pavel Janščák, PhD
|06/2008 – 12/2011||Postdoctoral research fellow position at Hospital for Special Surgery, New York, N.Y., USA. |
Head of Laboratory: Inez Rogatsky, PhD
|07/2002 – 12/2007||Research investigator at the Institute of Experimental Medicine and the Institute of Molecular Genetics, Department of Biology of the Cell Nucleus, Academy of Sciences of the Czech Republic. |
Head of Department: Prof. Pavel Hozak, PhD
|1996– 2001||Young investigator at the Institute of Physiology, Academy of Science of the Czech Republic. |
Head of Department: Doc. Petr Svoboda, PhD
Role of R-loops in onset of genomic instability and counteracting molecular mechanisms
Cancer is one of the main causes of death; world-wide it accounts for 13 % of the total number of deaths. The vast majority of human cancers are linked to genome instability, a hallmark of the transition of a normal cell to a pre-cancerous cell. The pre-cancerous cells are still benign, but because of an acquired selective advantage they have an increased potential to be transformed to fully malignant cells. Activated oncogenes that can drive such a transformation were recently shown to induce extensive replication stress, e.g. stalling or collapse of replication forks, preferentially at specific genomic regions called common fragile sites (CFSs). Replication stress can result from collisions between replication machinery and oncoming transcription complexes, which can lead to the formation of highly genotoxic RNA:DNA hybrids referred to as R-loops. A link between the breakage of CFSs and the formation of R-loops as a consequence of replication/transcription encounters has recently been established. R-loops are composed of the nascent RNA annealed to the DNA template strand and unpaired complementary DNA strand that is vulnerable to breakage. Despite of growing evidence that unscheduled formation and stabilization of R-loops in eukaryotic cells challenges genomic integrity, the mechanisms involved in the resolution of these structures remain poorly understood.
The goal of our work is to advance understanding of the molecular mechanisms underlying R-loop formation, prevention and resolution and to explore the possible role of these structures in oncogene-induced DNA damage. Specifically, we aim to identify proteins that bind to R-loop structures under conditions of replication stress and to establish the functional significance of these proteins in the resolution of transcription/replication collisions and in suppression of transcription-associated genomic instability. Further, we aim to identify on genome-wide scale the loci that are prone to R-loop formation upon oncogene-induced replication stress.
Current Ph.D. students
Barbora Boleslavská (supervisors: Jana Dobrovolná, Pavel Janščák)
Zuzana Naščáková (supervisors: Jana Dobrovolná, Pavel Janščák)
Anna Oravetzová (supervisors: Jana Dobrovolná, Pavel Janščák)
Roman Straňanek (supervisors: Jana Dobrovolná, Pavel Janščák)
Jana Fryzelková (MSc student, supervisors: Jana Dobrovolná, Václav Urban) defence at 2018
Edita Křížová (PhD student)
Positions for undergraduate students (to achieve Bc. or Mgr.) and for PhD students are available.
Feel free to contact Jana Dobrovolna email@example.com for detail information any time.
Maintenance of genome stability, oncogene-induced replication stress, G-quadruplex structures, R-loops, transcription-replication interference
DNA damage is a frequent event in the life of a cell. Failure to repair DNA damage can lead to cell death, while inaccurate DNA repair can give rise to genomic instability, which promotes the onset of cancer in mammals. Research in our laboratory focuses on understanding various DNA repair mechanisms operative in mammalian cells. Our main aim is to define the exact DNA transactions that mediate the resolution of conflicts between transcription and replication machineries, a major source of genomic instability driving cancer development. Recently, we obtained a highly prestigious grant GAČR-EXPRO in collaboration with Dr. Lumír Krejčí from the Masaryk University to study the molecular mechanisms underlying the formation and resolution of RNA:DNA hybrids (R-loops), highly genotoxic structures that can arise as a consequence of transcription-replication conflicts.
The successful candidate will be working on the projects headed by Dr. Pavel Janscak and Dr. Jana Dobrovolna.
Candidate’s profile (requirements):
PhD or MSc degree in biochemistry or molecular/cellular biology, good English, independent thinking, strong interest in basic research and experimental work. Background in DNA damage response, cell cycle regulation or mechanisms regulating DNA replication and transcription is an advantage.
Institute of Molecular Genetics is located in the new, modern building with the state-of-art equipment. Laboratory of Cancer Cell Biology has a long-standing interest in mechanisms of genome integrity maintenance and applies a broad spectrum of approaches. The group is publishing in high profile journals and has good funding. The successful candidate can take a short-term internships in collaborating laboratory at the Institute of Molecular Cancer Research, University of Zurich, Switzerland. Work in young and motivated collective. Competitive salary, initial salary is commensurate with experience.
For PhD students: The Faculty of Sciences at Charles University is currently admitting PhD students bi-annually, earliest deadline to sign for PhD studies is in December 2020. In addition to a fellowship from the Charles University that is paid to students admitted to the graduate program, we offer a part-time position at IMG and corresponding salary with benefits.
Start of job:
Due to starting funding, the preferred start of appointment is January – February 2020 (could be negotiated for a strong candidate). Submit your application for a postdoc or PhD studies as soon as possible. Please submit your CV and a cover letter with a description of research experience and interests to Jana Dobrovolna (firstname.lastname@example.org). Be prepared to provide the names of three references.
Molecular mechanisms for maintaining the integrity of human genome under conditions of replication stress
The project will focus on molecular mechanisms involved in processing of highly genotoxic RNA:DNA hybrids, called R-loops, that are suspected to play role in cancer development. The candidate will identify the proteins associated with R-loops under conditions of chemically- and oncogene-induced replication stress and study their role in maintenance of genome stability. The project offers training in a broad range of molecular, cell biological and biochemical techniques. The student will also undergo short-term trainings at the Institute of Molecular Cancer Research of the University of Zurich where he/she will be exposed to front-line research in the field of DNA repair and cancer.
Candidate’s profile (requirements):
M.Sc. or equivalent in biochemistry or molecular/cellular biology, good English, independent thinking, strong interest in basic research and experimental work.
Supervisor: Jana Dobrovolná
Co-supervisor: Pavel Janščák
University of Zurich
Institute of Molecular Cancer Research
More information about the laboratory - www.imcr.uzh.ch.