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Laboratory of Protein Structure

Laboratory of Protein Structure

Leader
Marcin Nowotny, PhD, Professor

Leader

Our group studies the systems that process genetic information in living cells. This information is encoded in DNA and RNA. Special protein machines in the cell decode this information, ensure its stability and copy it. We study these machines at the level of individual chemical groups. For example, we have determined the molecular mechanisms of machineries that repair chemically damaged DNA or viral machineries that replicate genomes of the viruses.

Research Summary

Our group uses structural biology, mainly cryo-electron microscopy, and protein biochemistry to elucidate the mechanism of action of enzymes involved in the processing of genetic information encoded in DNA and RNA. In particular, we study DNA repair and transposition, reverse transcription, viral replication, RNA processing, and bacterial antiphage systems. For example, in our recent work we determined the molecular architecture of a key complex in one of the major DNA repair pathways in bacteria: homologous recombination. This complex, consisting of the RecF, RecR and RecO proteins, is responsible for the formation of a filament of single-stranded DNA and RecA. The latter promotes the search for homologous DNA in the repair process. We have also determined the structure and mechanism of action of unusual reverse transcriptases involved in the antiphage response – AbiK, Abi-P2, and AbiA. These enzymes are unique in that they produce long stretches of single-stranded DNA in a template and primer independent manner. They initiate synthesis by covalently attaching the first nucleotide to their tyrosine residue. Their other unique property is their ability to form hexamers and trimers.

RNases HDNA repairDNA transpositionReverse transcriptasesRNA processingNucleic acid‑based therapeuticsDrug development projects

 

Scientific Impact

The determination of the first structure of the bacterial homologous recombination complex RecFOR, explaining how it finds single-stranded double-stranded DNA junctions. The first structures of antiphage reverse transcriptases, revealing their hexameric/trimeric architecture and the mechanism of protein priming.

Future Goals

In the near future, we will continue our studies on DNA repair and transposition. We would like to fully elucidate the mechanism of action of the RecFOR complex and provide an understanding of the in vivo mechanism of antiphage reverse transcriptases.
 
 

Comment

"Our goal is to provide complete pictures of the mechanisms of action of certain DNA and RNA-processing pathways at the level of single atoms." — Marcin Nowotny, PhD, Professor

 

 




 

About the lab

mnowotny

Marcin Nowotny, PhD, Professor 

Correspondence address:
Laboratory of Protein Structure
International Institute of Molecular and Cell Biology
4 Ks. Trojdena Street, 02-109 Warsaw, Poland
Email: This email address is being protected from spambots. You need JavaScript enabled to view it. 
tel: +48 (22) 597 0717; fax: +48 (22) 597 0715

DEGREES

2020 - Professor of Biological Sciences, nomination by the President of the Republic of Poland
2013
- DSc Habil in Molecular Biology, Institute of Biochemistry and Biophysics, Warsaw, Poland
2002 - PhD in Biochemistry summa cum laude, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland (Supervisor: Jacek Kuźnicki)
1998 - MSc in Organic Chemistry and Biochemistry, Department of Chemistry, Warsaw University, Poland


PROFESSIONAL EMPLOYMENT

2025 - present - Deputy Director for Science, International Institute of Molecular and Cell Biology in Warsaw, Poland
2008 - present
- Professor, Head of the Laboratory of Protein Structure, International Institute of Molecular and Cell Biology in Warsaw, Poland
2017 - 2019 - Co-founder and Chief Scientific Officer, ProBiostructures, International Institute of Molecular and Cell Biology research service center for pharmaceutical industry
2016 - 2018 - Deputy Director for Science, International Institute of Molecular and Cell Biology in Warsaw, Poland

POSTDOCTORAL TRAINING

2003-2008 - Postdoctoral Fellow, Wei Yang Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA

MEMBERSHIP AND AWARDS

2024 - Polish Prime Minister Award for scientific achievement 
2023 - Jan Karol Parnas Award for the best Polish biochemical publication
2022 - Team Award for scientific achievement by the Minister of Education
2022 - Prize of the Foundation for Polish Science
2019
- Member, European Molecular Biology Organization
2019 - Member, Academia Europaea
2018 - Member, Scientific Policy Committee, Ministry of Science and Higher Education, Poland (in 2020 as a Chair)
2018 - MAESTRO, National Science Centre
2016 - TEAM, Foundation for Polish Science
2015 - Jan Karol Parnas Award for the best Polish biochemical publication (with the group of Prof. Janusz M. Bujnicki)
2013 - Academia Europaea Burgen Scholar
2013 - Knight’s Cross of the Order of Polonia Restituta
2012 - Polish Prime Minister Award for scientific achievement
2012 - Jan Karol Parnas Award for the best Polish biochemical publication
2012 - International Senior Research Fellowship, Wellcome Trust (renewal)
2012 - Early Career Scientist Award, Howard Hughes Medical Institute
2011 - ERC Starting Grant (2012-2017)
2007 - EMBO Installation Grant
2007 - International Senior Research Fellowship, Wellcome Trust
2003 - Prime Minister Award for PhD thesis
2001, 2002 - START Scholarship for Young Scientists, Foundation for Polish Science

DOCTORATES DEFENDED UNDER LAB LEADER’S SUPERVISION

M. Jaciuk, M. Miętus, M. Czarnocki-Cieciura, M. Śmietański, M. Rażew, S. Chamera, M. Gapińska, D. Malik

Group members

2025 Nowotny Lab

Lab Leader
Marcin Nowotny, PhD, Professor

Postdoctoral Researchers
Mariusz Czarnocki-Cieciura, PhD
Małgorzata Figiel, PhD
Markéta Šoltysová, PhD
Michał Tyras, PhD
Krzysztof Wycisk, PhD

Research Specialists
Łukasz Bałut, MSc
Akshata Kotwal, MSc
Julia Rybakowska, MSc
Małgorzata Sroka, MSc
Weronika Zajko, MSc

PhD Students
Girish Apte, MSc
Vysakh Komathattu Viswanath, MSc
Shuvankar Patra, MSc

Technician
Iwona Ptasiewicz (part-time)

Laboratory Support Specialist
Kamila Gajdek, MSc Eng

Laboratory of Zebrafish Developmental Genomics

Laboratory of Zebrafish Developmental Genomics

Leader
Cecilia L. Winata, PhD, Dsc Habil

Leader

Our research utilizes the zebrafish model organism to study how gene expression is regulated in the developing embryo, examining its links to congenital malformations in humans. We specifically focus on heart development and diseases, employing classical genetics alongside bulk and single-cell genomics techniques.

Research Summary

Intricate embryonic patterning is achieved through highly precise regulatory mechanisms that ensure controlled gene expression in the correct time and space. Our research aims to decipher the mechanism by which gene expression is regulated by transcription factors (TFs) and the epigenetic landscape. By exploring these mechanisms, we aim to illuminate how disruptions contribute to human congenital malformations. While key genetic factors that regulate the development and function of the heart are known, understanding their regulation, interactions, and coordination with epigenetic factors at different phases of heart development remains a gap. Our research focuses on cardiomyocytes and cardiac pacemaker cells.

Scientific Impact

We have generated transcriptomics and epigenomics resources of the developing zebrafish heart, covering the cardiomyocytes as well as rare cell types such as pacemakers. Our most recent work established a single cell transcriptome atlas of the developing zebrafish heart, revealing new cell types and their molecular profile. Additionally, our investigations have also revealed putative novel regulatory elements implicated in generating the cardiovascular cell diversity.

Future Goals

We aim to generate zebrafish models of human genetic diseases which could be used for in-depth studies to elucidate disease mechanisms or screening for potential therapies. Ultimately, we hope that our research could contribute to a better understanding of the complex molecular pathways underlying human congenital diseases.

Collaborations

We collaborate with labs within the IIMCB as well as externally. We also collaborate internationally with leading labs in the genomics and clinical genetics field.

Comment

“Eventually, we believe that our research in zebrafish must benefit humans. Therefore, we are always striving to select candidates which possess clinical relevance or potential for therapy.” - Cecilia Lanny Winata, PhD, DSc Habil

Laboratory Webpage

Lab pic

https://zfin.org/ZDB-LAB-141211-1

About the lab

JakubNo Photography 2016 02 22 1125 DSC 0250 Firefly Upscaler 2x scale
Jakub Nowak Photography; background modified.

Cecilia Lanny Winata, PhD, Dsc Habil

Correspondence address:
Laboratory of Zebrafish Developmental Genomics
International Institute of Molecular and Cell Biology
4 Ks. Trojdena Street, 02-109 Warsaw, Poland
Email: This email address is being protected from spambots. You need JavaScript enabled to view it. 
www: https://zfin.org/ZDB-LAB-141211-1
tel: +48 (22) 597 0768; fax: +48 (22) 597 0715

DEGREES

2021 - Dsc Habil in Biological Sciences, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

2009 - PhD in Biology, Department of Biological Sciences, National University of Singapore

2004 - BSc (Hons.) in Biology, Department of Biological Sciences, National University of Singapore

PROFESSIONAL EXPERIENCE
2014-present - Professor, Head, Zebrafish Developmental Genomics Laboratory, Max Planck/International Institute of Molecular and Cell Biology Research Group in Warsaw, Poland
2013-2014 - Research Associate, Genome Institute of Singapore (with 2013 research visit to laboratory of Prof. Peter Alestrom, Norwegian School of Veterinary Sciences, Oslo, Norway)
2009-2013 - Postdoctoral Fellow with Dr. Sinnakaruppan Mathavan, Genome Institute of Singapore
2004-2009 - Doctoral research with Prof. Gong Zhiyuan and Prof. Vladimir Korzh, Department of Biological Sciences, National University of Singapore

HONORS, PRIZES AND AWARDS

2016 - FIRST TEAM, Foundation for Polish Science
2016 - OPUS (as a partner), National Science Centre
2014 - OPUS, National Science Centre
2000-2004 - ASEAN Undergraduate Scholarship
2003 - Science Faculty Dean’s List, National University of Singapore

Group members

team2019

Lab Leader

  • Cecilia Lanny Winata, PhD

Postdoctoral Researchers

  • Shikha Vashist, PhD

  • Constantino Parisi, PhD

Research Technicians

  • Adrianna Pakuła, MSc

PhD Students

  • Aman Suryan, MSc

  • Arunabha Sen, MSc

Lab Technician

  • Julia Kędzierska, MSc

MsC Student

  • Konrad Kulesza, MSc

Laboratory Support Specialist

  • Agnieszka Konkol, MSc

Laboratory of Iron Homeostasis

Laboratory of Iron Homeostasis

Leader
Katarzyna Mleczko-Sanecka, PhD

Leader

Iron is essential for numerous biological processes, including oxygen transport, DNA synthesis, and cellular respiration. However, maintaining iron balance is crucial, as both iron deficiency and iron overload can lead to severe health issues. At the Laboratory of Iron Homeostasis, we investigate the mechanisms that regulate iron metabolism, focusing on iron recycling, sensing, and its impact on immune function and disease progression.

Research Summary

One aspect of our research focuses on iron recycling, mainly orchestrated by splenic red pulp macrophages (RPMs) that break down aging erythrocytes, releasing iron into the bloodstream. Despite being the primary iron source, limited knowledge exists about RPMs and the mechanisms influencing iron turnover efficacy. Our recent findings highlight the impairment of this process during aging. We demonstrated that age-related iron deposition in RPMs leads to their failure and demise, a challenge mitigated by dietary iron restriction in mice.

Another project explores unique functional and metabolic changes in RPMs in response to iron deficiency, aiding the organism's adjustment to restricted iron supplies. Concurrently, we investigate novel mechanisms in the sensing of body iron levels, particularly by specialized liver endothelial cells known as LSECs. We uncovered a new signaling pathway involving MAP kinases and the transcription factor ETS1, activated by excessive iron to amplify the expression of the well-known "iron sensor" Bmp6. Additionally, our research identifies LSECs as the primary cells removing free hemoglobin from circulation, playing a role in physiological iron recycling and hemoglobin detoxification under hemolytic conditions.

Scientific Impact

  • - Identified impairment of iron recycling as an early hallmark of aging.
  • - Discovered a new signaling pathway involved in iron sensing by liver endothelium.
  • - Uncovered a previously unknown role of liver endothelium in the clearance of free hemoglobin, operating both under physiological and hemolytic conditions.

Future Goals

  • - Explore the connections between iron recycling efficiency and splenic immune functions.
  • - Deepen our understanding of the diverse roles of liver endothelium in maintaining iron homeostasis.
  • - Further explore the adaptation of splenic macrophages to iron deficiency in health and disease.

Comment

"In our research, what we find particularly exciting is to realize that certain “dogmas” may only be partially accurate or even entirely false. This not only challenges existing beliefs but also creates opportunities to discover new principles in mammalian physiology that remain incompletely understood.", says Dr. Katarzyna Mleczko-Sanecka.


LHZ picture

Primary murine LSECs performing uptake of fluorescentlylabeled hemoglobin. Illustration by Aneta Jończy.

About the lab

sanecka

Katarzyna Mleczko-Sanecka, PhD 

Correspondence address:
Laboratory of Iron Homeostasis
International Institute of Molecular and Cell Biology
4 Ks. Trojdena Street, 02-109 Warsaw, Poland
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
tel: +48 (22) 597 0776; fax: +48 (22) 597 0715

DEGREES

2011 - PhD in Biology, European Molecular Biology Laboratory (EMBL) Heidelberg and Heidelberg University, Germany
2007 - MSc in Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland

PROFESSIONAL EXPERIENCE

2017-present - Professor, Head of Laboratory of Iron Homeostasis, International Institute of Molecular and Cell Biology in Warsaw, Poland
2011-2015 - Postdoctoral research with Prof. Martina Muckenthaler and Prof. Matthias W. Hentze, Molecular Medicine Partnership Unit, European Molecular Biology Laboratory and Heidelberg University, Heidelberg, Germany
2007-2011 - Doctoral research with Prof. Martina Muckenthaler and Prof. Matthias W. Hentze, Molecular Medicine Partnership Unit, European Molecular Biology Laboratory and Heidelberg University, Heidelberg, Germany
2006-2007 - Master thesis research with Prof. Józef Dulak and Prof. Alicja Józkowicz, Department of Medical Biotechnology, Jagiellonian University, Cracow, Poland
2006 - Undergraduate research during Erasmus fellowship with Dr. Claudine Kieda, Centre De Biophysique Moleculaire, Centre National de la Recherche Scientifique, Orleans, France
2005 - Undergraduate research during Erasmus scholarship with Dr. Claudine Kieda, Centre De Biophysique Moleculaire, Centre National de la Recherche Scientifique, Orleans, France

HONORS, PRIZES AND AWARDS

2023 - Awarded as a Co-investigator in the American Federation for Aging Research (AFAR) grant
2023 - Gunshin Levy Award from the BioIron Society
2021 - NCN SONATA BIS 10 Grant
2020 - Scholarship of the Minister of Science and Higher Education for Outstanding Young Scientist
2019 - NCN OPUS 16 Grant
2016 - POLONEZ, National Science Centre
2014 - Independent research grant, University of Heidelberg
2011 - Invitation to 61st Lindau Meeting of Nobel Laureates, Lindau, Germany
2015, 2014, 2011-2009 - Travel Grant to attend and present data at the international conferences in iron biology
2007 - Louis-Jeantet PhD Scholarship for young researchers from Eastern Europe to support PhD studies at European Molecular Biology Laboratory
2006 - Erasmus Scholarship, Centre National de la Recherche Scientifique, Orleans, France

Group members

team2019

Lab Leader:

  • Katarzyna Mleczko-Sanecka, PhD

Post-doc:

  • Aneta Jończy, PhD

PhD Students:

  • Komal Kumari Chouhan, MSc

  • Raghunandan Mahadeva, MSc

Research Specialist:

  • Marta Niklewicz, MSc

Technician:

  • Iwona Łopata, MSc

Laboratory Support Specialist:

  • Patrycja Rojek, PhD

Laboratory of Protein Metabolism

Laboratory of Protein Metabolism

Leader
Wojciech Pokrzywa PhD, Professor

Leader

Our research is centered on the dynamics of proteostasis, the balance between protein synthesis, folding, trafficking, and degradation, and how its disruption drives disease. We focus on how cells decide the fate of newly made proteins, with particular emphasis on translation control, the ubiquitin-proteasome system (UPS), and molecular chaperone networks as an integrated quality-control system. A major direction of our work is the molecular basis of rare diseases caused by defects in protein quality control, especially those linked to UPS dysfunction, including disorders associated with genes such as FEM1C or PIGV. We also investigate organelle-specific proteostasis, particularly within the nucleolus, to understand how cells reorganize essential compartments during stress, recovery, and disease. To address these questions, we combine biochemical assays, advanced microscopy, molecular genetics, and bioinformatics in mammalian cell models and the nematode Caenorhabditis elegans, leveraging IIMCB’s state-of-the-art core facilities.

OUR RESEARCH

Rare Diseases of Proteostasis

A central, ongoing research programme of the laboratory focuses on elucidating the molecular basis of rare human diseases arising from defects in protein quality control and ubiquitin-dependent regulation. We are systematically investigating disorders linked to dysfunction of ubiquitin ligases, with particular emphasis on cullin-RING E3 ligase substrate receptors. Our work addresses how impaired substrate recognition destabilises tissue-specific proteomes and leads to multisystem phenotypes encompassing neurodevelopmental, muscular, and metabolic pathologies.

Building on these studies, we are expanding our efforts to include rare metabolic disorders that intersect functionally with proteostasis, including PIGV-related disease and related glycosylation- and lipid-linked syndromes. By integrating patient-derived genetic data with quantitative proteomics and in vivo functional modelling in C. elegans, we are defining shared molecular principles that connect ubiquitination, metabolism, and organismal homeostasis, with the long-term goal of enabling improved diagnostics and mechanism-informed therapeutic strategies. We focus on deciphering mechanisms that alter the abundance and types of cellular messenger RNAs and proteins because these kinds of molecules are critical for live-or-die decisions of the cell. We are also investigating the role of protein quality control networks and the ubiquitin system during C. elegans recovery from cold stress. We also conduct drug screens to identify molecules that support the ability of C. elegans to survive cold stress.

Nucleolus as a Stress-Responsive Hub

An ongoing research focus of the laboratory is the role of the nucleolus as an active, stress-responsive regulator of proteostasis. We are investigating how proteotoxic stress induces a reversible reorganisation of the nucleolus into a specialised protein quality control compartment that transiently prioritises proteome protection over ribosome biogenesis.

Our work aims to define how nucleolar remodelling integrates protein folding, ubiquitination, sequestration, and controlled recovery, generating distinct nucleolar states that encode proteostasis capacity and readiness to resume biosynthetic activity. By linking structural plasticity of the nucleolus to adaptive stress responses, this project positions ribosome biogenesis as a dynamically regulated process and identifies the nucleolus as a central coordination hub safeguarding cellular homeostasis during and after stress.

Proteostasis under Chronic Stress

Our laboratory is actively investigating how cells and tissues maintain proteome integrity under prolonged or recurrent proteotoxic stress. When degradation capacity becomes limiting, organisms must adopt adaptive strategies that extend beyond transient heat-shock or unfolded protein responses. A key objective of this project is to define how proteostasis is preserved when growth and biosynthesis must be temporarily deprioritised in favour of survival.

We are characterising stress-adaptive programmes that involve spatial reorganisation of protein quality control, selective stabilisation of damaged proteomes, and delayed recovery processes reminiscent of dormancy or hibernation-like states. Through a combination of genetics, live imaging, and quantitative proteomics, we aim to determine how these strategies sustain tissue function over time and how their failure contributes to ageing and degenerative disease.

Lipids-Proteasome Axis in Stress & Ageing

An active line of investigation in the laboratory examines how lipid metabolism regulates protein degradation during chronic stress and ageing. We are dissecting a conserved lipid-proteasome axis in which modulation of lipid biosynthetic pathways stabilises proteasome function and preserves cellular fitness under sustained proteotoxic conditions, challenging the traditional view of metabolism as a passive energy supplier to protein quality control.

Using C. elegans and human cell systems, we are analysing how lipid composition and inter-tissue lipid signalling reshape proteostasis networks during prolonged stress. This work aims to define how metabolic rewiring supports long-term survival when canonical stress responses become insufficient, and how similar mechanisms may contribute to pathological adaptations such as resistance to proteasome-targeting therapies in cancer.

FUTURE GOALS

Our laboratory aims to define how the ubiquitin–proteasome system, nucleolar remodelling, and metabolic state jointly govern stress adaptation, ageing, and rare-disease phenotypes, including tissue- and stress-specific rules of substrate selection and degron logic. We integrate patient genetics with quantitative proteomics, targeted bioinformatic discovery, and C. elegans functional modelling and screening to facilitate the discovery of targeted therapies.

COMMENT

"Our research efforts are dedicated to unraveling the complex molecular mechanisms of proteostasis and cellular adaptation, setting the stage for groundbreaking discoveries in biological science and new therapeutic strategies.” — Wojciech Pokrzywa, PhD, DSc Habil

SOCIAL IMPACT

Inspired by rare disease research carried out in his laboratory at the IIMCB, Prof. Wojciech Pokrzywa founded LumiRare (https://lumirare.com). The company translates scientific expertise into tailored reports for families affected by rare genetic variants, helping them better understand disease mechanisms, explore possible directions for further research, and connect with relevant experts and laboratories.

THE LABORATORY WEBSITE

WP LAB www
     pokrzywalab.com   

About the lab

wpokrzywa

Prof. Wojciech Pokrzywa, PhD, Habil 

Correspondence address:
Laboratory of Protein Metabolism 
International Institute of Molecular and Cell Biology in Warsaw
4 Ks. Trojdena Street, 02-109 Warsaw, Poland
Email: This email address is being protected from spambots. You need JavaScript enabled to view it. |
www: pokrzywalab.com
tel: +48 (22) 597 0742

DEGREES

2026 - Professor of Exact and Natural Sciences in the discipline of Biological Sciences, nomination by the President of the Republic of Poland
2020
- DSc Habil in Biological Sciences, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Poland
2009 - PhD in Biological Engineering and Agronomic Sciences at the Institute of Life Sciences, Molecular Physiology Group (FYMO), Catholic University of Louvain, Belgium.
2006 - Master of Advanced Science in Biological Engineering and Agronomic Sciences at the Catholic University of Louvain, Belgium.
2004 - Master’s in Microbiology at the University of Wroclaw, Poland.

PROFESSIONAL EXPERIENCE

2017 - present - Professor, Head of Laboratory of Protein Metabolism, International Institute of Molecular and Cell Biology in Warsaw, Poland
2009 - 2017 - Postdoctoral fellow at the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany.
2004 - 2008 - PhD studies at the Institute of Life Sciences, Molecular Physiology Group (FYMO), Catholic University of Louvain, Belgium.

HONORS, PRIZES AND AWARDS

2024 - A distinction from the Division II of the Polish Academy of Sciences for the “Discovery of new proteostasis mechanisms important in the functioning of organisms and development of new therapies”
2024
- The Minister of Science and Higher Education award for outstanding scientific achievement 
2022
- SONATA BIS, National Science Center
2020
- GRIEG, National Science Center
2018 - FIRST TEAM, Foundation for Polish Science
2018 - EMBO Installation Grant
2017 - OPUS, National Science Centre
2005 - PhD Fellowship from the FNRS-Fund for Scientific Research, Belgium
2004 - ERASMUS Scholarship

Group members

Lab Leader

  • Prof. Wojciech Pokrzywa, PhD, DSc Habil

Postdocs

  • Andrés Felipe Leal Bohórquez, Ph.D.
  • Bogdan Cichocki, Ph.D.
  • Małgorzata Piechota, Ph.D.
  • Agnieszka Sztyler, Ph.D.
  • Pankaj Thapa, Ph.D.

PhD Students

  • Lilla Biriczová, M.Sc.
  • Karolina Milcz, M.Sc.
  • Smriti Raina, M.Sc
  • Anwesha Sarkar, M.Sc
  • Natalia Szulc, M.Sc.

Specialists

  • Kushboo Jaggi, M.Sc.
  • Marta Niklewicz, M.Sc.
  • Gabriela Skrzyńska, M.Sc.

Laboratory of RNA Biology - ERA Chairs Group

Laboratory of RNA Biology - ERA Chairs Group

Leader
Andrzej Dziembowski, PhD, Professor

Leader

We are molecular biologists who are trying to understand how the stability of mRNA is regulated. We have recently discovered a previously overlooked mechanism that increases the stability of both naturally produced and therapeutic mRNA (like mRNA vaccines), operating only in specific cell types and tissues. In the future, we plan to understand this new mechanism better and exploit it to design more effective mRNA-based therapeutics.

Research Summary 

Although mRNA degradation has been studied for years, and the major decay pathways conserved between eukaryotes are already established, we know very little about how these are integrated in vivo. The stability of mRNA is mainly controlled by the dynamics of 3’ terminal poly(A) tails initially synthesized in the nucleus. At the same time, the analysis of poly(A) tails is challenging as for any other homopolymeric tract. In the lab, we implemented direct RNA sequencing on nanopores to study the metabolism of poly(A) tails. This methodology enables us to look more comprehensively at the dynamics of poly(A) tails in vivo. We discovered that a metazoan-specific family of cytoplasmic poly(A) polymerases (TENT5) that by extending mRNA's tails play crucial roles in mammalian physiology. TENT5B, C, and D participate in gametogenesis, while TENT5A regulates collagen expression in osteoblasts. In immune cells, TENT5A and C enhance the expression of innate immunity effector proteins. Notably, we have recently described the unexpected role of TENT5A in the regulation of the stability of anti-COVID19 mRNA vaccine.

Scientific Impact 

- Description of TENT5 cytoplasmic poly(A) polymerases as important regulators of physiological processes. 
- Discovery that TENT5A re-adenylates and stabilizes anti-SARS-CoV-2 mRNA vaccine, enhancing antigen production and vaccine efficacy.

Future Goals

Within the framework of the recently-funded ERC Advanced Grant ViveRNA, we plan to comprehensively study the stability of both endogenous and therapeutic mRNA in vivo. We will enhance the accuracy of the methods used to determine the properties of mRNAs, especially computational protocols for the analysis of poly(A) tails. These, combined with carefully designed transgenic mouse models, primary cell cultures, and synthetic biology approaches, should, in the future, enable the design of next-generation mRNA therapeutics. In parallel, together with our collaborators from the Virtual Research Institute, we are actively working on improving mRNA-based therapies using chemical approaches and applying them for cancer immunotherapy.

Collaborations

Our lab coordinates a large Virtual Research Institute project, the Horizon for Excellence in messenger RNA applications in immunoOncology (HERO). Within HERO, we collaborate with Marcin Nowotny and Marta Miączyńska from our Institute, Jacek Jemielity, and Joanna Kowalska from the University of Warsaw, as well as Dominika Nowis and Jakub Gołąb from the Warsaw Medical University. At the same time, we have several other ongoing collaborations. These mainly focus on mRNA stability and include Magdalena Dziembowska (University of Warsaw), Bertrand Séraphin (IGBMC, France), Agnieszka Tudek (IBB Warsaw), Torben Jensen (Aarhus University), and Greg Kudla (HGU, UK).

Comment

"We are very intrigued by the fact that although the machinery involved in mRNA metabolism is the same everywhere, there is high variability in mRNA stability and poly(A) tail dynamics in all tissues. This is reflected, for instance, by high differences in the average lengths of poly(A) tails depending on the cell type. Understanding of this variation is particularly important in the context of future applications for mRNA-based therapeutics," says Andrzej Dziembowski, PhD, Professor

 

fot lab JB copy

We aim to use nanopore sequencing to identify factors that affect mRNA stability. This will allow the design of better therapeutic mRNAs to help fight diseases. Illustration by Natalia Gumińska

 

Visit the laboratory profile on X: https://twitter.com/DziembowskiLab

About the lab

 ad2019

Andrzej Dziembowski, PhD, Professor

Correspondence address:
Laboratory of RNA Biology - ERA Chairs Group
International Institute of Molecular and Cell Biology in Warsaw
4 Ks. Trojdena Street, 02-109 Warsaw, Poland
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.  
www: https://mosaic.iimcb.gov.pl & crisprmice.eu    

          Mosaic logo

DEGREES:

2014 - Professor of Biological Sciences, nomination by the President of the Republic of Poland
2009 - DSc Habil in Molecular Biology, University of Warsaw, Poland
2002 - PhD in Biology, cum laude, Department of Genetics Faculty of Biology, University of Warsaw, Poland
1998 - MSc in Molecular Biology, University of Warsaw, Inter-Faculty Individual Studies in Mathematics and Natural Sciences, Poland

PROFESSIONAL EMPLOYMENT:

2019-present - Professor, Head of the Laboratory of RNA Biology - ERA Chairs Group, IIMCB, Warsaw, Poland (100% appointment)
2011-present - Associate Professor, Faculty of Biology, Department of Genetics and Biotechnology, University of Warsaw, Poland (currently 25% employment)
2014-2019 - Full Professor, Institute of Biochemistry and Biophysics PAS, Poland
2010-2014 - Associate Professor, Institute of Biochemistry and Biophysics PAS, Poland
2008-2010 - Assistant Professor, Institute of Biochemistry and Biophysics PAS, Poland
2006-2011 - Assistant Professor, Faculty of Biology, Department of Genetics and Biotechnology, University of Warsaw, Poland
2002 -2006 - Post-doctoral fellow, Centre de Génétique Moléculaire, CNRS, France

MEMBERSHIP IN SCIENTIFIC SOCIETIES, ORGANIZATIONS AND PANELS:

2020 - Corresponding Member, Polish Academy of Sciences
2018 - EMBO Member
2004 - Member, RNA society

FELLOWSHIPS AND AWARDS:

2018 - Prize for scientific achievements, Foundation for Polish Science
2014 - Master Award, Foundation for Polish Science
2013 - Ideas for Poland Award, Foundation for Polish Science
2013 - Knight's Cross of the Order of Polonia Restituta
2013 - Jakub Karol Parnas Award for the best publication in biochemistry, Polish Biochemical Society
2013 - National Science Centre Award for outstanding scientific achievements
2012 - Member, Polish Young Academy, Polish Academy of Sciences
2010 - Prime Minister Award for the habilitation thesis
2009 - Scholarship for outstanding young scientists, Minister of Science and Higher Education
2006 - EMBO Installation Grant
2002 - Postdoctoral fellowship, Foundation for Polish Science
2002 - Prime Minister Award for PhD thesis
2001 - Scholarship for Young Scientists, Foundation for Polish Science

DOCTORATES DEFENDED UNDER LAB LEADER’S SUPERVISION:

K. Drążkowska, M. Lubas, A. Siwaszek, M. Ukleja, M. Czarnocki-Cieciura, O. Gewartowska, P. Krawczyk, E. Furmańczyk, A. Pyzik, T. Kuliński.


 MOSaIC logotypy

The Laboratory of RNA Biology - ERA Chairs Group has been established thanks to the EU H2020 funding within the ERA Chairs project
entitled “MOlecular Signaling in Health and Disease - Interdisciplinary Centre of Excellence”, acronym: MOSaIC (GA no 810425)

 

Group members

group2019


Lab Leader: 

  • Andrzej Dziembowski, PhD, Professor

Senior Scientist:

  • Seweryn Mroczek, PhD

Postdoctoral Researchers:

  • Aleksandra Brouze, PhD

  • Natalia Gumińska, PhD

  • Paweł Krawczyk, PhD

  • Tomasz Kuliński, PhD

  • Katarzyna Matylla-Kulińska, PhD

  • Bartosz Tarkowski, PhD

Research Assistant:

  • Paula Castañeda Londoño, MSc

  • Karolina Kasztelan, MSc 

Senior Specialist:

  • Kamila Affek, MSc

  • Agnieszka Czarnocka-Cieciura,MSc

  • Ewelina Patrycja Owczarek, MSc

Junior Specialist:

  • Dominik Chwastek, MSc

  • PhD Students:

    • Wiktor Antczak, MSc

    • Zuzanna Mackiewicz, MSc

    • Michał Mazur, MSc

    • Tola Tame, MSc

    Volunteers:

    • Monika Kusio-Kobiałka, PhD

    • Ewa Poniecka, PhD

    • Julia Gilewska, MSc student

    • Marcin Małkowski, PhD student of University of Warsaw

    • Maria Nizik, MSc student

    • Wiktoria Orzeł, PhD student of University of Warsaw

    Lab Technician:

    • Alina Zielińska, BSc

    Laboratory Support Specialist:

    • Paula Kwapisz, MSc


    MOSaIC logotypy

    The Laboratory of RNA Biology - ERA Chairs Group has been established thanks to the EU H2020 funding within the ERA Chairs project
    entitled “MOlecular Signaling in Health and Disease - Interdisciplinary Centre of Excellence”, acronym: MOSaIC (GA no 810425)

  1. Laboratory of RNA-Protein Interactions - Dioscuri Centre
  2. Laboratory of Prokaryotic Gene Regulation
  3. Laboratory of Cellular Genomics
  4. Laboratory of Cellular Proteostasis

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