Leader

Ewelina Małecka, PhD

Leader

Our lab investigates the molecular choreography of post-transcriptional gene regulation in bacteria, focusing on the critical moments when these networks are challenged by stress or viral attack. Our research spans from the molecular level, where we use single-molecule microscopy to visualize the assembly of protein-RNA complexes in real time, to the cellular level, where we use bacteriophages to identify novel antibacterial strategies. This integrated approach is applied to commensal and pathogenic E. coli as well as high-priority pathogens like antibiotic-resistant Acinetobacter baumannii.

Research Summary

Our research program deciphers the rules of bacterial gene expression across multiple scales. At the molecular level, we use biochemical methods and advanced single-molecule TIRF microscopy to dissect how small regulatory RNAs and the RNA chaperone Hfq function. By capturing real-time interactions between proteins, ribosomes, and RNAs, we seek to understand the fundamental principles governing bacterial gene expression. We then bridge this deep mechanistic insight to the systems level by studying the effects of bacteriophage infection. Here, we deploy transcriptomic and proteomic studies to reveal novel vulnerabilities that can be potentially targeted for antibacterial design. Our work is supported by a Sonata Bis grant from the National Science Centre, Poland and EMBO Installation Grant.

Scientific Impact

- Mechanistic insights: our work provides a mechanistic understanding of how sRNAs select targets and orchestrate gene silencing. By dissecting the dynamics of targeting and degradation, we move beyond static models to reveal fundamental principles of regulatory control in bacteria.
- Cutting-edge technology: we are using a state-of-the-art microscope to monitor single molecules in action. RNA targeting, translation, and degradation can be visualized simultaneously in real time.
- Potential applications: our work on phage-encoded factors targeting antibiotic-resistant bacteria may unlock new antimicrobial strategies against ESKAPE pathogens. Understanding sRNA design rules will enable the development of programmable bacterial regulators for synthetic biology, metabolic engineering, and targeted therapeutic interventions.

Future Goals

Looking ahead, our research will bridge fundamental discovery with therapeutic innovation. We aim to expand our single-molecule analysis to capture the entire regulatory journey of an mRNA, from its initial targeting by sRNA-Hfq complexes to its ultimate fate at the ribosome. We will leverage this deep mechanistic insight to dissect the phage-host arms race in more clinically relevant contexts, such as within ESKAPE pathogens.

Collaborations

We collaborate with Prof. Sander Granneman (University of Edinburgh) to integrate single-molecule visualization with in vivo protein-RNA mapping, and with Prof. Ben Luisi (University of Cambridge) to connect regulatory dynamics to the mechanics of RNA degradation.

Comment

"The central challenge of modern biology is to understand how molecular processes are interconnected at the molecular level within the cellular environment. We're tackling this by visualizing individual RNAs and proteins as they orchestrate bacterial gene regulation – a system of incredible precision and speed. Watching these decisions unfold one molecule at a time reveals the elegant strategies that have ensured bacterial survival for billions of years," says Ewelina Małecka.

Visit the laboratory website for more details: https://maleckalab.com/

About the lab

Ewelina Małecka, PhD Correspondence address: Laboratory of Prokaryotic Gene Regulation International Institute of Molecular and Cell Biology in Warsaw 4 Ks. Trojdena Street, 02-109 Warsaw, Poland https://maleckalab.com/ Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

DEGREES

2017 - PhD in Biochemistry with Prof. Mikołaj Olejniczak, Adam Mickiewicz University, Poznań, Poland

2012 - MSc in Biotechnology with Prof. Zofia Szweykowska-Kulińska, Adam Mickiewicz University, Poznań, Poland

PROFESSIONAL EXPERIENCE

2022 - present - Head of Laboratory of Prokaryotic Gene Regulation (former: Single-Molecule Biophysics), International Institute of Molecular and Cell Biology in Warsaw, Poland

2022 - present - Visiting Researcher, Dept. of Biochemistry, Johns Hopkins University, US

2017 - 2022 - Postdoctoral fellow with Prof. Sarah Woodson, Dept. of Biochemistry, Johns Hopkins University, USA

HONORS, PRIZES, AND AWARDS

2024-2029 EMBO Installation Grant

2023-2028 Sonata Bis grant (National Science Centre)

2023-present Member of the NAR Early Career Researcher Advisory Board

2022 - Invited panelist "Diverse Voices from Rising Scientists", RNA Society meeting, Boulder, USA

2022 - RNA Society Research Presentation Fellowship

2021 - Invited interview with Molecular Cell "Meet the authors", doi: 10.1016/j.molcel.2021.04.011

2021 - Early-career reviewer in Elife (Structural Biology and Molecular Biophysics)

2021 - Conference Award, RNA Society

2019 - Travel Award, RNA Society

2018 - Travelling Fellowship, The Company of Biologists

2015 - present - Member, RNA Society

2015-2018 Preludium grant (National Science Centre) 

PUBLICATIONS BY DR. EWELINA MAŁECKA PRIOR TO JOINING IIMCB:

1. Małecka EM, Woodson SA.
   RNA compaction and iterative scanning for small RNA targets by the Hfq chaperone.
   Nat Commun. 2024 Mar 7;15(1):2069.
   doi:10.1038/s41467-024-46316-6.

2. Sarni SH, Roca J, Du C, Jia M, Li H, Damjanovic A, Małecka EM, Wysocki VH, Woodson SA.
   Intrinsically disordered interaction network in an RNA chaperone revealed by native mass spectrometry.
   Proc Natl Acad Sci U S A. 2022 Nov 22;119(47):e2208780119.
   doi: 10.1073/pnas.2208780119.

3. Małecka EM, Hua B, Woodson SA.
   Single-Molecule FRET Studies of RNA Structural Rearrangements and RNA-RNA Interactions.
   Methods Mol Biol. 2022;2518:271-289.
   doi: 10.1007/978-1-0716-2421-0_16.

4. Małecka EM, Sobańska D, Olejniczak M.
   Bacterial Chaperone Protein Hfq Facilitates the Annealing of Sponge RNAs to Small Regulatory RNAs.
   J Mol Biol. 2021 Nov 19;433(23):167291.
   doi: 10.1016/j.jmb.2021.167291.

5. Malecka EM, Bassani F, Dendooven T, Sonnleitner E, Rozner M, Albanese TG, Resch A, Luisi B, Woodson S, Bläsi U.
   Stabilization of Hfq-mediated translational repression by the co-repressor Crc in Pseudomonas aeruginosa.
   Nucleic Acids Res. 2021 Jul 9;49(12):7075-7087.
   doi: 10.1093/nar/gkab510.

6. Małecka EM, Woodson SA.
   Stepwise sRNA targeting of structured bacterial mRNAs leads to abortive annealing.
   Mol Cell. 2021 May 6;81(9):1988-1999.e4.
   doi: 10.1016/j.molcel.2021.02.019.

7. Panja S, Małecka EM, Santiago-Frangos A, Woodson SA.
   Quantitative Analysis of RNA Chaperone Activity by Native Gel Electrophoresis and Fluorescence Spectroscopy.
   Methods Mol Biol. 2020;2106:19-39.
   doi: 10.1007/978-1-0716-0231-7_2.

8. Małecka EM, Woodson SA.
   Ribosomes clear the way for siRNA targeting.
   Nat Struct Mol Biol. 2020 Sep;27(9):775-777.
   doi: 10.1038/s41594-020-0495-4.

9. Santiago-Frangos A, Fröhlich KS, Jeliazkov JR, Małecka EM, Marino G, Gray JJ, Luisi BF, Woodson SA, Hardwick SW.
   Caulobacter crescentus Hfq structure reveals a conserved mechanism of RNA annealing regulation.
   Proc Natl Acad Sci U S A. 2019 May 28;116(22):10978-10987.
   doi: 10.1073/pnas.1814428116.

10. Małecka EM, Stróżecka J, Sobańska D, Olejniczak M.
    Structure of bacterial regulatory RNAs determines their performance in competition for the chaperone protein Hfq.
    Biochemistry. 2015 Feb 10;54(5):1157-70.
    doi: 10.1021/bi500741d.

11. Sobkowiak L, Bielewicz D, Malecka EM, Jakobsen I, Albrechtsen M, Szweykowska-Kulinska Z, Pacak A.
    The Role of the P1BS Element Containing Promoter-Driven Genes in Pi Transport and Homeostasis in Plants.
    Front Plant Sci. 2012 Mar 30;3:58.
    doi: 10.3389/fpls.2012.00058.

Group members

Group Leader:
Ewelina Małecka, PhD

Postdoctoral Researcher:
Maciej Dylewski, PhD

PhD Students:
Ewa Izdebska
Aiswarya Mohan

Junior Research Scientist:
Daria Demina

Intern:
Sebastian Machera

Msc student:
Zuzanna Grzegorczyk

Laboratory Support Specialist:
Karolina Komorowska

Technician:
Katarzyna Kaca

Leader

Aleksandra Kołodziejczyk, PhD

Leader

Research Areas 

Gut-liver axis

We are investigating the bidirectional crosstalk between the liver and the intestine, focusing on the role of resident microbiota. We explore how shifts in bacterial composition and changes in intestinal physiology affect liver cells and how liver health contributes to the homeostasis in the gut.

Microbiota-derived metabolites

We are exploring the role of microbiota-derived metabolites in the host physiology. We focus on the molecular mechanisms by which metabolites affect cellular functions.

Chronic inflammation

We are interested in the mechanisms underlying chronic inflammatory processes accompanying organ fibrosis, metabolic syndrome and autoimmune disorders. Particularly, we are focusing on the role of stromal cells and their interactions.

Key Approaches

Multi-omics

We are developing and adopting sequencing-based methods to comprehensively study host cellular phenotypes and microbiota states (single-cell RNA-seq, ATAC-seq, ChIP-seq, metagenomics). We complement and integrate these data with metabolomics to generate comprehensive multimodal characterisation.

Genetic screening

To identify molecular mechanisms underlying interactions between the host and the microbiota, we are establishing in vitro high-throughput screening methods in cell lines and organoids.

Data mining

We use and develop advanced bioinformatics approaches to generate insights and predictions from our multi-omic data. Moreover, in the spirit of ‘data parasitism’ we are integrating and reusing underutilised published datasets to generate novel discoveries.  

Visit the laboratory website for more details: olab.com.pl 

About the lab

Aleksandra Kołodziejczyk, PhD Correspondence address: Laboratory of Cellular Genomics International Institute of Molecular and Cell Biology in Warsaw 4 Ks. Trojdena Street, 02-109 Warsaw, Poland www: olab.com.pl Email:  This email address is being protected from spambots. You need JavaScript enabled to view it.

Group members

Group Leader
Aleksandra Kołodziejczyk, PhD

Postdoctoral researchers:
Krzysztof Szczepaniak, PhD 
Aneta Grymanowska, PhD 

PhD Students
Joanna Słota 
Aleksandra Uryga 
Konstacja Gałat 
Anna Węgrzycka 
Natalia Rzepka 

Undergraduate Students:
Zofia Link 
Joanna Siatecka 

Laboratory Support Specialist:
Karolina Komorowska

Research Coordinators:
Martyna Wysokińska
Anna Majerowicz

Leader

Lidia Wróbel, PhD

Leader

Our laboratory investigates how cells maintain the health of their proteome – a process known as proteostasis. We are particularly interested in the spatial and temporal regulation of protein degradation pathways in mammalian cells. We aim to understand how disruptions in these quality control systems contribute to the development of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s disease.

Research Summary

The cellular proteome is extraordinarily complex, comprising thousands of proteins that must be correctly folded, localized, and removed when damaged or no longer needed. This balance – proteostasis – is maintained by coordinated systems controlling protein synthesis, quality control, and degradation. Our laboratory focuses on the mechanisms governing protein clearance, particularly the ubiquitin-proteasome system (UPS), and how they are regulated across different cellular compartments.

Our research aims to dissect the molecular pathways that maintain nuclear protein quality control and to understand how these pathways interact with cytosolic degradation systems. We are especially interested in the nucleocytoplasmic transport of UPS components, including the unfoldase VCP/p97. Impaired communication between nuclear and cytosolic proteostasis networks may contribute to the early stages of neurodegeneration, yet the molecular underpinnings of this phenomenon remain poorly understood.

To investigate these mechanisms, we use a combination of cutting-edge molecular biology, high-throughput CRISPR/Cas9-based genetic screening, quantitative mass spectrometry, and advanced fluorescence microscopy. We apply these tools to cellular models of neurodegenerative diseases, including human iPSC-derived neurons and brain organoids. Our ultimate goal is to identify how proteostasis networks fail in disease and to uncover new therapeutic strategies aimed at restoring protein homeostasis in affected cells.

Fig.: Primary pathways for protein degradation in the cytosol and nucleus

Scientific Impact

• - Identification of mechanisms regulating nuclear proteostasis and their crosstalk with cytosolic degradation pathways.
• - New insights into how alterations in protein clearance pathways contribute to neurodegenerative disease pathology.
• - Development and application of human neuronal models to study disease-associated proteostasis defects.

Future Goals

We aim to define how the ubiquitin-proteasome system functions within the nucleus and how nuclear proteostasis is integrated with broader cellular protein quality control. Our research will also explore how impairments in these systems lead to the accumulation of toxic protein aggregates – a hallmark of many neurodegenerative diseases. Ultimately, we hope to identify novel molecular targets for therapies that can restore cellular proteostasis in disease-affected tissues.

Collaborations

We actively seek interdisciplinary collaborations to bridge molecular proteostasis research with translational neuroscience. Our partnerships include experts in neurobiology, cellular imaging, proteomics, and regenerative medicine. Collaborative efforts are focused on uncovering therapeutic targets and validating findings in disease-relevant human models.

Comment

“Our goal is to understand how cells regulate the quality and clearance of proteins, especially in the nervous system. Unraveling the molecular causes of proteostasis failure in neurons may open new therapeutic avenues for currently incurable neurodegenerative diseases,” - Dr. Lidia Wróbel, Head of the Laboratory of Cellular Proteostasis.

Laboratory Webpage

https://wrobel-lab.iimcb.gov.pl/

About the lab

Lidia Wróbel, PhD Correspondence address: Laboratory of Cellular Proteostasis 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.wrobel-lab.iimcb.gov.pl

DEGREES

2015 - PhD in Biological Sciences, Nencki Institute of Experimental Biology, Warsaw, Poland
2009 - Msc in Biotechnology, Warsaw University of Life Sciences, Poland

PROFESSIONAL EXPERIENCE

2024- present - Head of Laboratory of Cellular Proteostasis, International Institute of Molecular and Cell Biology in Warsaw, Poland
2016-2024 – Postdoctoral research with Prof. David Rubinsztein at Cambridge Institute for Medical Research/UK Dementia Research Institute, University of Cambridge, United Kingdom
2010-2015 – Doctoral research with Prof. Agnieszka Chacińska, International Institute of Molecular and Cell Biology in Warsaw, Poland (with 2013-20014 research visit to laboratory of Prof. Trevor Lithgow at Monash University, Melbourne, Australia and with 2012 research visit to laboratory of Prof. Bettina Warscheid at Faculty of Biology and BIOSS Centre for Biological Signaling, University of Freiburg, Germany)
2008-2009 – Master thesis research with Prof. Bart Braeckman, Laboratory of Aging Physiology and Molecular Evolution, Ghent University, Belgium

HONORS, PRIZES AND AWARDS

2025- Habilitation fellowship of L’Oréal Poland for Women in Science
2025 - EMBO Installation Grant
2024 – SONATA, National Science Centre
2016 – Conference Award, Gordon Research Seminar on Mitochondria and Chloroplasts
2016 – EMBO Long Term Fellowship
2016 - Drabikowski Award for the best PhD thesis
2014 – Travelling Fellowship, EMBO/EMBL Symposia Series
2014 – Conference Award, Lorne Conference on Protein Structure and Function
2013  - Etiuda I PhD Scholarship, National Science Centre
2012 – Travelling Fellowship, EMBO/EMBL Symposia Series
2011 - Travelling Fellowship, FEBS/EMBO Youth Travel Fund
2008 – Erasmus Scholarship

Group members

 

Leader

Stefan Bresson, PhD

Leader

Viruses are remarkably simple creatures, with some consisting of little more than an RNA genome packaged together with viral proteins. Despite this simplicity, viruses have evolved sophisticated strategies to hijack cellular machinery. After gaining entry to a suitable host cell, the virus commandeers the cell’s protein production machinery and uses it to build new virus proteins. At the same time, the virus suppresses the production of cellular proteins in an effort to prevent the host cell from mounting a defense. By studying how viruses manipulate host resources and machinery, we can identify potential weak points in the virus’s replication cycle. In the future, we can use this knowledge to develop better treatment options.

Research Summary

Research in our laboratory is focused on two main areas of interest:

1. How do RNA viruses hijack the cell’s protein synthesis machinery?
   Viruses employ a number of mechanisms to ensure their RNA is efficiently translated by host ribosomes. One common strategy involves the use of internal ribosome entry sites (IRESs); these elements can directly recruit host ribosomes to viral RNA, bypassing conventional cap-dependent translation initiation. However, in order to function effectively, IRESs require the assistance of various cellular RNA-binding proteins. These accessory factors, termed ITAFs (IRES trans-acting factors), help the IRES fold into its final, active conformation. Because ITAFs are specifically required for viral but not host translation, they could potentially serve as ideal antiviral drug targets. We aim to identify and characterize factors involved in IRES-dependent translation in picornaviruses, a diverse family of RNA viruses which includes numerous human pathogens. In parallel, we are also investigating how cellular translation is reprogrammed during the course of picornavirus infection.
   
   
2. What is the relationship between viral replication and cellular RNA decay factors?
   Viral infection drives a continuous arms race between virus and host; viruses develop new strategies to exploit cellular pathways, while the host counters with new mechanisms to thwart the invader. A key component in the host’s arsenal is the cytoplasmic RNA decay machinery, which provides the first line of defense against invading viruses with RNA genomes. In response, RNA viruses have evolved various countermeasures to disable cellular decay pathways. Flaviviruses, for example, encode a specialized RNA structure which inactivates and sequesters the 5′ to 3′ cytoplasmic exonuclease Xrn1. Other RNA viruses have analogous mechanisms for suppressing cytoplasmic decay, but coronavirus may be an exception. Genome-wide CRISPR screens and small molecule studies have unexpectedly identified several cytoplasmic RNA decay factors as proviral factors which facilitate viral replication. We aim to understand the mechanistic basis for this counterintuitive observation. Do cytoplasmic RNA decay factors remove RNAs that would otherwise provoke an antiviral response, thereby allowing the virus to escape detection? Alternatively, do RNA decay factors directly regulate viral and/or cellular gene expression? We are addressing these questions using high

Scientific Impact

Our research investigates the host cellular factors that RNA viruses exploit to replicate efficiently. By identifying these critical interactions, we hope to inform the development of new antiviral therapies.

Future Goals

We aim to understand how RNA viruses coordinate the production, processing, and regulation of their proteins within host cells — especially in the absence of traditional transcriptional control mechanisms. In parallel, we are investigating the interplay between RNA viruses and the cellular RNA degradation machinery.
 

About the lab

Stefan Bresson, PhD Correspondence address: Laboratory of RNA Viruses 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.

DEGREES

2015 – PhD in Biological Chemistry, University of Texas, Southwestern Medical Center, Dallas, USA
2009 – BSc in Molecular and Cell Biology, University of Texas at Austin, USA

PROFESSIONAL EXPERIENCE

2025-present – Head of Laboratory of RNA Viruses, International Institute of Molecular and Cell Biology in Warsaw, Poland
2015-2024 – Postdoctoral research with Prof. David Tollervey at the University of Edinburgh, UK
2010-2014 – PhD research with Prof. Nicholas Conrad at the University of Texas, Southwestern Medical Center, Dallas, USA
2008-2009 – Undergraduate researcher with Prof. Arlen Johnson at the University of Texas at Austin, USA

HONORS, PRIZES AND AWARDS

2025 – SONATA BIS 14, National Science Center
2025 - VirHoX Hop-on, Horizon Europe

Group members

Lab Leader:
Stefan Bresson, PhD

Postdoctoral researcher:
Maja Cieplak-Rotowska, PhD
Martin Requena, PhD

Laboratory Support Specialist:
Marta Jankowska, MSc

PhD students:
Khashpatika Ganesh, MSc
Swagatika Moharana, MSc

MSc student:
Martyna Roszko, BSc

Undergraduate:
Paraskevi Terzidou, ERASMUS+ student