In 2017 our team started with the ambitious ReMedy project "Regenerative Mechanisms for Health” carried on within the International Research Agendas program of the Foundation for Polish Science.
In 2020 we became a cornerstone for the newly constituted institute of the Polish Academy of Sciences, created in partnership with University Medical Center Göttingen, Germany. The final and important step was a strategic agreement between PAS and the University of Warsaw concerning the joint project of setting up...
The International Institute of Molecular Mechanisms and Machines (IMol).
IMol has been established to conduct scientific research and provide training in the fields of biological, chemical, medical, biotechnological, bioinformatics, biophysical, pharmacological, and similar sciences, in the international environment conducive to collaborative efforts, research and development interactions with biotechnological industry, and wide dissemination of our results. We aim at the development of solutions that will help everyone on this planet live a safer life.
Since all the research groups in ReMedy project will be organized at IMol upon the transfer of ReMedy funding from the University of Warsaw, they constitute the core of future IMol staff.
INTERNATIONAL SCIENTIFIC COMMITTEE
The science research work of ReMedy is carried out under the guidance of the International Scientific Committee, consisting of respected scientists from prestigious universities:
Nobel Laureate, Massachusetts Institute of Technology, Cambridge, MA, USA
PROF. PHILLIP A. SHARP - CHAIR
Friedrich Miescher Institute for Biomedical Research, Switzerland
PROF. WITOLD FILIPOWICZ - VICE CHAIR
Wellcome Trust Centre for Mitochondrial Research, Newcastle, UK
PROF. ZOFIA CHRZANOWSKA - LIGHTOWLERS
The George S. Wise Faculty Of Life Science, Tel Aviv University, Israel
PROF. EHUD GAZIT
Max Planck Institute for Biophysical Chemistry, Germany
PROF. REINHARD LÜHRMANN
CEITEC – Central European Institute of Technology, Czech Republic
PROF. MARY ANNE
Cellular Biochemistry, University Medical Center Göttingen, Germany
PROF. PETER REHLING
Department of Neuro and Sensory Physiology, University Medical Center Göttingen, Germany
PROF. SILVIO RIZZOLI
PROF. AGNIESZKA CHACIŃSKA
Laboratory of Mitochondrial Biogenesis
Mitochondria play a key role in metabolism and regulatory processes within a cell. Thus, the formation of mitochondria is essential for cellular function of every being in the eukaryotic kingdom, from unicellular organisms to mammals. Mitochondria comprise 1000-1500 cellular proteins, which are synthesized outside of the mitochondria in the cytosol.
The biogenesis of mitochondria relies on the efficient import, sorting, and maturation of proteins, all governed by conserved protein translocases and other complex biological machinery.
Our research explores novel and exciting links between protein transport mechanisms and mitochondrial protein homeostasis. We postulate the presence of unique mechanisms involved in protein biogenesis that involve crosstalk between the cytosol and mitochondrial compartments.
Our goal is to better understand the complex and dynamic processes involved in the formation of functional organelles, as well as the maintenance of cellular protein homeostasis and its failures, which result in pathology.
PROF. MAGDA KONARSKA
Laboratory of RNA Biology
We use the yeast S. cerevisiae spliceosome as a model of a complex molecular machine; we want to understand the details of its architecture and function.
Our goal is to understand the complex set of substrate - spliceosome interactions during assembly and catalysis, which affect the positioning of reactive groups at the active site.
Our mechanistic studies in yeast will help us to understand the molecular interactions that influence splicing fidelity and alternative splicing in metazoan systems. The spliceosomal catalytic center undergoes dynamic changes during the catalytic phase of splicing; changes of relative stabilities of competing conformations at the catalytic center affect splicing catalysis, altering splicing fidelity and thus affecting the selection of splice site sequences for catalysis. These findings have implications for alternative splicing, common to most Eukaryotes.
We test new models of snRNA:snRNA interactions at the catalytic center implicated in the function of the catalytic triplex and positioning of the branch site.
We also study spliceosomal factors involved in the substrate positioning for catalysis, in particular, those containing disordered protein domains penetrating the catalytic center.
Another project investigates exon sequences that compensate for the defects of the intron 5’SS. Isolated yeast exon motifs are similar to metazoan exon enhancers; this striking sequence similarity suggests common underlying mechanisms of action. We hypothesize that yeast exon motifs represent substrate binding sites recognized by the spliceosome; we study the molecular mechanisms underlying their function.
PIOTR SZWEDZIAK, PHD
Laboratory of Structural Cell Biology
The last few years have seen dramatic developments in the field of electron cryomicroscopy (cryoEM). This technique allows imaging of biological material at multiple scales, from purified macromolecules to whole cells. Electron cryotomography (cryoET) is a cryoEM modality that resolves unique structures in situ, in a native state, in three dimensions and at the macromolecular resolution range, enabling structural studies in intact, frozen-hydrated cells.
In our research we are interested in utilisng a multiscale approach, combining imaging across scales (structural biology and cell biology approaches bridged by cryoET) with biochemistry to obtain a profound understanding of cellular organisation and architecture at the molecular level. Our group routinely employs cryoET imaging of in vitro reconstituted systems, prokaryotic cells as well as micromachined eukaryotic cells. Our biological focus is on membrane:protein interactions in health and disease.
For cryoEM data collection we have access to an in-house 200 kV Thermo Fisher Glacios electron cryomicroscope equipped with a Falcon 3EC direct electron detector and a phase plate run by our core facility, and regularly collect our data on a Thermo Fisher Titan Krios G3i equipped with a phase plate, BioQuantum energy filter and both K3 and Falcon3EC direct electron detectors that is located at the National Centre for Electron Cryomicroscopy in Kraków. To generate thin specimens of eukaryotic cells for cryoET we employ a dual beam FIB-SEM Zeiss Auriga 60 equipped with a Quorum PP3010 cryo transfer system.
ANNA MARUSIAK, PHD
Laboratory of Molecular OncoSignalling
The Laboratory of Molecular OncoSignalling is interested in cancer biology, cellular signalling during oncogenesis and the identification of novel targets for cancer therapies.
Signal transduction plays an important role in cancer development and protein kinases, which are the master regulators of signalling pathways, represent key targets in cancer treatment. Our group wants to understand how aberrant signalling in cancer cells contributes to cancer development, metastasis or therapy resistance, and how we can use that knowledge to design novel anticancer treatments.
In particular, we focus on investigating oncogenic signalling activated by MLK4 in breast cancer. MLK4 is a member of Mixed-Lineage Kinase family of serine/threonine kinases that are activated by environmental stress, cytokines and growth factors and play a role in a variety of cellular processes. The members of MLK family have been involved in the regulation of a wide range of disorders including cancer, inflammation, metabolic and neurobiological disorders. Our lab investigates MLK4 signalling in breast cancer, where MLK4 is highly upregulated and contributes to malignant progression. One of our projects is focused on understanding the role of MLK4 in the response to chemotherapy in breast cancer. Furthermore, we aim to develop and validate the potency and efficacy of first-in-class MLK4-targeting compounds. We are also interested in uncovering the importance of MLK4-dependent cross-talk signalling between components of tumour microenvironment and breast cancer cells.
In our studies we use human and mouse cancer cell lines and syngeneic as well as xenograft tumour models in mice. We also use 3D cell cultures, flow cytometry, mass spectrometry and various phenotypic assays including invasion and migration assays.
PIOTR GERLACH, PHD
Laboratory of Structural Biology of Virus-host Interactions
RNA viruses are a diverse group of serious pathogens. Broadening structural insight into their molecular repertoire, and particularly virus-host intracellular interactions, is critical for complete understanding of infection mechanisms. Host translation is one of the major sites of the virus-host battlefront. Being a center of cellular stress response pathways, it is often abused by viruses to produce viral proteins. Of particular interest is the fate of cytoplasmic RNA granules during viral infection, as these compartments serve as a depository of host mRNA, stalled translation initiation complexes, and auxiliary factors that viruses can rely on.
My lab will combine structural biology expertise (cryo-EM, cryo-ET, and X-ray crystallography) with an in vivo platform – mammalian cell cultures transfected with minimal replicon systems, mimicking viral transcription and replication inside the infected cell. We will use this platform as a test tube for various assays, including functional and localisation studies, identification of novel host factors involved in viral infection, and structural analysis. Knowledge acquired on the way will open new research avenues that may ultimately lead to design of innovative therapies and broad-spectrum antivirals.
KAROLINA SZCZEPANOWSKA, PHD
Laboratory of Metabolic Quality Control
Metabolism is firmly defined by the mitochondria. They dictate the bioenergetic capacity of our cells and provide us with critical metabolites. The bulk of cellular energy is generated by the elaborative molecular machines embedded inside the mitochondrial membranes, jointly known as the OXPHOS system. The everyday stress impacts the composition and functionality of OXPHOS, leading to its dysfunction. Consequently, compromised OXPHOS fitness has been implicated in a broad spectrum of disorders, including cancer, diabetes, obesity, ischemia-reperfusion injury, neurodegeneration, or aging.
What are the mechanisms that sculpture OXPHOS in response to challenges? Is there a way to repair it when injured by stress? We recently started to recognize that mitochondrial bioenergetics stays under the constant surveillance of dedicated proteostatic machinery. Yet, the exact mechanisms and responsible players remain mostly elusive.
Our research aims to dissect the mechanisms that mediate the quality control of OXPHOS exposed to disease-associated conditions and trace the molecular signals that steer its degradation. With the help of modern proteomics and advanced biochemical and molecular biology approaches, we discover the damage hot-spots in mammalian mitochondria and identify the factors responsible for their recognition and repair.
Our findings will help to understand how metabolic quality control contributes to the known cellular stress-responses. Furthermore, OXPHOS salvage can constitute an attractive target for novel therapies against a broad range of human diseases.
The International Institute of Molecular Mechanisms and Machines
Polish Academy of Sciences
Mechanizmów i Maszyn Molekularnych
Polskiej Akademii Nauk
PL 31 1130 1017 0020 1582 5520 0001
Bank Gospodarstwa Krajowego S.A.
Al. Jerozolimskie 7, 00-955 Warszawa, Poland
Kod BIC (SWIFT): GOSKPLPW