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LABORATORY OF PROTEIN METABOLISM

Pokrzywa Lab logo

Wojciech Pokrzywa Lab

Who we are

We are a research lab located at the International Institute of Molecular and Cell Biology in Warsaw, one of the best research institutions in Poland.

We focus on mechanisms of protein metabolism - maintenance of the balance between the synthesis and degradation of proteins. We explore the regulation of translation, the ubiquitin-proteasome system, the chaperone network, and muscular exophers in proteostasis. However, we are sometimes intrigued by topics outside this list.

In Pokrzywa lab, we use a combination of biochemical, microscopic, molecular genetics, and bioinformatics techniques, supported by mammalian cell assays and the nematode C. elegans.

Research

Scheme of impact of cold on transcriptome and proteome
Cellular adaptation to cold

To counteract cold, organisms developed various responses, ranging from cold avoidance to adaptation. The latter strategy is used by hibernating animals, which, in extreme cases, can survive subzero temperatures for many days.
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. 

Scheme of muscular exopheresis
Regulation of exophergenesis

We showed that body wall muscles of C. elegans release exophers that can transport muscle-synthesized yolk proteins to support offspring development, increasing their odds of development and survival (Turek et al., 2021). However, we do not know how exophergenesis is regulated in response to external factors that impact animal development and reproduction.
C. elegans exhibits a range of social behaviors that are primarily governed by various pheromones. Pheromone and sensory neuron-based communication between animals modulates animal growth, generation time, and maternal provisioning, and we explore this system to determine the influence of social cues on exophergenesis. We recently found that exophers are differentially modulated by sex-specific ascarosides (i.e., pheromones that are used in communication between individuals) and that sensory neurons and the G-protein coupled receptor 173 regulate exophergenesis in response to environmental stimuli and pheromones (Banasiak et al., 2023). We also found that AQR/PQR/URX neurons, which are directly exposed to pseudocoelomic fluid and monitor the worm's body interior, restrict muscle exopher production.
To our knowledge, our newest study is the first to report how animal communication influences somatic extracellular vesicle production. We currently explore this model to identify the molecular mechanism of exophergenesis at the muscle level.

Schema of E3 ligase complex
E3 ligase complexes in health, disease and aging

The cooperation of E3 ligases (i.e., essential components of the ubiquitin-proteasome system that recognize damaged and unwanted proteins) can lead to the formation of alternative ubiquitination structures that aid in directing substrate specificity. CHIP and its worm ortholog CHN-1 are E3 ubiquitin ligases that link the chaperone system with the UPS. CHN-1 can cooperate with UFD-2, another E3 ligase, to accelerate ubiquitin chain formation; however, the basis for the high processivity of this E3 set has remained obscure.
We study the molecular mechanism and function of the CHN-1–UFD-2 complex in C. elegans. Our data show that UFD-2 binding promotes cooperation between CHN-1 and ubiquitin-conjugating E2 enzymes by stabilizing the CHN-1 U-box dimer. However, the HSP70/HSP-1 chaperone outcompetes UFD-2 for CHN-1 binding, thereby promoting a shift to the autoinhibited CHN-1 state by acting on a conserved residue in its U-box domain. The interaction with UFD-2 enables CHN-1 to efficiently ubiquitination and regulate S-adenosylhomocysteinase, a key enzyme in the S-adenosylmethionine regeneration cycle, which is essential for S-adenosylmethionine-dependent methylation. Our results define the molecular mechanism that underlies the synergistic cooperation of CHN-1 and UFD-2 in substrate ubiquitination. We currently investigate the physiological role of CHN-1-UFD-2 tandem in disease and aging.

Scheme of a lysine desert protein
Regulation of lysine-deficient proteome through non-canonical ubiquitination

The ubiquitin-proteasome system (UPS) is a major pathway that removes damaged and unwanted proteins. The proteasome recognizes ubiquitinated proteins – tagged with a small protein named ubiquitin and degrades them. Ubiquitin is mainly attached to lysine residues of the protein destined for degradation in a process termed ubiquitination. However, the UPS must effectively eliminate only undesirable proteins while leaving the functional and essential ones intact. An intuitive mechanism of a proteome susceptible to premature ubiquitination is to avoid lysines in critical domains or entire sequences, potentially leaving a few whose ubiquitination can be precisely controlled.
An extensive lysine-less region (i.e., lysine desert) in the yeast E3 ligase Slx5 was shown to counteract its ubiquitin-dependent turnover. We conducted bioinformatic screens among prokaryotes and eukaryotes to describe the scope and conservation of this phenomenon (Szulc et al., 2023). We found that lysine deserts are widespread among bacteria using pupylation-dependent proteasomal degradation, an analog of the UPS. In eukaryotes, lysine deserts appear with increasing organismal complexity, and the most evolutionarily conserved are enriched in UPS members. Using VHL and SOCS1 E3 ligases, which elongated their lysine desert during the course of evolution, we established that they are non-lysine ubiquitinated, which does not influence their stability and can be subjected to proteasome turnover regardless of ubiquitination. Our data suggest that a combination of non-lysine ubiquitination and ubiquitin-independent degradation may control the function and fate of the lysine-deficient proteome because the presence of lysine deserts does not correlate with half-life. We currently study the regulation of other lysine-depleted receptors of cullin-RING ligases, as well as we aim to decipher the role of lysine-less regions in protein turnover and to develop an analytical method to catalog and study the role of non-lysine ubiquitination by applying biochemical and proteomic approaches and deep learning.

Scheme of myosin assembly
DEGRONOPEDIA: a web server for the proteome-wide inspection of degrons

A degradation-targeting degron comprises a nearby ubiquitin-modified residue and an intrinsically disordered region that interacts with the proteasome. Degron signaling has been studied over recent decades, but there are no resources for the systematic screening of degron sites to facilitate studies on their biological significance, such as targeted protein degradation approaches.
To bridge this gap, we are developing DEGRONOPEDIA (degronopedia.com), a web server that allows the exploration of degron motifs in proteomes of several model organisms and maps these data to lysine, cysteine, threonine, and serine residues that can undergo ubiquitination and to intrinsically disordered regions that are proximal to them, both in sequence and structure. The server provides the evolutionary context of degrons and reports post-translational modifications and pathogenic mutations within the degron and its flanking regions as these can modulate the degron’s accessibility. DEGRONOPEDIA allows analyses of custom sequences/structures to examine them for degron motifs. We also implemented machine learning to predict the stability of protein N- and C -termini, facilitating the identification of substrates of N-/C-degron pathways. This project also concerns the experimental validation of predicted degrons in a cellular context. We are continually implementing new features of DEGRONOPEDIA based on feedback from users and expanding the database of degron motifs because our tool aims to stimulate research on degron signaling. 

News

October 2024 | DEGRADATOR receives an award

DEGRADATOR ad

DEGRADATOR, our educational computer game on protein degradation, has been awarded 3rd place in the fully developed games category at the 12th International Educational Games Competition, part of ECGBL 2024 at Aarhus University in Denmark! This innovative game blends molecular biology with engaging gameplay, making complex scientific concepts accessible and entertaining. Developed with support from the Polish State Budget under the Ministry of Education and Science’s Social Responsibility of Science program, DEGRADATOR highlights the value of interactive learning in advancing scientific literacy.

October 2024 | New article published

Microscopic images of C. elegans body

We have released our new study in the Journal of Biological Chemistry on the critical role of HSP-1 heat shock protein in regulating the ubiquitin ligase CHN-1/CHIP to preserve germline integrity under stress conditions in C. elegans. Our research demonstrates that HSP-1 binding decreases CHN-1 activity, preventing excessive degradation of essential reproductive proteins during heat stress. These findings highlight the importance of the HSP-1–CHN-1 interaction in maintaining fertility under stress and may offer insights into similar proteostasis mechanisms in humans.

September 2024 | Our presence
at EMBO conference

Natalia presenting

We are pleased to share that Natalia, our Ph.D. student, presented our research on lysine deserts at the EMBO Workshop “Ubiquitin and Ubiquitin-like Proteins in Health and Disease” in Cavtat-Dubrovnik. The meeting was filled with exciting new findings in the ubiquitin field, and we feel honored to have had the opportunity to present our work alongside such cutting-edge research.

September 2024 | Our presence
at PACS2 conference

Wojciech presenting

We are very grateful to have been invited to the "UNLOCKING HOPE for the Ultra-Rare" conference at the Medical University of Warsaw, organized by the PACS2 Research Foundation. Our P.I., Wojciech, shared our findings on a previously uncharacterized neurodevelopmental disorder caused by an ultra-rare mutation in the FEM1C ubiquitin ligase. We believe this event will be remembered as a groundbreaking moment for the rare disease patient environment in Poland, as the Polish PACS2 community united scientists from around the world in just two years to explore potential therapies for PACS2 dysfunction. We are keeping our fingers crossed for these efforts to lead to a breakthrough!

August 2024 | New article
published

OptIMMuS visualization

In collaboration with CECAD Cologne, we have published new paper in Nature Communications introducing OptIMMuS, an optogenetic model of C. elegans for studying muscle proteostasis under mechanical stress. Our work identifies key regulators, including the TRIM E3 ligase NHL-1, which interacts with the chaperone UNC-45 to control myosin levels during muscle contraction. Our model offers a new approach to exploring muscle-specific proteostasis with potential therapeutic relevance.

July 2024 | New article
published

C. elegans visualization

We have published new article in PLOS Genetics revealing that floxuridine (FUdR), an anti-cancer drug, enhances proteasome resilience in C. elegans. Our study shows that FUdR supports the worms’ lifespan and ability to survive in cold environments (4°C) by activating a unique detoxification pathway, even when proteasome function is compromised. Our findings suggest novel strategies for boosting cellular resilience to stress and aging.

June 2024 | Our presence
at Rare Disease Congress

Presentation's title slide

We were delighted to present again, this time online, at the 3rd Congress of the Jesteśmy Pod Ścianą Foundation, "Connecting Worlds and People." Our P.I., Wojciech, shared our findings on a rare disease related to protein glycosylation malfunctions involving one of the genes of the PIG family. We are optimistic that our research will lead to meaningful outcomes for patients.

June 2024 | Our presence at the ubiquitin meeting

Natalia's talk

We are thrilled to announce that Natalia, our Ph.D. student, presented our research on lysine deserts at the 2nd Severo Ochoa Conference entitled "Ligating the Ubiquitin Family: Physiology, Disease, and Future Directions" in Bilbao. The feedback on our findings was overwhelmingly positive, and we look forward to continuing our contributions to the dynamic ubiquitin field.

April 2024 | Launch of our DEGRADATOR game

DEGRADATOR logo

We are excited to introduce DEGRADATOR, an engaging educational game designed to popularize and elucidate the complexities of the ubiquitin-proteasome system and PROTACs. Aimed at kids 12 and up but enjoyable for all ages, DEGRADATOR offers 10 dynamic levels where players can immerse themselves in the world of protein degradation.

The game is now available for download on Google Play or can be played directly in the web browser at degradator-game.com.

Publications

2024

HSP70 inhibits CHIP E3 ligase activity to maintain germline function in Caenorhabditis elegans
Thapa, P., Chikale, R.V.†, Szulc, N.A.†, Pandrea, M-T., Sztyler, A., Jaggi, K., Niklewicz, M., Serwa, R. A., Hoppe, T., & Pokrzywa, W.*
Journal of Biological Chemistry
doi: 10.1016/j.jbc.2024.107864

Optogenetic induction of mechanical muscle stress identifies myosin regulatory ubiquitin ligase NHL-1 in C. elegans
Kutzner, C.E., Bauer, K.C., Lackmann, JW., Acton R.J., Sarkar A., Pokrzywa W. & Hoppe T.
Nature Communications
doi: 10.1038/s41467-024-51069-3

Floxuridine supports UPS independent of germline signaling and proteostasis regulators via involvement of detoxification in C. elegans
Dubey, A. A., Sarkar, A., Milcz, K., Szulc, N. A., Thapa, P., Piechota, M., Serwa, R. A., & Pokrzywa, W.*
PLOS Genetics
doi: 10.1371/journal.pgen.1011371

SARS-CoV-2 inhibitory potential of fish oil-derived 2-pyrone compounds by acquiring linoleic acid binding site on the spike protein
Duragkar, N., Chikhale, R., Piechota, M., Danta, C. C., Gandhale, P., Itankar, P., Chikhale, S., Gurav, N., Khan, M. S., Pokrzywa, W., Thapa, P., Bryce, R., & Gurav, S.*
International Journal of Biological Macromolecules
doi: 10.1016/j.ijbiomac.2024.133634

DEGRONOPEDIA: a web server for proteome-wide inspection of degrons
Szulc N.A.*, Stefaniak F., Piechota M., Soszyńska A., Piórkowska G., Cappannini A., Bujnicki J.M., Maniaci C., & Pokrzywa W.*
Nucleic Acids Research
doi: 10.1093/nar/gkae238

Pheromone-based communication influences the production of somatic extracellular vesicles in C. elegans
Szczepańska A† ., Olek K.† , Kołodziejska K., Yu J., Tudu Ibrahim A., Adamkiewicz L., Schroeder F.C., Pokrzywa W.* & Turek M.*
Nature Communications
doi: 10.1038/s41467-024-47016-x

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bolded - member of t he Pokrzywa lab
* corresponding author
† equal contribution

2023

SAM, SAH and C. elegans longevity: insights from a partial AHCY deficiency model
Thapa P, Olek K., Kowalska A., Serwa R.A, & Pokrzywa W.*
npj Aging
doi: 10.1038/s41514-023-00125-1 

Lysine deserts and cullin-RING ligase receptors: Navigating untrodden paths in proteostasis
Szulc N.A.*, Piechota M., Biriczova L., Thapa P., & Pokrzywa W.*
iScience
doi: 10.1016/j.isci.2023.1083 

Sterility-Independent Enhancement of Proteasome Function via Floxuridine-Triggered Detoxification in C. elegans
Dubey A.A., Szulc N.A., Piechota M., Serwa R.A. & Pokrzywa W.*
bioRxiv
doi: 10.1101/2023.11.11.566706 

Structural Interaction Fingerprints and Machine Learning for predicting and explaining binding of small molecule ligands to RNA
Szulc N.A.*, Mackiewicz Z., Bujnicki J.M.* & Stefaniak F.*
Briefings in Bioinformatics
doi: 10.1093/bib/bbad187

In silico analysis of the profilaggrin sequence indicates alterations in the stability, degradation route, and intracellular protein fate in filaggrin null mutation carriers
Paul A.A.†, Szulc N.A.†, Kobiela A., Brown S.J., Pokrzywa W.* & Owsiak-Gutowska D.*
Frontiers in Molecular Biosciences
doi: 10.3389/fmolb.2023.1105678

SAH and C. elegans Longevity: Insights from an AHCY Deficiency Model
Thapa P., Banasiak K., Serwa R. & Pokrzywa W.*
Research Square
doi: 10.21203/rs.3.rs-2855835/v1 

Impaired iron recycling from erythrocytes is an early hallmark of aging
Slusarczyk P., Mandal P.K., Zurawska, G. Niklewicz M., Chouhan K., Mahadeva R., Jończy A., Macias M., Szybinska A., Cybulska-Lubak M., Krawczyk O., Herman S., Mikula M., Serwa R., Lenartowicz M., Pokrzywa W. & Mleczko-Sanecka K.
eLife
doi: 10.7554/eLife.79196 

Lysine-deficient proteome can be regulated through non-canonical ubiquitination and ubiquitin-independent proteasomal degradation
Szulc N.A.*, Piechota M., Thapa P., & Pokrzywa W.*
bioRxiv
doi: 10.1101/2023.01.18.524605 

Structural Interaction Fingerprints and Machine Learning for predicting and explaining binding of small molecule ligands to RNA
Szulc N.A.*, Mackiewicz Z., Bujnicki J.M.* & Stefaniak F.*
bioRxiv
doi: 10.1101/2023.01.11.523582 

Preparation of Caenorhabditis elegans for Scoring of Muscle-derived Exophers
Banasiak K.*, Turek M.* & Pokrzywa W.*
Bio-protocol
doi: 10.21769/BioProtoc.4586

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bolded - member of the Pokrzywa lab
* corresponding author
† equal contribution

2022

Pheromone-dependent olfaction bidirectionally regulates muscle extracellular vesicles formation
Banasiak K., Szczepańska A., Kołodziejska K., Tudu Ibrahim A., Pokrzywa W.* & Turek M.*
bioRxiv
doi: 10.1101/2022.12.22.521669 

In silico analysis of the profilaggrin sequence indicates alterations in the stability, degradation route, and intracellular protein fate in filaggrin null mutation carriers
Paul A.A.†, Szulc N.A.†, Kobiela A., Brown S.J., Pokrzywa W.* & Owsiak-Gutowska D.*
Research Square
doi: 10.21203/rs.3.rs-2302890/v1 

A novel de novo FEM1C variant is linked to neurodevelopmental disorder with absent speech, pyramidal signs, and limb ataxia
Dubey A.A.†, Krygier M.†, Szulc N.A.†, Rutkowska K., Kosinska J., Pollak A., Rydzanicz M., Kmiec T., Mazurkiewicz-Beldzinska M., Pokrzywa W.* & Ploski R.*
Human Molecular Genetics
doi: 10.1093/hmg/ddac276 

A dimer-monomer switch controls CHIP-dependent substrate ubiquitylation and processing
Balaji V., Müller L., Lorenz R., Kevei E., Zhang W.H., Santiago U., Gebauer J., Llamas E., Vilchez D., Camacho C.J., Pokrzywa W. & Hoppe T.
Molecular Cell
doi: 10.1016/j.molcel.2022.08.003 

Ferritin-mediated iron detoxification promotes hypothermia survival in Caenorhabditis elegans and murine neurons
Pekec T., Lewandowski J., Komur A.A., Sobańska D., Guo Y., Świtońska-Kurkowska K., Małecki J.M., Dubey A.A., Pokrzywa W, Frankowski M., Figiel M. & Ciosk R.
Nature Communications
doi: 10.1038/s41467-022-32500-z 

A heterotypic assembly mechanism regulates CHIP E3 ligase activity
Das, A., Thapa, P., Santiago, U., Shanmugam, N., Banasiak, K., Dabrowska, K., Nolte, H., Szulc, N.A., Gathungu, R. M., Cysewski, D., Krueger, M., Dadlez, M., Nowotny, M., Camacho, C. J., Hoppe, T., & Pokrzywa, W.*
EMBO Journal
doi: 10.15252/embj.2021109566 

fingeRNAt - a novel tool for high-throughput analysis of nucleic acid-ligand interactions
Szulc, N.A.*, Mackiewicz, Z., Bujnicki, J.M.*, & Stefaniak F.*
PLOS Computational Biology
doi: 10.1371/journal.pcbi.1009783 

DEGRONOPEDIA - a web server for proteome-wide inspection of degrons
Szulc N.A.*, Stefaniak F., Piechota M., Cappannini A., Bujnicki J.M. & Pokrzywa W.*
bioRxiv
doi: 10.1101/2022.05.19.492622 

CHIP ubiquitin ligase is involved in the nucleolar stress management
Piechota M.*, Biriczova L.†, Kowalski K.†, Szulc N.A. & Pokrzywa W.*
bioRxiv
doi: 10.1101/2022.05.17.492288

A novel de novo FEM1C variant is linked to neurodevelopmental disorder with absent speech, pyramidal signs, and limb ataxia
Dubey A.A.†, Krygier M.†, Szulc N.A.†, Rutkowska K., Kosinska J., Pollak A., Rydzanicz M., Kmiec T., Mazurkiewicz-Beldzinska M., Pokrzywa W.* & Ploski R.*
bioRxiv
doi: 10.1101/2022.04.24.489208

Impaired iron recycling from erythrocytes is an early iron-dependent hallmark of aging
Mandal, P. K., Slusarczyk P., Zurawska G., Cybulska M., Krawczyk O., Mikula M., Herman S., Lenartowicz M., Serwa R., Pokrzywa W., & Mleczko-Sanecka K.
bioRxiv
doi: 10.1101/2022.01.16.476518

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bolded - member of the Pokrzywa lab
* corresponding author
† equal contribution

2021

fingeRNAt - a novel tool for high-throughput analysis of nucleic acid-ligand interactions
Szulc, N.A.*, Mackiewicz, Z., Bujnicki, J.M.*, & Stefaniak F.*
bioRxiv
doi: 10.1101/2021.12.23.474073 

Heterotypic assembly mechanism regulates CHIP E3 ligase activity
Das, A., Thapa, P., Santiago, U., Shanmugam, N., Banasiak, K., Dabrowska, K., Nolte, H., Szulc, N.A., Gathungu, R. M., Cysewski, D., Krueger, M., Dadlez, M., Nowotny, M., Camacho, C. J., Hoppe, T., & Pokrzywa, W.*
bioRxiv
doi: 10.1101/2021.08.20.457118 

Muscle-derived exophers promote reproductive fitness
Turek, M., Banasiak, K., Piechota, M., Shanmugam, N., Macias, M., Śliwińska, M. A., Niklewicz, M., Kowalski, K., Nowak, N., Chacinska, A., & Pokrzywa, W.*
EMBO reports
doi: 10.15252/embr.202052071 

Maintaining proteostasis under mechanical stress
Höhfeld, J., Benzing, T., Bloch, W., Fürst, D.O., Gehlert, S., Hesse, M., Hoffmann, B., Hoppe, T., Huesgen, P.F., Köhn, M., Kolanus, W., Merkel, R., Niessen, C. M., Pokrzywa, W., Rinschen, M.M., Wachten, D., & Warscheid, B.
EMBO reports
doi: 10.15252/embr.202152507 

The dose-dependent pleiotropic effects of the UBB+1 ubiquitin mutant
Banasiak, K., Szulc, N.A., & Pokrzywa, W.*
Frontiers in Molecular Biosciences
doi: 10.3389/fmolb.2021.650730

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bolded - member of the Pokrzywa lab
* corresponding author

2020

The ubiquitin-conjugating enzyme UBE2K determines neurogenic potential through histone H3 in human embryonic stem cells
Fatima, A., Irmak, D., Noormohammadi, A., Rinschen, M.M., Das, A., Leidecker, O., Schindler, C., Sánchez-Gaya, V., Wagle, P., Pokrzywa, W., Hoppe, T., Rada-Iglesias, A., & Vilchez, D.
Communications Biology
doi: 10.1038/s42003-020-0984-3 

Ubiquitin signaling regulates RNA biogenesis, processing, and metabolism
Thapa, P., Shanmugam, N., & Pokrzywa, W.*
BioEssays
doi: 10.1002/bies.201900171

CHIP ubiquitylates NOXA and induces its lysosomal degradation in response to DNA damage
Albert, M.-C., Brinkmann, K., Pokrzywa, W., Günther, S. D., Krönke, M., Hoppe, T., & Kashkar, H.
Cell Death & Disease
doi: 10.1038/s41419-020-02923-x 

Bioshell 3.0: Library for processing structural biology data
Macnar, J.M., Szulc, N.A., Kryś, J.D., Badaczewska-Dawid, A.E., & Gront, D.
Biomolecules
doi: 10.3390/biom10030461 

Pathogenic variants in the myosin chaperone UNC-45B cause progressive myopathy with eccentric cores
Donkervoort, S., Kutzner, C. E., Hu, Y., Lornage, X., Rendu, J., Stojkovic, T., Baets, J., Neuhaus, S.B., Tanboon, J., Maroofian, R., Bolduc, V., Mroczek, M., Conijn, S., Kuntz, N. L., Töpf, A., Monges, S., Lubieniecki, F., McCarty, R. M., Chao, K. R., Governali, S., Böhm, J., Boonyapisit, K., Malfatti, E., Sangruchi, T., Horkayne-Szakaly, I., Hedberg-Oldfors, C., Efthymiou, S., Noguchi, S., Djeddi, S., Iida, A., di Rosa, G., Fiorillo, C., Salpietro, V., Darin, N., Faure, J., Houlden, H., Oldfors, A., Nishino, I., de Ridder, W., Straub, V., Pokrzywa, W., Laporte, J., Foley, R., Romero, N.B., Ottenheijm, C., Hoppe, T., & Bönnemann, C.G.
The American Journal of Human Genetics
doi: 10.1016/j.ajhg.2020.11.002

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bolded - member of the Pokrzywa lab
* corresponding author

2018

Ubiquitylation pathways in insulin signaling and organismal homeostasis
Balaji, V.†, Pokrzywa, W.†, & Hoppe, T.
BioEssays
doi: 10.1002/bies.201700223 

The ubiquitin ligase UBR5 suppresses proteostasis collapse in pluripotent stem cells from Huntington’s disease patients
Koyuncu, S., Saez, I., Lee, H. J., Gutierrez-Garcia, R., Pokrzywa, W., Fatima, A., Hoppe, T., & Vilchez, D.
Nature Communications
doi: 10.1038/s41467-018-05320-3

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bolded - member of the Pokrzywa lab
† equal contribution

2017

Chaperone-directed ubiquitylation maintains proteostasis at the expense of longevity
Pokrzywa, W., Lorenz, R., & Hoppe, T.
Worm
doi: 10.1080/21624054.2017.137140 

CHIPped balance of proteostasis and longevity
Pokrzywa, W., & Hoppe, T.
Oncotarget
doi: 10.18632/oncotarget.22101 

Repair or destruction - an intimate liaison between ubiquitin ligases and molecular chaperones in proteostasis
Kevei, É.†, Pokrzywa, W.†, & Hoppe, T.
FEBS Letters
doi: 10.1002/1873-3468.12750

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bolded - member of the Pokrzywa lab
† equal contribution

Game

In addition to conducting scientific research, our lab is also a computer games studio after hours :)

DEGRADATOR is an innovative 2D game blending education with entertainment, inviting players to take on the role of an enzyme involved in breaking down proteins in cells. Spanning ten levels, this game is the first to explore the process of protein degradation, a vital aspect of maintaining cellular health. The game also educates on cutting-edge PROTAC drug technology with quizzes and an in-game encyclopedia. Aimed at making complex science simple, DEGRADATOR is perfect for anyone looking to learn through play, offering insights into the world of molecular biology.

The game is available for download on Google Play or can be played directly in the web browser at degradator-game.com. 

Facilities

In the Pokrzywa lab, in addition to standard equipment and a coffee machine, we have several state-of-the-art research instruments for worms and proteins analysis, including:

WormLab® Imaging System

ScreenChip™ System

wMicroTracker

CherryTemp

ZEISS Axio Zoom.V16 Fluorescence Microscope

ÄKTA Go Protein Purification System

Funding

Logos of funding agencies
Open grants
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Closed grants
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Team

Principal Investigator

Photo of Dr. Wojciech Pokrzywa

Wojciech Pokrzywa, Ph.D., D.Sc.

ORCID, LinkedIn, X

During his Ph.D. studies at the Catholic University of Louvain, Belgium, Wojciech Pokrzywa investigated the function of the ubiquitin-proteasome system in regulating membrane protein localization in yeast. In 2009, he joined the laboratory of Prof. Thorsten Hoppe at the University of Cologne, Germany, where he studied the mechanisms of proteostasis during development and aging in C. elegans.
In mid-2017, he started his own research group in Warsaw focusing on the mechanisms of protein metabolism regulation.

Lab Members

POSTDOCTORAL RESEARCHERS

Małgorzata Piechota, Ph.D.
Anna Soszyńska, Ph.D. ✉

Laboratory Support Specialists 

Anna Grabowska, Ph.D. ✉
Marta Niklewicz, M.Sc.
Agnieszka Sztyler, M.Sc. ✉

Ph.D. STUDENTS

Pankaj Thapa, M.Sc. ✉
Natalia Szulc, M.Sc. ✉
Anwesha Sarkar, M.Sc. ✉
Karolina Milcz, M.Sc.
Lilla Biriczová, M.Sc.

MASTER'S STUDENTS

Gabriela Piórkowska, B.Sc.

Join Us

Are you interested in molecular mechanisms of proteostasis? Are you looking for a passionate group of scientists with an exceptionally friendly working atmosphere? Why not join the Pokrzywa lab?

We are always looking for highly motivated individuals eager to pursue research in our group. If you are interested in possible future opportunities, please send us your CV.

Contact

Laboratory Manager

Anna Grabowska, Ph.D.

Phone: +48 22 597 07 77
E-mail: agrabowska@iimcb.gov.pl

Principal Investigator

Wojciech Pokrzywa, Ph.D., D.Sc. 

Phone: +48 22 597 07 43
E-mail: wpokrzywa@iimcb.gov.pl

Address

Laboratory of Protein Metabolism

International Institute of Molecular and Cell Biology in Warsaw

4 Ks. Trojdena Street

02-109 Warsaw, Poland 

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