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.
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.
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.
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.
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.
We are pleased that our web server, DEGRONOPEDIA, has been published. DEGRONOPEDIA is designed to search for degrons, map them to nearby ubiquitination sites, and provide insights into degron conservation, post-translational modifications, and more. Our experimental validation of a predicted C-terminal destabilizing motif, coupled with the confirmation of a post-proteolytic degron in another case, exemplifies its practical application. DEGRONOPEDIA can be freely accessed at degronopedia.com.
We are excited to announce our collaborative publication with Dr. Michał Turek's group from the Institute of Biochemistry and Biophysics PAS, presenting our research on the regulation of muscle extracellular vesicles (exophers) in C. elegans by sex-specific pheromones and olfactory neurons. These discoveries, featured in the Editors' Highlights section of Nature Communications journal, not only advance our understanding of inter-tissue communication but also open new pathways for investigating how social interactions affect biological systems at a cellular level.
We had the pleasure of hosting a group of talented high school students in our lab. Our research assistant, Agnieszka, along with our postdoctoral researcher Anna, introduced them to the nematode C. elegans, a tiny worm that plays a key role in many research endeavors, including several of ours. Our goal was to ignite their curiosity and inspire them to explore careers in science.
Our P.I., Wojciech, along with Ph.D. students Natalia and Anwesha, had the opportunity to visit our collaborator, Prof. Rafał Ciosk and his team at the University of Oslo. The purpose of the visit was to review our joint research efforts under the GRIEG grant and to develop strategies for exploring new research avenues in the upcoming years.
Today, as part of the conference "CePT as a platform for the development of innovative biomedicine 2024" at the Warsaw Medical University, our PI Wojciech had the pleasure of presenting the results of our research on rare diseases, with a special focus on a neurological disease caused by a mutation in the FEM1C gene. He also presented our scientific plans for the future, which include using the nematode C. elegans as a model to search for new therapeutic interventions.
At the Polish Science Gala, our team, consisting of P.I. Wojciech, postdocs Abhishek Dubey and Małgorzata Piechota, and Ph.D. students Aniruddha Das, Katarzyna Olek, Natalia Szulc and Pankaj Thapa, had the honor of receiving the team award from the Minister of Science and Higher Education for outstanding scientific achievements. These include our study of the role of muscle exophors in enhancing progeny viability, the discovery of the cooperative function of the ubiquitin ligases CHIP and UFD-2 in enhancing their ubiquitination processivity, and the identification of a rare mutation in FEM1C, establishing a link between this gene and a new neurodevelopmental disorder in a patient.
This award is not only a prestigious honor, but also a strong incentive to persevere in our research efforts, fueling our determination to continue deciphering the mysteries of biology.
New avenues of research on cold resistance and molecular mechanisms of phosphatases in this area are opening up in our lab, as our P.I., Wojciech, has been awarded a four-year PRELUDIUM BIS grant from the National Science Centre entitled "Chilling resilience: Decoding Phosphatases in Cold Adaptation."
We look forward to sharing our findings and their implications, especially for human health!
We have published an article on the effects of S-adenosylhomocysteine (SAH), a key intermediate compound required for methylation, on the mechanisms of aging. We conducted our study using the C. elegans nematodes expressing a pathogenic variant of the AHCY gene, responsible for a rare disease that impairs methionine metabolism in humans. Our results suggest that the balance between SAH and S-adenosylmethionine (SAM) serves as a key factor shaping the lifespan of C. elegans.
We have published an article on the phenomenon of lysine deserts, in which protein sequences show extensive stretches completely devoid of lysines. Our study shows that lysine deserts arose early in evolution and occur in bacteria using pupylation, a process analogous to eukaryotic ubiquitination. Despite the protective role of lysine deserts against cullin-mediated ubiquitination for VHL and SOCS1 substrate receptors, our findings indicate that these receptors can still undergo ubiquitination at sites other than lysines.
We have released a preprint elucidating the capacity of floxuridine (FUdR), an anti-cancer pharmaceutical agent, to enhance proteasome resilience in C. elegans under conditions of inhibition or subunit deficits. This phenomenon contributes to the extension of lifespan and facilitates adaptation to cold environments. Furthermore, our investigation reveals the induction of a distinctive detoxification pathway by FUdR.
Our P.I. Wojciech and Ph.D. student Natalia were invited to participate in the 1st Polish Conference of Families with Protein Glycosylation (GPI-AP) Disorders at St. Anne's Mountain. During the event, they presented the possibilities of using the nematode C. elegans as a model organism in human disease studies and discussed with Parents and Patients on the current progress and prospects of rare disease research in Poland.
Our P.I. Wojciech and two Ph.D. students, Natalia and Anwesha, had the pleasure of attending a workshop on mechanical stress protection at the excellent CECAD institute in Cologne. The meeting allowed us to learn about the latest state-of-the-art research using the C. elegans nematode to better understand muscle functioning, and gave us the opportunity to share our own results and have fruitful scientific discussions.
Our laboratory, represented by our P.I., Wojciech, postdoc Abhishek and Ph.D. student Natalia, participated in the largest worm conference - the 24th International C. elegans Conference in Glasgow. We presented our research on the cold resistance effect that 5'-fluorodeoxyuridine (FUdR), an anticancer drug, exerts on C. elegans, as well as our results on an ultra-rare mutation in the FEM1C gene that causes a severe neurodevelopmental disorder. We were delighted that both of our posters received a lot of attention, and we look forward to the next meetings with the amazing C. elegans researchers at future conferences.
We were delighted to return to Cracow to participate in the 2nd Congress of the Jesteśmy Pod Ścianą Foundation "Rare Diseases - Views from Multiple Perspectives" at Jagiellonian University. Our P.I., Wojciech, and Ph.D. student, Natalia, presented how our research on an uncharacterized neurodevelopmental disorder caused by an ultra-rare mutation in the ubiquitin ligase FEM1C led to the diagnosis and shed some light on our current research focusing on deciphering the mechanism of the disease and developing a potential therapy. We hope that our other projects involving C. elegans and rare mutations will also yield valuable results for patients.
We are thrilled to share that Natalia, our Ph.D. student, presented our novel web server DEGRONOPEDIA at the "Proximity-inducing pharmacology: Targeted protein degradation and beyond" conference held at the IRB Barcelona - Institute for Research in Biomedicine. The response to the presentation was very positive, and we are excited to continue developing the tool.
You can access DEGRONOPEDIA at degronopedia.com.
Since S-adenosylhomocysteine (SAH) extends the lifespan of model organisms, we published a preprint describing our C. elegans model with elevated SAH levels generated by introducing a pathogenic mutation in the enzyme S-adenosylhomocysteine hydrolase (AHCY), which is associated with a rare autosomal recessive disorder of methionine metabolism. Our results demonstrate the potential of AHCY mutant worms as a tool to study AHCY-induced changes in SAH metabolism, as we showed that animals with AHCY mutation exhibited delayed aging accompanied by increased SAH levels.
Our sincerest congratulations to Katarzyna for an exceptional Ph.D. dissertation defense!
Katarzyna pushed the boundaries of our knowledge of muscular exophergenesis in C. elegans, and her efforts resulted in three articles in this field, one of which made it to the cover of EMBO Reports.
Furthermore, Katarzyna has co-authored two other publications on the ubiquitin-proteasome system and has shared her findings at various international conferences. Thank you Katarzyna for your valuable contribution to our projects and a common scientific journey!
Our lab hosted a group of high school students, to whom we introduced the fascinating C. elegans nematode, a tiny worm used as a model organism in many scientific studies, including our research on cellular adaptation to cold under the NCN GRIEG grant. We hope our presentation sparked their curiosity and inspired them to pursue a career in science.
Huge congratulations to Aniruddha on an outstanding Ph.D. dissertation defense!
Aniruddha's research on the synergistic cooperation between the ubiquitin ligases CHN-1 and UFD-2 resulted in a first-author article that landed on the cover of the EMBO Journal and formed the basis of his Ph.D. thesis. During doctoral studies, Aniruddha also presented his results at several international conferences and participated in other projects in the lab. Aniruddha will continue his research on the ubiquitin-proteasome system as a post-doc at the University of Texas at Austin in Prof. Andreas Matouschek's group.
Thanks to the EU-LIFE alliance of leading European life sciences research centers, our Ph.D. student Natalia gave an interview about the challenges of ensuring equal opportunities in science on the occasion of the International Day of Women and Girls in Science #WomenInSTEM.
In Pokrzywa lab, we fully support women and promote equality in all aspects.
On the occasion of the upcoming Rare Diseases Day, our Ph.D. student Natalia had the pleasure of presenting at the 6th National Scientific Conference on Rare Diseases in the 21st Century our research using the nematode C. elegans, in which we demonstrated that an ultra-rare mutation in the FEM1C gene causes neurodevelopmental disorders.
We hope that our study will contribute to the development of personalized therapies for patients with mutations in FEM1C.
Congratulations to our former master's student Konrad on his admission to the Ph.D. program. Konrad will conduct his doctoral research under the supervision of an ERC grantee, Dr. Adam Kłosin, at the Nencki Institute of Experimental Biology.
Konrad, we are very proud of you and wish you many successes and impactful discoveries!
Together with the group of Dr. Katarzyna Mleczko-Sanecka from our Institute, we have published an article showing that defects in red pulp macrophages - cells responsible for maintaining blood homeostasis - occur in early aging and disrupt iron turnover, contributing to anemia in elderly age.
We are very proud of this intra-institute collaboration and look forward to more thrilling joint research!
We have published a preprint describing our research on lysine-less proteins, so-called lysine deserts. We explored their prevalence, evolutionary conservation, and possible functional roles in prokaryotes and eukaryotes. In addition, using the example of lysine-free variants of VHL and SOCS1 proteins, we showed that they can undergo non-lysine ubiquitination and proteasome-dependent turnover which is independent of their ubiquitination.
We have just published a detailed protocol for quantifying muscle exophers in C. elegans. We hope that our resource will be useful to the scientific community in performing cutting-edge studies of these exciting extracellular vesicles.
Together with the group of Dr. Michał Turek from the Institute of Biochemistry and Biophysics, we released a preprint where we show how sex-specific pheromones and olfactory neurons regulate muscle extracellular vesicles (exophers) in C. elegans.
Our findings may imply the existence of an analogous mechanism regulating cardiomyocyte exophers, which contributes to the risk of cardiovascular disease in humans.
We congratulate our senior researcher Małgorzata on giving a talk about nucleolar proteostasis control at the Biomolecular condensates in biology and disease conference organized by the PhasAGE consortium in Brussels. We hope our data shed some light on the relation between CHIP ubiquitin ligase and nucleolus in cellular stress and phase separation.
We would like to congratulate our Ph.D. student Natalia on receiving the prestigious Fulbright Junior Research Award for the research stay at the Dana-Farber Cancer Institute in Boston.
Together with the group of Dr. Danuta Owsiak-Gutowska from the University of Gdańsk, we released a preprint where we shed some light on the degradation routes of filaggrin, an important protein in the pathogenesis of atopic dermatitis.
We show the involvement of the proteasome in filaggrin turnover and we describe filaggrin's potential degron sites and their effect on its mutated variants associated with the disease.
We are pleased that our collaboration with Prof. Rafał Płoski from the Medical University of Warsaw and Prof. Maria Mazurkiewicz-Bełdzińska from the Medical University of Gdańsk has resulted in a joint publication where we link an uncharacterized neurological disease with an ultra-rare mutation in FEM1C ubiquitin ligase.
In our article, we present the first evidence from an animal model, Caenorhabditis elegans nematode, suggesting that a mutation in the conserved FEM1C Asp126 position causes a neurodevelopmental disorder in humans.
We are very grateful for the invitation to the Rare Disease Congres in Cracow from the Jesteśmy Pod Ścianą Foundation, an NGO supporting patients with rare diseases. Our PI, Wojciech, and Ph.D. student, Natalia, presented our research on an uncharacterized neurodevelopmental disorder caused by an ultra-rare mutation in the FEM1C ubiquitin ligase and chorea-acanthocytosis. We hope that our research will contribute to a better understanding of the molecular mechanisms underlying these diseases.
Our PI, Wojciech, presented the poster about our study that hit the cover of the prestigious EMBO Journal at the 4th Interdisciplinary FNP Conference, organized by our funding agency - the Foundation for Polish Science. We are very grateful for the obtained funds which enabled our research and hope for more exciting discoveries.
Like last year, we were delighted to participate in the Science Festival in Warsaw, a well-recognized science popularization event in Poland. We unveiled some of the secrets of Caenorhabditis elegans and discussed its role in aging research. Students also had an opportunity to test their knowledge as we prepared a quiz with prizes.
We hope that we passed some of our fascination with this tiny creature to our listeners, and our lecture provided insight into the complex mechanisms of aging and the role of Caenorhabditis elegans in studying them.
Congratulations to our M.Sc. student Konrad for graduating with a Master’s degree in Biotechnology at the University of Warsaw!
Konrad wrote his thesis about the role of human CHIP ubiquitin ligase in nucleolar protein recovery after heat stress and co-authored our recent preprint. We are very proud of you and wish you many more successes!
We are delighted to announce that we were awarded the Social Responsibility of Science (Społeczna Odpowiedzialność Nauki) grant from the Ministry of Education and Science for developing an educational computer game about protein degradation processes in the cell.
As we believe that science should break out of its ivory tower and be widely accessible, the aim of the proposed computer game would be to explain how cells maintain protein homeostasis and why its disruption may lead to disease. Stay tuned!
Katarzyna, our Ph.D. student, gave a talk on our soon-to-be-released study on muscular exopheresis in Caenorhabditis elegans at the Basel Worm Meeting.
We are delighted that it gained a lot of attention of the worm community and cannot wait to publish it.
We would like to congratulate our Ph.D. student Natalia on receiving the prestigious 1st place in the contest organized by the Polish Bioinformatics Society for the best master’s thesis in bioinformatics defended in 2021 in Poland!
Our recently released story about the interplay of CHIP - UFD-2 ubiquitin ligases and our web server degronopedia.com have been presented by our PI Wojciech and Ph.D. student Natalia at the EMBO Workshop Ubiquitin and ubiquitin-like proteins in health and disease in Cavtat, Croatia.
We received a lot of questions and positive feedback and hope to reunite with the ubiquitin community at the next meeting.
More research on CHIP ubiquitin ligase, with our substantial contribution, has been published in Molecular Cell.
In this article, we show that CHIP exists as both a dimer, which promotes protein quality control, and a monomer, which plays a role in regulating aging. The conformation switch is controlled by CHIP auto-ubiquitination.
Our work, in collaboration with the group of Prof. Rafal Ciosk from the University of Oslo, has been published in Nature Communications.
We are very glad that we could participate in the study, showing that ferritin-mediated iron detoxification promotes the survival of C. elegans and mouse neurons in the cold.
The article can be found here.
Our article on the CHIP - UFD-2 ubiquitin ligase interplay and its role in regulating lipid metabolism has been featured on the cover of the EMBO Journal.
We imagine UFD-2 as a jazzman who promotes cooperation between CHIP and ubiquitin-coupling enzymes, doubling the activity of CHIP - a double bell saxophone releasing ubiquitin. Through this graphic, we also wanted to pay tribute to the famous Warsaw Jazz Jamboree, which we adore.
Our article can be found here.
Our new follow-up study on muscular exopheresis in Caenorhabditis elegans has been presented at the European Worm Meeting in Vienna.
Katarzyna, our Ph.D. student, lifted the veil of secrecy by showing some of our exciting results, which we will soon release as a preprint.
Our article has just been published in the prestigious EMBO Journal. We are thrilled, as it will be featured on the cover of its August issue!
We focused on the CHIP ubiquitin ligase enzyme – a quality control factor responsible for the regulation and degradation of multiple protein targets, including those implicated in the pathogenesis of neurodegenerative diseases or cancer. We described a potential regulatory process enabling switching on/off activity of CHN-1, a worm analog of human CHIP, to maintain cellular homeostasis. We also identified a set of its new potential substrates, including AHCY‐1, a key enzyme involved in methylation - a process responsible e.g., for determining if particular DNA instructions would be processed or regulating proteins and lipids.
We are delighted that our recently released web server degronopedia.com has just passed 1000 queries!
Moreover, our PhD student Natalia gave two successful talks about it - at the EMBO Workshop Protein Termini in Bergen, Norway and virtually at the Dana-Farber Seminar Series. We are looking forward to introduce some new features soon, so stay tuned!
We published a preprint where we introduce DEGRONOPEDIA - a web server allowing for degron screening.
Degrons are short linear motifs critical for selective protein degradation. Our tool provides complex degron information (i.a. nearby residues that may be ubiquitinated, post-translational modifications, occurrence within a disorder region) and allows for Machine Learning predictions of protein termini stability.
DEGRONOPEDIA can be freely accessed at degronopedia.com
Our study on CHIP/UFD-2 molecular cooperation has been presented at the Ubiquitin & Friends Symposium in Vienna and GRK2243 Symposium in Würzburg by our talented Ph.D. students - Aniruddha Das and Pankaj Thapa.
We are very pleased how warmly it was received by the scientific community as expressed by the Travel Grant awarded to Aniruddha for one of the best presented posters.
Photo: @SFB_TPDvienna, Twitter
We released a preprint where we describe the engagement of the ubiquitin ligase CHIP by the nucleolus in response to proteotoxic stress.
These observations may be relevant in elucidating the mechanisms of nucleolar proteostasis and in the biology of cancer, whose development is influenced by nucleolar stress response pathways. Our study provides a solid basis for further exploring CHIP function in the nucleolus.
We released a preprint describing the first case of neurodevelopmental disorder in a patient with a de novo missense variant in a degron-binding pocket of ubiquitin ligase FEM1C. We used Caenorhabditis elegans as a model of the disease; mutant worms, similarly to the patient, also developed locomotion impairments.
This study was carried out in collaboration with the group of Prof. Rafał Płoski from the Medical University of Warsaw. We are looking forward to further fruitful collaborative research on possible mechanisms of pathogenicity underlying this mutation.
We are very pleased to inform that PI of our group - Wojciech Pokrzywa has obtained the five-year SONATA-BIS grant from the National Science Centre.
In the next years we will focus on mechanisms of protein adaptation to escape premature degradation by the ubiquitin-proteasome system. We are very excited for this new avenue of research!
In our recent preprint, we show that defects in red pulp macrophages - cells responsible for maintaining blood homeostasis - occur early in aging and disrupt iron turnover, contributing to elderly anemia.
We are delighted to announce that two of our Ph.D. students received their own PRELUDIUM grants from the National Science Centre (NCN).
Natalia Szulc will study how the cullin-RING ubiquitin ligase complexes avoid premature degradation, and Pankaj Thapa will investigate the molecular mechanism of the activity switch of the ubiquitin ligase CHIP.
We were honored to participate in the 25th Science Festival in Warsaw, one of the most significant popular science events in Poland. High school students warmly received our presentation on the secrets of Caenorhabditis elegans and its important role in aging research.
We hope that this tiny creature intrigued our listeners, and our lecture provided an overview of the current state of knowledge on mechanisms of aging.
Our research on muscular exopheresis in Caenorhabditis elegans is featured as a cover of the August issue of EMBO Reports!
Here we show that exophers are not only a storage compartment for cellular waste, but that muscular exopheresis represents a previously uncharacterized nutrient management program associated with nourishing the next generation of progeny.
What drives the prominent quality control ubiquitin ligase CHIP? Our new preprint on bioRxiv describes the mechanism by which CHIP is activated by another ubiquitin ligase, UFD-2, which enables the regulation of proteostasis and lipid metabolism.
Our results define the mechanism of synergistic cooperation of CHIP and UFD-2, which promotes structural gain of function in CHIP and regulates S-adenosylhomocysteinase, an enzyme crucial for cellular methylation and phosphatidylcholine synthesis.
During critical moments like differentiation, adhesion, and migration cells use sophisticated mechanisms that protect them from mechanical stress. Moreover, these mechanisms are also essential for maintaining tissues such as skeletal muscle, heart, and kidney as well as the immune system.
Here you can find our article, where we discuss recent advances in our understanding of mechanical stress protection.
The research unit FOR 2743 integrates mechanobiology and proteostasis research to elucidate how cells and tissues cope with force-induced protein unfolding. We identified mechano-protective proteostasis factors and signalling networks that regulate responses to mechanical stress.
Thanks to the extended funding we will further decipher principles of mechanical stress protection under physiological and pathophysiological conditions.
You can find more information here and here.
Our article on the different cellular effects of the intriguing mutant ubiquitin protein UBB+1 was published in Frontiers in Molecular Biosciences.
You can read here about how UBB+1 may extend lifespan, while on the other hand also leads to aggregation of toxic proteins.
Project Cellular adaptation to cold, funded by the NCN GRIEG grant & the Norwegian Financial Mechanism 2014 – 2021 for 1.499.998 EUR was opened.
We cannot wait to start the studies, together with our partner from the University of Oslo Prof. Rafał Ciosk, on how Caenorhabditis elegans can resist low temperature.
We received extension of the EMBO Installation Grant for the next 2 years!
Address
Laboratory of Protein Metabolism
International Institute of Molecular and Cell Biology in Warsaw
4 Ks. Trojdena Street
02-109 Warsaw, Poland
