Prof. Agnieszka Chacinska is a director of the International Institute of Molecular Mechanisms and Machines PAS (from 2020) and head of ReMedy, the International Research Agenda Program (from 2017). She received a PhD from the Institute of Biochemistry and Biophysics, PAS with Prof. Magdalena Boguta and post-doctoral training with Prof. Nikolaus Pfanner, followed by a junior group leader position at the University of Freiburg, Germany. Subsequently, she was a Head of the Laboratory of Mitochondrial Biogenesis at the International Institute of Molecular and Cell Biology in Warsaw (2009-2017), where she obtained a full professorship. In 2017, she undertook a position at the University of Warsaw, Centre of New Technologies. The Chacinska laboratory of Mitochondrial Biogenesis is currently moving to IMol PAS.
Prof. Agnieszka Chacińska is corresponding member of PAS, member of EMBO and Academia Europea.
Molecular and cell biology, biogenesis, mitochondria, transport and degradation of proteins, cellular protein homeostasis,
Mohanraj, K., Wasilewski, M., Benincá, C., Cysewski, D., Poznanski, J., Sakowska, P., Bugajska Z., Deckers M., Dennerlein S., Fernandez-Vizarra E., Rehling P., Dadlez M., Zeviani M., Chacinska A. (2019). Inhibition of proteasome rescues a pathogenic variant of respiratory chain assembly factor COA7. EMBO Molecular Medicine, 11(5). DOI: 10.15252/emmm.201809561
Topf, U., Suppanz, I., Samluk, L., Wrobel, L., Böser, A., Sakowska, P., Knapp, B., Pietrzyk, M. K., Chacinska*, A., & Warscheid*, B. (2018). Quantitative proteomics identifies redox switches for global translation modulation by mitochondrially produced reactive oxygen species. Nature Communications, 9(1), 324, DOI:10.1038/s41467-017-02694-8. (*co-corresponding authors)
Gold, V.A.M., Chroscicki, P., Bragoszewski, P., Chacinska, A. (2017). Visualization of cytosolic ribosomes on the surface of mitochondria by electron cryo-tomography. EMBO Reports, DOI 10.15252/embr.201744261.
Wrobel, L., Topf, U., Bragoszewski, P., Wiese, S., Sztolsztener, M.E., Oeljeklaus, S., Varabyova, A., Lirski, M., Chroscicki, P., Mroczek, S., Januszewicz, E., Dziembowski, A., Koblowska, M., Warscheid*, B., Chacinska*, A. (2015). Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. Nature, 524, 485-488. (*co-corresponding authors)
Bragoszewski, P., Wasilewski, M., Sakowska, P., Gornicka, A., Böttinger, L., Qiu, J., Wiedemann, N., Chacinska, A. (2015). Retro-translocation of mitochondrial intermembrane space proteins. Proc Natl Acad Sci U S A. 112, 7713-7718.
I graduated from the University of Wrocław in the field of medical biotechnology. During my studies, I participated in Socrates/Erasmus program at the University of Reims, France. Afterward, I completed the PhD course at the University of Birmingham in Prof. John Heath’s group. During 2011-2015 I was a postdoctoral fellow at the Cancer Research UK Manchester Institute in Signalling Networks in Cancer group led by Dr John Brognard. In 2015 I received Fuga grant by National Science Centre in Poland that allowed me to continue my research in the Laboratory of Experimental Medicine at the Centre of New Technologies, University of Warsaw. I was also awarded Homing grant by FNP (2017-2019), Sonata grant by NCN (2019-2021) and 3-year fellowship for Outstanding Young Researchers from the Ministry of Science and Higher Education (2016-2019). Currently, I supervise one PhD student and three undergraduate students. I will be taking the position of Group Leader at IMol in 2021.
Cancer, signaling, oncogenesis, kinases, targeted therapies
Upregulation of MLK4 promotes migratory and invasive potential of breast cancer cells.
Anna A. Marusiak*, Monika K. Prelowska, Dawid Mehlich, Michal Lazniewski, Klaudia Kaminska, Adam Gorczynski, Aleksandra Korwat, Olga Sokolowska, Hanna Kedzierska, Jakub Golab, Wojciech Biernat, Dariusz Plewczynski, John Brognard, Dominika Nowis. Oncogene, 2019
Somatically mutated ABL1 is an actionable and essential NSCLC survival gene.
Ewelina Testoni, Natalie L. Stephenson, Pedro Torres-Ayuso, Anna A. Marusiak, Eleanor W. Trotter, Andrew Hudson, Cassandra L. Hodgkinson, Christopher J. Morrow, Caroline Dive, John Brognard. EMBO Molecular Medicine, 2016
Recurrent MLK4 loss-of-function mutations suppress JNK signalling to promote colon tumorigenesis.
Anna A. Marusiak, Natalie L. Stephenson, Hayeon Baik, Eleanor W. Trotter, Yayong Li, Karen Blyth, Susan Mason, Phil Chapman, Lorena A. Puto, Jon A. Read, Claire Brassington, Helen K. Pollard, Chris Phillips, Isabelle Green, Ross Overman, Matthew Collier, Ewelina Testoni, Crispin J. Miller, Tony Hunter, Owen J. Sansom, John Brognard. Cancer Research, 2016
Paradox-breaking BRAF inhibitors are effective in melanomas that are resistant to BRAF-selective or BRAF plus MEK inhibitor combinations.
Maria R. Girotti, Filipa Lopes, Natasha Preece, Dan Niculescu-Duvaz, Alsonso Zambon, Lawrence Davies, Steven Whittaker, Grazia Saturno, Amaya Viros, Malin Pedersen, Bart M.J.M. Suijkerbuijk, Delphine Menard, Robert McLeary, Louise Johnson, Laura Fish, Sarah Ejiama, Berta Sanchez-Laorden, Neil Oliver Carragher, Kenneth MacLeod, Garry Ashton, Anna A. Marusiak, Alberto Fusi, John Brognard, Margaret Frame, Paul Lorigan, Caroline Springer, Richard Marais. Cancer Cell, 2015
Mixed lineage kinases activate MEK independently of RAF to mediate resistance to RAF inhibitors.
Anna A. Marusiak, Zoe C. Edwards, Willy Hugo, Eleanor W. Trotter, Maria R. Girotti, Natalie L. Stephenson, Xiangju Kong, Michael G. Gartside, Shameem Fawdar, Andrew Hudson, Wolfgang Breitwieser, Nicholas K. Hayward, Richard Marais, Roger S. Lo, John Brognard. Nature Communications, 2014
Prof. Magda Konarska is a deputy director for science at the International Institute of Molecular Mechanisms and Machines PAS (from 2021) and a deputy director of the International Research Agenda Program – ReMedy (from 2017). She received a PhD from the Institute of Biochemistry and Biophysics, PAS (with prof. Witold Filipowicz) and post-doctoral training with prof. Phillip A. Sharp, Cancer Research Center, MIT, Cambridge, MA, USA. Subsequently, for over 25 years, she was a Head of the Molecular Biology and Biochemistry Laboratory at the Rockefeller University, New York, NY, USA. In 2015, she resigned from the Evelyn Gruss Lipper Full Professor position at the Rockefeller University and moved to Center for New Technologies, University of Warsaw, where she established a Laboratory of RNA Biology. From 2021, she will continue to head the Laboratory of RNA Biology at IMol, PAS. Prof. Konarska is a corresponding member of PAS, a member of EMBO and Academia Europea.
RNA Biology, pre-mRNA splicing, spliceosome, snRNA core of the catalytic center
Konarska, M.M., Vilardell, J. and Query C.C. Repositioning of the reaction intermediate within the catalytic center of the spliceosome. Molecular Cell 21, 543-553 (2006).
Liu, L., Query, C.C. and Konarska, M.M. Opposing classes of prp8 alleles modulate the transition between the catalytic steps of pre-mRNA splicing. Nature Struct. Mol. Biol. 14, 519-526 (2007).
Smith, D.J., Query, C.C. and Konarska, M.M. Trans-Splicing to Spliceosomal U2 snRNA Suggests Disruption of Branch Site-U2 Pairing during Pre-mRNA Splicing. Molecular Cell 26, 883-890 (2007).
Smith, D.J., Konarska, M.M. and Query, C.C. Insights into branch nucleophile positioning and activation from an orthogonal pre-mRNA splicing system in yeast. Molecular Cell 34, 333-343 (2009).
Eysmont K, Matylla-Kulińska K, Jaskulska A, Magnus M, and Konarska MM. Rearrangements within the U6 snRNA core during the transition between the two catalytic steps of splicing. Molecular Cell 75(3):538-548 (2019).
Piotr received his PhD in 2012 from the University of Cambridge. He pursued his research at the MRC Laboratory of Molecular Biology under the supervision of Jan Löwe. In 2015 he moved for a postdoc in Martin Pilhofer’s group at ETH Zürich. Since May 2019, Piotr has been a junior group leader within the ReMedy International Research Agenda. Throughout his career, Piotr has been interested in investigating membrane-associated molecular machines that are essential in maintaining cellular architecture in health and disease.
Structural cell biology, electron cryotomography, membrane remodeling
Szwedziak P and Pilhofer M (2018) Bidirectional contraction of a type six secretion system. Nature Communications doi.org/10.1038/s41467-019-09603-1
Hussain S*, Wivagg CN*, Szwedziak P, Wong F, Schaefer K, Izore T, Renner LD, Holmes MJ, Sun Y, Bisson-Filho AW, Walker S, Amir A, Löwe J, Garner EC (2018) MreB filaments align along greatest principle membrane curvature to orient cell wall synthesis. eLife 10.7554/eLife.32471
Szwedziak P*, Wang Q*, Bharat TAM, Tsim M, Löwe J (2014) Architecture of the ring formed by the tubulin homologue FtsZ in bacterial cell division. eLife 10.7554/eLife.04601
Szwedziak P, Löwe J (2013) Do the divisome and elongasome share a common evolutionary past? Curr Opin Microbiol 16:745-751
Szwedziak P, Wang Q, Freund SM, Löwe J (2012) FtsA forms actin-like filaments. EMBO J 31:2249-2260
Directors of ReMedy International Research Agenda Programme
firstname.lastname@example.org (ReMedy coordinator)
Prof. Agnieszka Chacińska and Prof. Magda Konarska are directors of the programme Regenerative Mechanisms for Health (ReMedy) funded by the Foundation for Polish Science, transferred from the University of Warsaw to the International Institute of Molecular Mechanisms and Machines PAS (February 2021). Profs. Agnieszka Chacińska and Magda Konarska are corresponding members of PAS, members of EMBO and Academia Europea.
ReMedy's activities are focused on research on regenerative mechanisms at the molecular level, including the understanding of the mechanisms of cells' response to disorders caused by environmental, disease or aging factors. This knowledge is expected to help in the development of new therapies and drugs to maintain health and heal, among others, age-related neurodegenerative diseases as well as cancer. Within the ReMedy programme, new group leaders are recruited to form their groups and run independent research enriching the goals of ReMedy. Profs. Chacinska and Konarska serve as mentors to newly recruited group leaders.
molecular and cell biology, biomedical and biological chemistry, stress responses and mechanisms, molecular machines
Eysmont K, Matylla-Kulińska K, Jaskulska A, Magnus M, Konarska MM. (2019) Rearrangements within the U6 snRNA core during the transition between the two catalytic steps of splicing. Mol. Cell 75 (3), 538-548.e3, doi: 10.1016/j.molcel.2019.05.018
Mohanraj K, Wasilewski M, Benincá C, Cysewski D, Poznanski J, Sakowska P, Bugajska Z, Deckers M, Dennerlein S., Fernandez-Vizarra E, Rehling P, Dadlez M, Zeviani M, Chacinska A. (2019). Inhibition of proteasome rescues a pathogenic variant of respiratory chain assembly factor COA7. EMBO Molecular Medicine, 11(5). doi: 10.15252/emmm.201809561
Kuzniewska B, Cysewski D, Wasilewski M, Sakowska P, Milek J, Kulinski TM, Winiarski M, Kozielewicz P, Knapska E, Dadlez M, Chacinska A, Dziembowski A, Dziembowska M. (2020). Mitochondrial protein biogenesis in the synapse is supported by local translation. EMBO Rep. 18;21(8):e48882. doi: 10.15252/embr.201948882.
Samluk L, Urbanska M, Kisielewska K, Mohanraj K, Kim MJ, Machnicka K, Liszewska E, Jaworski J, Chacinska A. (2019). Cytosolic translational responses differ under conditions of severe short-term and long-term mitochondrial stress. Molecular Biology of the Cell, 30(15):1864-1877. doi: 10.1091/mbc.E18-10-0628.
Topf U, Uszczynska-Ratajczak B, & Chacinska A. (2019). Mitochondrial stress-dependent regulation of cellular protein synthesis. J Cell Sci, 132(8), doi: 10.1242/jcs226258.