Project Number: 2012/04/S/NZ1/00729
Funds: 612.000 PLN
Duration of the project: October 2012-September 2016
Title of the project: A code for RNA recognition in RNA–RRM interactions
Project leader: Martyna Nowacka, PhD
Summary of the project:
RNA-recognition motif (RRM) is a small RNA-interacting protein domain that plays a role at every stage of RNA life cycle: splicing, editing, export, degradation and regulation of translation. RRMs are very common in all kingdoms of life, but particularly abundant in eukaryotes. Many well-characterized proteins that contain RRMs are involved in developmental processes, cellular response and control of gene expression. The RRM interacts with RNA molecules in a sequence- and sometimes also RNA secondary structure-dependent manner. Despite the large body of data available on sequence-specific RRM-RNA interactions, including numerous structures of RRM-RNA complexes, the “recognition code” is still not fully understood, and we cannot predict the RRM ligands from its protein sequence alone. In this project we were using a multidisciplinary approach towards better understanding of RRM-RNA recognition and thus towards a more complete bigger picture of the whole RRM superfamily.
The results of the RRM domains classification according to their sequence similarity were gathered in the new database: the RRM DB (the RNA Recognition Motif Database) available at http://genesilico.pl/rrm/. The RRM DB is a valuable tool providing the users with general knowledge about RRMs and proteins containing these domains (literature, structures, and other useful links). It can be particularly useful for those who are interested in RRM phylogenetic studies. In this project the RRM DB was used as a starting point for further theoretical and experimental studies of so far unexplored RRM domains.
The results obtained in the project may help to better understand the basics of important cellular processes, taking place with the participation of protein-RNA complexes, and in a long term, serve as a source of information for designing new and specific RNA-binding domains.
Project supported by National Science Center Poland in frame of FUGA: post-doctoral internships programme
International Institute of Molecular and Cell Biology received grants to support technology transfer in BioCentrum Ochota consortium. The grants are sponsored by Operational Program – Human Capital and the programme of the Minister of Science and Higher Education – Kreator Innowacyjności.
European Social Fund, Operational Program – Human Capital
“Support for bio tech med scientists in technology transfer”;
(UDA-POKL.08.02.01-14-041/09-00)
Budget: 2 586 000 PLN
Duration of the project: April 2010 – October 2014
Activities within the project for BioCentrum Ochota consortium:
- 12 research stipends for innovative projects for PhD students working in BioCentrum Ochota institutes
- 12 two-month placements for BioCentrum Ochota scientists
- 150 of training courses on issues such as: R&D project management, raising a company, commercialization of R&D results, IPR, negotiations in business
- Meetings and a conference promoting tech transfer and giving an opportunity to launch science-industry cooperation.
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Ministry of Science and Higher Education, Kreator Innowacyjności , creation of Technology Transfer Office for BioCentrum Ochota, (PMKI/W/30-06.09)
Budget: 422 990 PLN
Duration of the project: September 2010 – March 2013
Partner – Nencki Institute of Experimental Biology
Activities within the project for BioCentrum Ochota consortium:
- Increasing the number of patentable inventions (identifying applicable projects and assisting in their commercialization),
- Awareness raising in BioCentrum Ochota scientists of IPR and R&D commercialization (12 training courses on IPR and commercialization),
- Promoting intellectual and infrastructural potential of BioCentrum Ochota institutes,
- Enhancing science – industry cooperation in bio-tech –med fields.
Current news: www.biotechip.pl
Contact: Magdalena Powierża
This email address is being protected from spambots. You need JavaScript enabled to view it. , tel. 22 597-07-16
Project Number: Pomost/2010-1/1
Funds: 420.000 PLN
Duration: 2010-2013
Title of the project: Functional characterization of the interactions between endosomal adaptor proteins APPL and Dvl proteins in the Wnt signaling pathway
Project leader: Magdalena Banach-Orłowska, PhD
There is a growing body of evidence highlighting the impact of endocytosis on cell signaling. It is commonly accepted that endocytosis is not only responsible for signal attenuation but it can also positively contribute to signal propagation. Many endocytic proteins actively participate in signal transduction, and these processes are currently intensively investigated.
Multifunctional adaptor proteins APPL1 and APPL2 represent interesting examples of endocytic proteins involved in signaling. They have been shown to interact with many partners involved in various signaling pathways mediating apoptosis, cell survival, cell proliferation and chromatin remodeling. The data obtained in our laboratory indicate that APPL1 and APPL2 proteins function as positive regulators of the Wnt pathway.
Wnt signaling governs crucial biological processes such as cell proliferation, adhesion or migration. Understanding the exact mechanisms by which Wnt signaling operates, including the role of APPL proteins in this process, is essential to fight diseases caused by abnormalities in this pathway.
In this project we investigate the role of multifunctional endocytic proteins APPL1 and APPL2 in the regulation of the canonical (b-catenin dependent) and non-canonical (planar cell polarity; PCP) Wnt signaling pathways. We test the impact of APPL proteins on the initial stages of the canonical Wnt signaling route by studying their newly identified interaction with Dishevelled (Dvl) proteins, the known positive regulators of the Wnt pathway. Moreover, we are interested in studying the influence of APPL on the non-canonical pathway in the context of APPL-Dvl interactions, since Dvl proteins play a crucial role in the PCP pathway.
In a broader sense, the proposed project should contribute to better understanding of mechanisms coordinating the endocytic and signaling machineries.
With respect to the methodology used in our laboratory within this project, our main experimental system are cultured mammalian cells. We use a variety of methods, including cell fractionation, confocal microscopy, biochemical characterization of proteins and their post-translational modifications, identification of protein interacting partners, quantitative RT-PCR to investigate expression of Wnt target genes, and transcriptional reporters to measure the activity of the Wnt signaling pathway.
Project supported by Foundation for Polish Science in frame of the Parent-Bridge programme financed by the European Union via the European Regional Development Fund.
It was the commissioned project of the Ministry of Science and Higher Education entitled: "Advanced molecular methods in haematology. Work out and implementation of standards of minimal residual disease, posttransplant chimerism and marker translocations analysis." The project with the overall budget of about 3 mln PLN linked elements of pediatric and adult molecular haematology related to basic research and practical applications. The consortium was composed of the major Polish centers of molecular haematology in Poznan, Warsaw, Cracow, Lublin and Zabrze what constituted the core of reference laboratories network active in this area in Poland. Haematological disorders selected for the study by the consortium were: pediatric acute lymphoblastic leukemia (ALL), pediatric and adult acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and non-Hodgkin lymphomas (NHL); they were chosen as model disorders being already analysed on a molecular level in some of the Polish centers. A posttransplant chimerism and a minimal residual disease (MRD) were being analysed in connection to the disorders listed above. The project also aimed at constructing the database linking available clinical and molecular data of patients recruited to the program and also on establishing the multicenter collection of relevant biological material. The program was initiated at IIMCB and was being conducted by Prof. Michal Witt and coordinated by Dr. Malgorzata Mossakowska. The project resulted in two monographs:
Hematologia molekularna. Patogeneza, patomechanizmy i metody badawcze. Witt M, Szczepanski T, Dawidowska M (red.), OWN Poznan , 2009 (in Polish)
Molecular aspects of hematological malignancies. Laboratory problems from a clinical perspective. Eds. M Witt, M Dawidowska, T Szczepanski, Springer Verlag (in preparation)
"Genetic and environmental factors of longevity"
supported by:
Ministry of Science and Information Society Technologies
(State Committee for Scientific Research )
(KBN) grant PBZ-KBN-022/PO5/1999
coordinated by:
International Institute of Molecular and Cell Biology in Warsaw
Centenarians in Poland
NATIONAL CENSUS OF POPULATION AND HOUSING 2002
POPULATION PROJECTION OF POLAND 2003-2030
Central Statistical Office of Poland (GUS)
Number of centenarians:
| Year | Total | men | woman | city | village |
| 2002 | 1541 | 326 | 1215 | 998 | 543 |
| 2030 | 9218 | 904 | 8314 | 6350 | 2868 |
Study group:
Total/ F/ M
• Patients visited 400/319/81
confirmed age 344/295/49
• Age range: 100-108
• Median age: 100.8 years
• Patients were visited at home
•Timeframe of the project: May 2002- December 2004
Title of project: Screening for novel functions of endocytic and autophagic proteins in the regulation of gene expression, cell growth and carcinogenesis.
Person responsible for project (IIMCB): Iwona Pilecka, PhD
Norwegian partner: Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo (IBMS)
Person responsible for project (IBMS): Anne Simonsen, PhD, Associate professor
Summary of the project:
The Project, proposed by two research groups of the International Institute of Molecular and Cell Biology (IIMCB) in Warsaw and of the Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, belongs to the field of pathogenesis and genetics of cancerous diseases. It aims to identify candidate genes potentially involved in tumorigenesis, using state-of-the-art molecular screening approaches.
The Project is based on novel data indicating that hyperproliferative conditions underlying cancer can result from the perturbation of endocytosis and autophagy, two cellular processes involving lysosomal organelles. Endocytosis is a process of vesicular transport in cells which ensures uptake of extracellular molecules (e.g. nutrients or growth factors) and their subsequent degradation in lysosomes or recycling back to the plasma membrane. Autophagy is a lysosomal pathway for bulk degradation of cytoplasmic contents and whole organelles which complements apoptosis. In recent years, several endocytic and autophagic proteins, initially characterized in the context of vesicular transport, were reported to act as tumor suppressors or function directly as regulators of transcription in the cell nucleus. However, no systematic studies were undertaken to search for such alternative functions of endocytic/autophagic proteins or to elucidate the underlying molecular mechanisms, and our Project aims to fill this gap by an innovative and comprehensive approach.
We thus propose to establish a screening platform for cell-based assays and perform a screen for an initial set of endocytic and autophagic proteins for their potential roles in carcinogenesis by measuring their involvement in signal transduction, transcription and cell proliferation, by RNA interference-mediated knockdown. The Project activities are divided into three main tasks within a total timeframe of 24 months. We will generate libraries of siRNA reagents for the selected endocytic/autophagic genes (Task I). These reagents will be used in four primary screens, using automated microscopy-, fluorescence- and luminescence-based readouts in a middle-throughput scale format (Task II), followed by validation of positives in two secondary assays (Task III). Upon Project completion, we expect to have identified candidate genes potentially involved in tumorigenesis, for future testing in clinical samples.
Thus the Project should contribute to conceptual advance of knowledge on molecular mechanisms of cancer but equally important will be an establishment of a largely automated screening platform at IIMCB as a basis for further high-throughput, eventually genome-wide, screening projects. In a long term this will contribute to introducing novel technologies and systems biology approaches into the field of cancer research in Poland.
IIMCB was one of the major initiators of multidisciplinary projects on ageing and currently is a coordinator of the ministerial commissioned project Medical, psychological and economical aspects of aging in Poland. The largest country’s project in this area of research with its budget over 12 mln PLN aims at conducting an interdisciplinary study of various aging-related problems. About 6000 patients will participate in a survey and over 1500 patients in 8 regions will be examined by geriatricians within the framework of this project. Biological material (DNA bank) will be deposited at IIMCB, also our Institute will provide the whole consortium with an database gathering all tests results. Four subprojects focus on a large-scale epidemiological studies, two on physical and architectural barriers for the old population. Specialists involved range from sociologists, psychologists, economists and demographers to geriatrists, cardiologists, nephrologists, neurologists, epidemiologists and molecular biologists. Final target is an ultimate definition of needs of aging population in terms usable in social policy, administrative care etc. that can shape future decision-making in this area.
The project is conducted at the International Institute of Molecular and Cell Biology in Warsaw with Prof. Piotr Bledowski (President of Polish Gerontological Society) as a head of the project and Dr. Malgorzata Mossakowska as coordinator.
More information (in Polish): http://polsenior.iimcb.gov.pl/
Role of ciliary proteins in pathogenesis of cilia-related disorders
The involvement of mutations of ciliary proteins, their dysfunction, erratic cytoplasmic assembly, defective flagellar transport, etc. on pathomechanism of primary ciliary dyskinesia and retinitis pigmentosa will be studied. Both autosomal recessive and X-linked forms of disorders will be investigated. The research methods applied will include in vitro analysis of ciliary proteins in newly developing respiratory cilia (in vitro ciliogenesis), immunofluorescence staining of ciliary proteins and sequencing of genes coding for proteins involved or potentially involved in cilia function/assembly. Involvement of these proteins in a pathomechanism of human retinal dysfunction will be deduced. Also, proteins involved in human visual processes will be analyzed. Particular effort will be placed on introducing for the first time in the country a high speed video analysis of cilia motility; correlations between the type of dismotility with genetic/structural factors will be performed. Analysis of in vitro ciliogenesis will be offered to clinical partners as a modern tool of functional diagnosis in primary PCD suspects.
The program is being conducted by Prof. Michal Witt in collaboration with Prof. Heimut Omran from Department of Pediatrics and Adolescent Medicine, University of Freiburg, Germany.
Project's Number: PSPB-094/2010
Title of project: The role of tumor susceptibility gene 101 (Tsg101) in transcriptional regulation in health and disease.
Person responsible for project (IIMCB): Professor Marta Miaczynska
Swiss partner: Department of Biochemistry Sciences II, University of Geneva (UNIGE)
Persons responsible for project (UNIGE): Professor Jean Gruenberg and Professor Marcos Gonzalez-Gaitan
Summary of the project:
Tsg101 protein has two-fold significance for human health: it represents an important anti-viral drug target and its deregulated expression is a hallmark of various cancer types. In fact, both pro- and anti-oncogenic activities of Tsg101 have been reported. At a cellular level, Tsg101 directs cargo sorting during endocytosis, is involved in cytokinesis and budding of HIV and other viruses. Novel data of the IIMCB applicant indicate that Tsg101 has an alternative function as a regulator of transcription in different cell signaling pathways. These data are the basis for the current proposal.
Due to the opposing roles of Tsg101 in specific transcriptional responses, we hypothesize that Tsg101 could act either as a tumor suppressor or a cancer-promoting protein depending on the tumor-specific aberration in signaling pathways. This would explain the controversy in the literature. Moreover, the role of Tsg101 in transcription has not been systematically investigated. Our project aims to fill this gap by a comprehensive combination of innovative experimental approaches.
We propose to study the novel transcriptional roles of Tsg101 in cultured cells, in model organisms as well as in normal and diseased human tissues, complemented by in silico analyses. To achieve its goals, the project involves a wide spectrum of complementary and innovative methodologies, ranging from molecular and cellular assays, global transcriptome analyses, functional studies in model organisms, to human cancer arrays. Complementing the Affymetrix microarrays, a key innovative technology to obtain unbiased and precise transcriptomic results will be the NanoString mRNA profiling.
The results of the project are expected to have three-fold significance. First, they should identify the molecular mechanisms and targets of Tsg101 action in transcription. This is expected to provide conceptual advances of fundamental knowledge about the relationship between endocytosis, transcription and cancer. Second, the project should identify any potential adverse effects of an available Tsg101 inhibitor on cellular transcription. This will be of applicable value for further development of anti-viral drugs with minimal side effects targeting Tsg101. Third, the knowledge of the detailed expression profile of Tsg101 and its transcriptional targets in various clinically characterized tumors could help to resolve controversy over the pro- or anti-oncogenic properties of Tsg101. This may contribute to diagnostic or prognostic applications in the clinical practice.
www.programszwajcarski.gov.pl
www.swiss-contribution.admin.ch/poland
Project supported by a grant from Switzerland through the Swiss Contribution to the enlarged European Union
EU FP7 Marie-Curie Initial Training Network
Title of the project: Transport and signalling mechanism in polarized cells
Acronym: TRANSPOL
Number of the project: 264399
Project Coordinator: Prof. Rolf Heumann, Department of Biochemistry II, Ruhr-University Bochum, Germany
IIMCB Partner: Prof. Marta Miaczynska, Laboratory of Cell Biology
TRANSPOL website: http://www.ruhr-uni-bochum.de/mol-neurobio/TRANSPOL
