Projects solved in year 2011
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Research Task - Ministry of Health
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Reg. number Research Task MZ0UHKT2005 Title The Role of Molecular Biology in Clarifying Pathogenesis and in Diagnosis of Haematopoeitic Disorders. The Application of Stem Cells in the Treatment of Haematopoeitic and other Tissue Disease. Duration 2005 - 2011 Main researcher MUDr. Jaroslav Čermák, CSc. Annotation Application of molecular biology investigations in the elucidation of pathogenesis and in the diagnosis and treatment of haematopocitic disorders. Monitoring the importance of changes in the structure and function of the genome for the diagnosis, prognosis and treatment of congenital and acquired heamatopoietic diseases. Monitoring the importance of the activation of individual coagulation systém components in malignant haematopoetic diseases. Clarifying the molecular basis of rare erythrocyte phenotypes and certain congenital disorders of erythropoeisis. The haematopoeitic stem cell and its application in the treatment of haematopoeitic and other tissue diseases. Manipulation of haematopoietic stem cell transplantation in the treatment of malignant annd non-malignant haematopoietic diseases. Monitoring the safety of mobilisation and apheresis of peripheral haematopoietic stem cells. Monitoring genetic factors that affect the success of haematopoeitic stem cell transplantation.
Czech Science Foundation (GA CR)
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Reg. number GA CR GA ČR P304/10/1511 Title Duration 2010 - 2012 Main researcher Doc. RNDr. Jitka Forstová, CSc., Přírodovědecká fakulta UK Co-researcher Mgr. Vojtěch Šroller, Ph.D. Annotation -
Reg. number GA CR GA301/09/1026 Title Proteomic analysis of suberoylanilide hydroxamic acid (SAHA) effects on human leukemic cells Duration 2009 - 2011 Main researcher RNDr. Kateřina Kuželová, Ph.D. Annotation Suberoylanilid hydroxamic acid (SAHA) was recently approved for the treatment of cutaneous T-cell lymphoma and is evaluated in clinical trials for many other oncologic and hematologic applications. However, the mechanism of its action is complex and poorly understood. SAHA is known to induce apoptosis or other form of cell death in the majority of cancer cells while the normal cells appear to be relatively resistant to its effects. The raisons of this difference are at present unknown. The proteomicanalysis of changes occuring after SAHA treatment of both leukemic and normal cells will reveal the main signal transduction pathways regulating the cell response to the therapy. We will focuse to subtoxic concentrations of the drug as we have recently observed significant increase in the adhesivity of the transformed, but not normal hematopoietic cells under these conditions. Nevertheless, the analysis of SAHA effects on the protein level is also required for higher doses which have been until now studied on the gene transcription level only. -
Reg. number GA CR GA521/09/1525 Title Biosafe plant virus expression system for transient production of human papillomavirus oncoproteins and their use for therapeutic vaccine development Duration 2009 - 2011 Main researcher RNDr. Noemi Čeřovská, CSc., Ústav experimentální botaniky AV ČR, v. v. i. Co-researcher RNDr. Michal Šmahel, Ph.D. Annotation The aim of the proposed project is to prepare protein immunogens derived from human papillomavirus HPV16 and optimization of their expression in plants for developing experimental therapeutic anti-HPV16 vaccines. We propose the production of different proteins containing immunodominant HPV16 epitopes from the E7 or E6 oncoproteins. We would like to develop the conditions leading to the high transient expression levels of heterologous proteins. The novelty of our attitude will be the new systems reliedon a deconstructed TMV and PVX replicon strategy, which allows a stringent containtment of the recombinant viruses and provides us with biosafe transient expression units. The used host plants will be transgenic and non-transgenic N. benthamiana, a nonfood and nonfeed. We propose a strategy of economical expression of pharmaceutical proteins using viral vectors with high biosafety containment and without Agrobacterium contamination. Immunogenicity of the produced proteins will be examined in a mouse model by the detection of specific humoral, cell-mediated, and anti-tumor immunity. -
Reg. number GA CR GP301/09/P579 Title Importance of miRNA deregulation in myelodysplastic syndromes and in other hematological clonal diseases Duration 2009 - 2011 Main researcher Ing. Michaela Merkerová, Ph.D. Annotation Myelodysplasic syndrome (MDS) is a family of heterogeneous blood disorders that originate in a pluripotent stem cell. They are considered a preleukemic condition. An intensive research has been focused on MDS pathogenesis and cytogenetic aberrations associated with approx. 50% of MDS have been revealed; however, reasons for MDS progression remain unknown. To date, genes responsible for MDS has not been identified and it is uncertain whether chromosomal aberrations are the primary reason or a secondary event. microRNAs (miRNAs), components of the RNA interference mechanism, play key roles in many cell processes incl. hematopoiesis. miRNA deregulation is responsible for cell transformation in a variety of tumors and leukemia; however, miRNA importance in MDS has not been investigated yet. By expression analysis, we want to identify miRNAs deregulated in MDS and monitor changes in miRNA expression profile in different MDS stages. We want to correlate deregulated miRNA levels to amounts of their target gene expression products and reveal impacts of miRNA deregulation on MDS progression.
Internal Grant Agency of the Ministry of Health
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Reg. number IGA MH IGA MZd NT 11299 Title Duration 2010 - 2015 Main researcher Prof. MUDr. Marek Trněný, CSc., Všeobecná fakultní nemocnice Praha Co-researcher MUDr. Veronika Válková, CSc. Annotation -
Reg. number IGA MH IGA MZd NT 11227 Title Duration 2010 - 2014 Main researcher Prof. MUDr. Viklický Ondřej, CSc., Institut klinické a experimentální medicíny – Praha Co-researcher Prof. MUDr. Radim Brdička, DrSc. Annotation -
Reg. number IGA MH IGA MZd NT 11555 Title Duration 2010 - 2014 Main researcher Mgr. Kateřina Machová Poláková, PhD. Annotation -
Reg. number IGA MH IGA MZd NT 11541 Title Duration 2010 - 2013 Main researcher RNDr. Michal Šmahel, PhD Annotation -
Reg. number IGA MH NS10 634-3/2009 Title Immunological studies with mouse and human cells transformed by the bcr-abl fusion gene Duration 2009 - 2011 Main researcher Prof. MUDr Vladimír Vonka DrSc. Co-researcher RNDr. Šárka Němečková, DrSc., RNDr. Ruth Tachezy, Ph.D., MUDr. Hana Klamová, CSc., MUDr. Petr Kobylka, CSc., Doc. RNDr. Petr Stöckbauer, CSc., Mgr. Martina Petráčková, Mgr. Vincent Lučanský, Monika Kremeníčková, Mgr. Ing. Libor Staněk Annotation The proposed study aims at broadening the present knowledge of the immune reactivity against brc-abl-transformed cells in mice.. New vaccines based on gene-modified cells will be constructed and tested in animals which had been inoculated with the tumour cells . It is expected that stimuli for forming a new strategy for treatment of chronic myeloid leukemia (CML) will be the outcome of these experiments. As a preparatory step, attempts will be made to isolate bcr-abl-expressing cell lines from cultures of human umbilical stem cells, and, later on, from cultures of cells obtained from CML patients. These cell lines will serve for monitoring specific immune reactions of the patients and in the future may develop into candidates for autologous therapeutic vaccines. -
Reg. number IGA MH NS10/656-3/2009 Title HPV type-specific prevalence in the screening population of women Duration 2009 - 2011 Main researcher RNDr. Ruth Tachezy, PhD. Annotation The age-specific prevalence of HPV in the cervical smear of the population of women in the Czech Republic attending preventive gynecologic examinations (oportunistic screening) and the type-specific distribution in this group of women will be studied. The type-specific distribution in the group of subjects with normal cytological findings and women recruited from the screening population which will have suspicious and/or pathological findings will be compared. Furthermore, the comparison of the widely used method for HR HPV detection with the very specific and very sensitive method for HPV detection and typing will be done in regard to the capability of detection of HR HPV types present in the population of Czech women. these data are necessary for the surveillance of HPV type-specific prevalence in the onset of vaccination against several HPV types. -
Reg. number IGA MH NS10623-3/2009 Title New molecular markers for monitoring of residual disease in acute myeloid leukemia patients Duration 2009 - 2011 Main researcher RNDr. Cedrik Haškovec, CSc. Annotation The project aims to find new molecular markers for monitoring Minimal Residual Disease especially for those patients with acute myeloid leukemia (AML), who have no suitable specific marker. In samples from AML patients we will determine expression, mutation, and methylation of selected genes; and results will be compared with the course of patients’ treatment. Finding new molecular markers will contribute to the individualization of treatment and increase the survival of these patients. -
Reg. number IGA MH NS10660-3/2009 Title Experimental vaccines against WT1 for immunotherapy of tumors Duration 2009 - 2011 Main researcher RNDr. Šárka Němečková, DrSc. Co-researcher M. Indrová, ÚMG, AV ČR Annotation WT1 gene is highly expressed in myeloid leukemia and in some solid tumors. WT1 is an autologous protein, though it is immunogenic in humans, it was evaluated as a promising target antigen in immunotherapy of tumors. WT1 gene expression is controlled by epigenetic mechanisms. It was shown, that inhibitors of chromatin modification such as 5-azaC, 5-azadC and trichostatin A increase WT1 gene expression, which could increase sensitivity of tumor cells to effect of immunization. The aim of the project is construction of recombinant vaccines against WT1 antigen, based on efficient cleavage and presentation of optimized multiepitopes for immunotherapy of malignancies expressing WT1 gene on mouse model. The second goal is to find scheme of combined chemo-immunotherapy of tumors, based on epigenetic sensitization of tumor cells for the effect of WT1 specific adaptive cell mediated immunity elicited by recombinant vaccines. -
Reg. number IGA MH NS9637-4 Title Interactions between nuclear and nucleolar proteins controlling cell proliferation and apoptosis effectors during leukemogenesis and therapy of leukemias Duration 2009 - 2011 Main researcher Mgr. Barbora Brodská, PhD. Co-researcher Mgr. Petra Otevřelová, Ing. Michaela Pluskalová, PhD., Ing. Dana Grebeňová Annotation Study of interactions between nuclear and nucleolar factors controlling cell proliferation and effectors of programmed cell death. Modifications and translocations during leukemogenesis and drug induced apoptosis in normal leukocytes and leukemic cells. The study of interaction complexes in normal blood cells and leukemic cell lines using: qRT-PCR, immunoblotting, yeast two-hybrid system, affinity chromatography, mass spektrometry, flow cytometry, immunofluorescence microscopy. -
Reg. number IGA MH NS9907-4 Title Prevalence and biological consequencies of Human Herpesvirus 6 (HHV6) chromosomal integration in paediatric and adult patients treated with malignant disease Duration 2009 - 2011 Main researcher MUDr. Petr Hubáček, Klinika dětské hematologie a onkologie, 2. LF UK a FN Motol Co-researcher Doc. MUDr. Petr Cetkovský, Ph.D. Annotation Prevalence of HHV6 chromosomal integration in severely immunosupressed patients endangered by highest risk of misinterpretation of HHV6 PCR positive result and side effects of subsequent virostatic therapy. Clarify of so far unknown serological reaction in HHV6 chromosomal integration carriers against HHV6 by IgM and IgG detection in the samples drawn at diagnosis. Detection of the place and size of viral DNA integration into human genome by FISH method and PCR in cells of the carriers and subsequent mRNA analysis with estimation of influence of transribed proteins on inter- and intracellular signaling. Confirmation of same frequency of HHV6 chromosomal integration in adult and children treated with malignant disease. -
Reg. number IGA MH IGA MZd NS 9970 Title Duration 2008 - 2011 Main researcher Doc. MUDr. Marie Černá, CSc., 3. lékařská fakulta Univerzity Karlovy Praha Co-researcher MUDr. Markéta Marková, CSc. Annotation -
Reg. number IGA MH NS/9984-4 Title The role of chronic infection in etiopathogenesis of prostate Duration 2008 - 2011 Main researcher MUDr. Jiří Heráček, PhD, 3. LF UK, Urologická klinika Co-researcher MUDr. Jiří Heráček, PhD, FNKV, Urologická klinika, RNDr. Eva Hamšíková Annotation The population will consist of subjects with PC (histologically verified) from retropubic radical prostatectomy or benign prostatic hyperplasia from tissue from suprapubic transvesical prostatectomy. In serum positive patients will be performed examination of the tissue specimens and their collection for the purpose of molecular genetic testing. The project focuses on actual oncology issues. We expect the results to be used in applied research, long-time patient dispensarization, PC screening and improving diagnostic and therapeutic approaches -
Reg. number IGA MH NS9634-4/2008 Title Determination of SNP and DNA methylation profiles in patients with myelodysplatic syndrome by microarrays. Duration 2008 - 2011 Main researcher Mgr. Monika Beličková Co-researcher RNDr. Hana Bruchová, Ph.D., Prof. MUDr. Radim Brdička, DrSc., Doc.MUDr. Jaroslav Čermák, CSc. Annotation The aim of the project is determination of SNP and DNA methylation profiles in MDS patients. We will use Illumina microarrays, “Cancer SNP Panel” for detection of 1421 SNPs located in 408 genes and “Methylation Cancer Panel” for detection of 1505 CpG loci in 807 genes. We will determine patterns in patients and those will be compared to the patterns of healthy subjects to identify significant differences. These deviations may reveal genes involved in the pathogenesis of MDS. Moreover, the patterns will be compared between low and high risk patients and also transformed patients with acute myeloid leukemia (AML). The comparative analysis may determine genes associated with disease progress or transformation into AML.
Grant Agency of the Academy of Sciences CR
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Reg. number GA AS CR IAA500960903 Title Development of a Novel Recombinogenic Technique for Chloroplast Transformation and its Use for Production of human papillomavirus E7 Protein in Plants Duration 2009 - 2012 Main researcher Doc. RNDr. Josef Vlasák, CSc., Biologické centrum AV ČR, v.v.i. Co-researcher RNDr. Viera Ludvíková Annotation Our aim is to develop more efficient method for plant chloroplast transformation using biolistic bombardment with linear DNA vectors together with chloroplast cassettes expressing bacteriophage lambda Red proteins. The idea stems from experiments with targeted insertion mutagenesis in yeast, cyanobacteria, and E. coli, where DNA ends promote recombination, and lambda Red proteins Exo, Beta, and Gam are very efficient in short recombinogenic ends protection and processing. Linear vectors can be generated conveniently as PCR products with synthetic primer ends that are homologous to sequence targets in the chloroplast genome. Chloroplast vectors will carry marker genes and also human papillomavirus oncogene E7 in the form of highly immunogenic but nononcogenic fusion E7GGG/GUS. It is our goal to obtain transplastomic plants producing this antigen with potential use as therapeutic vaccine. Viral antigens produced in plants will be assayed with antibodies and tested in mice. -
Reg. number GA AS CR KAN200670701 Title Surface plasmon resonance biosensors and protein arrays for medical diagnostics Duration 2007 - 2011 Main researcher Ing. Jiří Homola, CSc., Ústav radiotechniky a elektroniky AV ČR, v.v.i. Co-researcher Prof. Ing. Jan Evangelista Dyr, DrSc. Annotation The goal of this project is to advance knowledge in the field of photonic nanostructures and biofunctionalizations to enable development of a new generation of surface plasmon resonance (SPR) biosensors for detection of molecular analytes. Research in photonic nanostructures will focus on metal-dielectric structures with localized or guided surface plasmons with potential for SPR sensing. In the area of biofunctionalizations, research effort will concentrate on assemblies of biological and synthetic macromolecules with controlled composition and architecture. The project also encompasses development of novel types of optical biosensors for medical diagnostics, specifically, multichannel biosensors and multifunctional protein chips for new methods of diagnostics of myelodysplastic syndrome, biosensors for diagnostics of herpetic infections, and biosensors for detection of biomarkers of health problems caused by polycyclic aromatic hydrocarbons and endocrine disruptors.
Ministry of Education, Youth and PT
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Reg. number MEYS MŠMT OC 10042 Title Duration 2010 - 2012 Main researcher RNDr. Cedrik Haškovec, CSc. Annotation -
Reg. number MEYS 2B06088 Title Application of toxicogenomics to study mechanisms of the action of environmental pollutants on human health. Duration 2006 - 2011 Main researcher MUDr. Radim Šrám, Dr.Sc., Ústav experimentální medicíny AV ČR, v.v.i. Co-researcher Prof. MUDr. Radim Brdička, Dr.Sc. Annotation In order to get more inside into the molecular mechanisms of various adverse effects of environmental pollutants on human health and their potential transfer from mothers to fetus, we will identify major changes in the gene expression in placenta and lymphocytes of mothers heavily exposed to tobacco smoke (Step 1) and other environmental pollutans (Step 2). The exposure of subjects to genotoxic compounds will be simultaneously controlled by the analysis of bulky DNA adducts, oxidative damage of DNA, proteins and lipids in placenta and lymphocytes isolated from maternal and umbilical cord blood. Gene expression profiles will be related to various biomarkers of exposure, effect and susceptibility frequently used in molecular epidemiology to clarify molecular bases of the observed changes.
Ministry of Industry and Trade
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Reg. number MPO 2A-1TP1/026 Title Research of a new form of liposoms conjugated to hydrophobic microparts of phtalocyanin for photodynamic therapy of malignant tumors. Duration 2006 - 2011 Main researcher Doc. RNDr. Pavla Poučková, CSc., RCD s.r.o. Co-researcher RNDr. Josef Souček, CSc. Annotation Testing of antitumor activity of preparations for photodynamic therapy in vitro using MTT test. Cultivation of various tumor cell lines suitable for photodynamic therapy in vitro.
Other
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Reg. number Other COST Action BM0801: Title Research grant EUGESMA-COST (Translating genomic and epigenetic studies of MDS and AML) from the Czech Ministry of Education. Name of the project: Studies of aberrantly methylated genes in MDS and AML patiens by methylation arrays. Duration 2010 - 2012 Main researcher RNDr. Cedrik Haškovec, CSc. Annotation Molecular analysis of epigenetic changes in AML and MDS patients for prognosis, progression and monitoring of treatment of the patients. Comparison of methylation in promotor parts of selected genes at diagnosis and during treatment of AML and MDS patients. Methods: DNA methylation arrays, bisulfite sequencing, methylation-specific PCR in real-time.
IHBT, Prague, Czech Republic; tel.: (+420) 221 977 111, fax: (+420) 224 913 728
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