Projects solved in year 2009
Choose a year when a project is solved and a founder:
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 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. -
Reg. number GA CR GA206/08/1587 Title Migrations by infiltrations and its impact on genetic structure: the population history of nomadic versus sedentary populations of the African Sahel Duration 2008 - 2010 Main researcher Mgr. Viktor Černý, Dr., Archeologický ústav AV ČR, Praha, v. v. i. Co-researcher Prof. MUDr. Radim Brdička, DrSc. Annotation The aim of this project is to detect still insufficiently investigated genetic consequences of mutual contacts of the sedentary and nomadic human populations. The fundamental role will be played by separate and geographically different groups of the Fulani herders dispersed in the African Sahel. Their mutual contacts with neighbouring agricultural populations are relatively well documented by ethnography, linguistics, and archaeology. Similarly as the findings about relationships of hunter-gatherer and farmer populations our results could serve as a model of past infiltrations which were important demographic events from the Neolithic (post-colonization) period onwards. If the infiltration/admixture of sedentary populations is realised only (or predominantly) by the nomadic girls on a long-term period scale and not only at the level of our own generation visibility we can expect a reduced mtDNA diversity of the nomadic groups in comparison with that of their sedentary neighbours. The -
Reg. number GA CR GP301/08/P154 Title The miRNA expression diversity study in chronic myelogeneous leukemia Duration 2008 - 2010 Main researcher Mgr. Kateřina Machová Poláková, Ph.D. Annotation Chronic myelogeneous leukemia (CML) is a malignant disorder caused by abnormal function of fusion protein BCR-ABL as the consequence of reciprocal translocation t(9;22) (q34;q11). A great progress in CML treatment was achieved by tyrosine kinase inhibitor, imatinib. However, the resistance or suboptimal response to treatment appeared in some patients. CML is clinically heterogeneous disorder. The molecular basis for this clinical heterogeneity is unclear. MiRNAs are small non-coding RNA regulating gene expression. During cell development and differentiation, miRNA is tightly regulated in tissue specific manner. Aberrant expression of specific miRNAs has recently been described mainly for chronic lymphocytic leukemia (CLL). The aim of the proposed project is to reveal specific miRNAs, which contribute to pathogenesis and heterogeneity of CML. -
Reg. number GA CR GA204/07/0830 Title Iron metabolism and cellular cytoskeleton: defining a new role for MRCKα Duration 2007 - 2009 Main researcher MUDr. Daniel Vyoral, CSc. Annotation Iron is an indispensable element for human body. However, iron can also catalyze the formation of free radicals, which are able to initiate pathogenesis of numerous diseases (atherosclerosis, inflammations, cancer). Human diseases resulting from disorders of iron transport and storage are common (hemochromatosis, anemias), unfortunately these processes are incompletely understood.In our laboratory we described a novel iron-mediated regulation of the kinase MRCKα. According to our working hypothesis, this protein regulates endocytosis of a key cellular iron donor - transferrin.In this project we will elucidate the mechanisms by which MRCKα regulates endocytosis. We will describe the relationship between expression of MRCKα and the amount of cellular iron. We will find MRCKα associated protein partners and will identify target proteins phosphorylated by MRCKα. The understanding of the detailed role of MRCKα in mechanisms of endocytosis will broaden our knowledge in iron metabolism and will bring a better treatment of the disorders of iron transport and storage.
Internal Grant Agency of the Ministry of Health
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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 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. -
Reg. number IGA MH NS10633-3/2009 Title Posttranslation protein modifications in activated blood platelets Duration 2009 - 2010 Main researcher Ing. Jiří Suttnar, CSc Co-researcher MUDr. Martin Malý, PhD., Fakultní nemocnice v Motole Annotation The aim of the project is identication of posttranslation modifications (PTM) in proteins of both activated and non activated platelets with a special fokus on redox-dependent protein modifications. The platelets will be activated by various agonists. The basic proteomics tools will be both electrophoretic and chromatographic separation methods together with mass spectrometry. The obtained data should help in understanding the biological effects of RONS in hemostasis. -
Reg. number IGA MH NR9227 Title Molecular cytogenetic analysis of complex chromosomal aberrations in bone marrow cells of patients with myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML) and AND its contribution for prognosis. Duration 2007 - 2009 Main researcher RNDr. Zuzana Zemanová, CSc., Všeobecná fakultní nemocnice v Praze Co-researcher RNDr. Jana Březinová, Ph.D. Annotation Molecular cytogenetic analysis of complex chromosomal aberrations in patients with MDS and AML. Identification of chromosomes and/or chromosomal regions involved in complex karyotypes. Evaluation of the impact of complex rearrangements on prognosis of the patients. -
Reg. number IGA MH NR9235 Title INVESTIGATION OF GENE EXPRESSION PROFILING IN PATIENTS WITH MYELODYSPLASTIC SYNDROME Duration 2007 - 2009 Main researcher MUDr. Jaroslav Čermák, CSc. Co-researcher Mgr. Monika Beličková Annotation 1. Analysis of gene expression profile in MDS patients using cDNA microarray assay . Investigation of mutation status of proliferation genes and by determination of methylation status of differentiation genes. 2. Comparison of results obtained by gene expression profiling with results of clonality assay, measurement of telomere length and with karyotype analysis using molecular cytogenetics methods as well as with clinical data. 3. Determination of valid prognostic factors on the base of results of molecular genetics methods contributing to identification of a subgroup of risk patients with early MDS and potentially adverse outcome which should be indicated for stem cell transplantation. 4. Usefulness of a complex of molecular genetics methods for evaluation of clonal remission after chemotherapy or after administration of drugs targeting methylation status of differentiation genes or activity of proliferation genes. -
Reg. number IGA MH NR9236 Title Endogeneous post-transcriptional regulation of gene function by miRNA Duration 2007 - 2009 Main researcher RNDr. Hana Bruchová, PhD. Annotation The project is based on our previous research study, in which using siRNA-mediated gene silencing we analyzed possible function modulation of the genes whose dysregulation was associated with various onco-hematological processes. In contrast to siRNAs, this project is focused on miRNA analyses that also allow to observe de-repression of gene function using miRNA inhibitors. The project includes: 1) miRNA expression profiling in cell lines and in peripheral blood cells of healthy persons using microarrays; 2) analyses of gene activity changes after inhibition of selected miRNAs using Anti-miRNAs at both transcriptional and translational level. In this study we will use cell lines K562, KU812, MOLM7, HL60, HEL and total peripheral blood leukocytes obtained from healthy donors, eventually monocytes and granulocytes or cell subtypes CD34+, CD14+, CD3+ will be used. Expression of miR15, miR16, miR142, miR155 and miR223 will be monitored in hematopoiteic cells. -
Reg. number IGA MH NR9238 Title Vectors for gene therapy targeted on stromal cells of solid tumors Duration 2007 - 2009 Main researcher RNDr. Šárka Němečková, DrSc. Annotation Investigation of an anti-tumor therapeutic DNA vaccine and vectors for gene therapy targeting tumor fibroblasts in mouse model of tumors induced by papilloma virus HPV16. DNA vaccine will provide immunization against fibroblast activating protein (FAP). Vaccine will be combined with DNA vaccine specific for viral oncoprotein HPV16-E7. Recombinant vaccinia virus vectors will allow expression of the ectodomain of the human type II TGF-beta receptor genetically fused to the IgG1Fc fragment or the gene for IGFBP-3 (IGF Binding Protein-3). Immunotherapy with DNA vaccines and viral vectors expressing the anti-tumor factors and immune response enhancing cytokines resulting in increase of the anti-tumor mechanisms. -
Reg. number IGA MH NR9243 Title Study of the disturbancies of cell adhesion regulation in hematological malignancies Duration 2007 - 2009 Main researcher RNDr. Zbyněk Hrkal, DrSc. Annotation The adhesive properties of leukemia cells and cell lines derived from chronic myelogenous leukemia (CML) K562, JURL-MK1, to the extracellular matrix compounds (fibronectin, collagen, laminin, vitronectin) will be studied. Using differential proteomic analysis the mechanism will be studied of the effects of inhibitors of BCR-ABL tyrosine kinase activity, of proteasome, HSP90 chaperonic activity and histone deacetylases, on the proteins of CML cells adhesion apparatus. By means of interaction proteomics the signaling pathways will be identified which are responsible for defective adhesion of CML cells, and the molecular mechanism would be derived of the effects of the above substances on the adhesive properties. -
Reg. number IGA MH NR9244 Title Combined molecular biology and molecular cytogenetic analysis of genomic changes in patients with chronic lymphocytic leukemia Duration 2007 - 2009 Main researcher RNDr. Jana Březinová, Ph.D. Annotation Annotation I: Detection of specific genomic aberrations in patients with B-CLL using molecular cytogenetic methods, assessment of the telomere length and hTERT gene expression profile. Annotation II: Correlation of molecular cytogenetic and molecular genetic results with IgVH mutation status, morphological and immunophenotypical parameters and their prognostic significance. -
Reg. number IGA MH NR9246 Title Development of anti-tumor DNA vaccines based on fusion of immunogen with E. coli beta-glucuronidase and enhancement of their effect by stimulation of non-specific immunity Duration 2007 - 2009 Main researcher RNDr. Michal Šmahel, PhD. Annotation Enhancement of efficacy of therapeutic anti-tumor vaccines based on fusion of a tumor antigen with E. coli beta-glucuronidase. Increase of production of immunogens (oncoproteins E7 and E6 of HPV16 and fusion oncoprotein Bcr-Abl) by modification of genes. Determination of mechanisms involved in induction of immune reactions after administration of fusion genes intradermally by a gene gun or intramuscularly by injection. Examination of immunization effects in mouse tumor models. Enhancement of anti-tumor efficacy of DNA vaccines by combination of single fusion genes and by combination with drugs stimulating innate immunity, particularly via Toll-like receptors. Elimination of tumor cells with different mechanisms of escape from the host immunity, especially down-regulation of MHC class I surface expression and mutation of the immunodominant epitope of a tumor antigen. -
Reg. number IGA MH NR9258 Title Thrombocytopenic microangiopatic disorders - etiology, pathofysiology and diagnostic Duration 2007 - 2009 Main researcher RNDr. Ingrid Hrachovinová Annotation We will study molecular-genetic of atypical HUS: establish an assay for measurement of factor H, screen mutations in gene for factor H and look for other possible causes of disease. We will study relationship of ADAMTS13 and BMT-associated TMA, its treatment and other causes of microangiopatic syndromes. -
Reg. number IGA MH NR9418 Title Utilisation of genetical analysis to the diagnostics of human cytomegalovirus infection in immunodeficient patients Duration 2007 - 2009 Main researcher RNDr. Kateřina Roubalová, CSc., Státní zdravotní ústav Co-researcher MUDr. Antonín Vítek Annotation A) Genotyping of CMV strains identified in clustered cases of CMV infection in hematopoietic stem cell transplant recipients treated in Inst.Hematol. Blood Transfussion during the period 2004-5 using methods of RFLP analysis of gB gene UL55 and sequenation of N- terminal fragment of gN gene UL73.Subsequent epidemiological analysis of the infections. B) Setting of the methods for detection of antivirals resistence-associated CMV mutants by genetical analysis of UL97 and UL54 and their use for characterisation of CMV strains obtained from patients with poor response to antiviral therapy. -
Reg. number IGA MH NR9466 Title Use of virologic markers in the treatment and prevention of oral and oropharyngeal cancer Duration 2007 - 2009 Main researcher Doc. MUDr. Jan Klozar, CSc., Fakultní nemocnice v Motole Co-researcher RNDr. Ruth Tachezy, PhD. Annotation The study will verify the differences between the group of patients with HPV positive and negative oral/oropharyngeal tumors from the clinical point of view. The results of the project will contribute to earlier diagnosis especially of recurrences and more precise follow-up after treatment by means of molecular biological and serological methods. They could also influence the choice of optimal method and intensity of the treatment. Introduction of a biomarker for early diagnosis of these tumors would have substantial benefits. Results of our study will be an important contribution to the growing body of knowledge on the possible role of HPV as an etiological factor of oropharyngeal and oral cancer. The study also finds out the HPV type specific prevalence in the Czech population, which represents valuable information for the future vaccination. It also enables to specify the number of patients with HPV associated head and neck tumors in the Czech Republic. -
Reg. number IGA MH NR9481 Title The optimalization of expensive examination and treatment procedures aimed at the augmentation of treatment effectiveness and mortality reduction in AML patients based on clinical and high-sophisticated predictive data and its multifactorial analysis Duration 2007 - 2009 Main researcher Prof. MUDr. Karel Indrák, DrSc., Univerzita Palackého v Olomouci Co-researcher MUDr. Jacqueline Maaloufová Annotation I. Evaluation of known and newly detected prognostic factors in AML using hematologic, cytogenetic and molecular genetic methods, follow up the response to various kind of induction and consolidation treatment with special focus on hematopoietic cells transplantations. II. Keeping continuity in reporting AML patients data to ALERT database immediately after the diagnosis assignment and during the follow up; to evaluate minimal residual disease in complete remission in patients according to molecular genetic marker availability. III. Performance of statistical analysis of available prognostic factors with special focus on genetics and consolidation treatment strategy used in the group of 2000 patients entering the ALERT study within 1996-2009. IV. Utilising the analysis results on evaluation of quality of AML treatment in Czech republic and on creating of patients stratification treatment proposal according to prognostic factors with focus on transplantations and palliative treatment.
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.
Grant Agency of the Charles University
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Reg. number GA ChUni 257 928 928 07 Title Study of molecular mechanisms of Diamond-Blackfan anemia Duration 2007 - 2010 Main researcher Mgr. Helena Handrková Annotation Diamond-Blackfan anemia (DBA) is characterized by selective deficiency of erythroid precursors and other defects. The only causal mutation identified in DBA patients is in gene for ribosomal protein S19 (RPS19), which is altered in 25% of DBA patients. No underlying gene has been identified in the remaining 75% of pacients. It is reasonable to expect that other proteins that associate with RPS19 may be mutated in DBA patients. Our project is focused on RPS19-associated proteins and their role in DBA. As a model of DBA, we have developed human erythroleukemic cells expressing either wild-type or mutated RPS19 genes. Native complexes of RPS19 with associated proteins will be isolated via antibody immobilized on magnetic beads and composition of the complexes will be studied. Proteins that interact only with wild-type or only with mutated RPS19 will be identified by mass spectrometry. We will confirm the direct interaction of these proteins with RPS19 using another expression systems. Finally, we intend to screen patients with DBA and search for mutations in these candidate genes. Understanding of molecular basis of DBA and identification of new causal mutations will pave a way to early and more effective diagnosis and treatment of patients with DBA.
Ministry of Education, Youth and PT
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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. -
Reg. number MEYS LC06044 Title Center for Experimental Hematology Duration 2006 - 2010 Main researcher Prof. MUDr. Emanuel Nečas, DrSc, Univerzita Karlova, 1. lékařská fakulta, Ústav patologické fyziologie Co-researcher RNDr. Ludmila Doležalová, CSc. Annotation To identify and describe molecular mechanisms during normal and pathologic hematopoiesis. To integrate scientific teams from two hematologic institutions; to improve their laboratory equipment; to increase their international cooperation. To improve quality of postgraduate projects. To increase and improve publication efforts. -
Reg. number MEYS 1M0538 Title Center for Cell Therapy and Tissue Repair Duration 2005 - 2009 Main researcher Prof. MUDr. Eva Syková, DrSc., 2. lékařská fakulta, Univerzita Karlova v Praze Co-researcher MUDr. Petr Kobylka, CSc. Annotation Cell therapy provides an alternative treatment for degenerative and civilization-related diseases, including neurological. The aim of cell therapy, especially using stem cells, is to replace, repair and improve the function of damaged tissue. We will achthis aim by implanting cells into a target organ in sufficient numbers and quality to initiate functional recovery. Biocompatible hydrogels and their ability to support the recovery of damaged tissue and to increase the possibility ofregeneration forms an integral part of the project. Our aim is to perform preclinical tests and to introduce the methods used into clinical practice.
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 3502 Title Implementation and optimization of a microfuidic chip-based system to determine the level of Crkl and Src kinases phosphorylation in CML Duration 2009 - 2010 Main researcher Markéta Žáčková Annotation The main aim of this project is to implement and optimize the measurement of BCR-ABL kinase sensitivity to tyrosine kinase inhibitor on Bioanalyzer 2100 (Agilent) Lab-on-a-Chip technology.
IHBT, Prague, Czech Republic; tel.: (+420) 221 977 111, fax: (+420) 224 913 728
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