MZ ČR
MZ ČR
Individual projects of the Ministry of helth are provided of the Agency for Health Reaserch of the Czech Republic (AZV ČR), which provides targeted support in accordance with the National Policy of Research , Experimental development and Innovation of the Czech Republic.
Application of retinal cells and organoids in functional diagnostics and treatment of vision loss in Bardet-Biedl syndrome
Basic information: Inherited retinal diseases are a genetically heterogeneous group of rare eye disorders with a progressive manifestation causing vision loss, affecting approximately one in 2,000 individuals worldwide. An increasing number of genes have been associated with inherited retinal degeneration, yet the understanding of their function in retinal biology is very limited. Bardet-Biedl syndrome (BBS) is a systemic, rare autosomal-recessive ciliopathy, with a prevalence around 1:150,000 in North America and Europe. This makes BBS the most common non-lethal ciliopathy involving early onset visual impairment. Efforts have been made to develop an early intervention to treat the inherited retinal degeneration diseases including BBS, with minimal success so far. The main objective of the proposed research is to characterize the molecular pathogenesis of retinal degeneration in BBS, and to suggest a suitable pharmacological intervention. We hypothesize that the progressive photoreceptor death in BBS is a consequence of their long-term ER stress, and that identification of the involved response pathways and their pharmacological modulation may prevent the disease onset and progression. Because the mouse models do not faithfully recapitulate many characteristics of the human BBS disease, mostly due to interspecies differences, we will take advantage of the human induced pluripotent stem cell-derived retinal organoids and retinal pigmented epithelium cells in order to develop a high-throughput system for functional diagnostics of specific mutations present in BBS, and for their targeted pharmacotherapy. Cíle projektu anglicky The main objective of the proposed research is to develop a high-throughput system in order to characterize the molecular pathogenesis of retinal degeneration in BBS, and to suggest a widely applicable pharmacological intervention. The following specific aims will address the objective: 1) To generate hiPS cells carrying specific BBS mutations. 2) To characterize the ciliary defect caused by BBS mutation using hiPS cell-derived RPE cells. 3) To define the photoreceptor phenotype in retinal organoids produced from BBS hiPS cells. 4) To screen for a pharmacological treatment of BBS using retinal organoids and RPE cells. The proposed research has a clear application potential, as we aim to develop a unique screening platform, and to suggest a novel treatment for so far incurable human genetic condition.
Registrtion No: NU22-07-00380
Project duration: 1. 5. 2022 – 31. 12. 2025
Principal Investigator: Mgr. Tomáš Bárta, Ph.D. Masarykova univerzita
Other solver: Mgr. Michaela Bosáková, Ph.D. Ústav živočišné fyziologie a genetiky AV ČR, v. v. i.
Self-expandable metallic stent in the treatment of anastomotic stricture associated with Crohn's disease recurrence - an experimental randomized study
Basic information: In a large proportion of patients operated for Crohn's disease, there will be a recurrence and the development of stenosis in the area of intestinal anastomosis. Drug treatment in these cases is usually ineffective and patients need to be reoperated. New endoscopic techniques could delay or eliminate the need for rerection, thereby improving the quality of life of patients and reducing the cost of treatment. The expected benefit of the project is an experimental evaluation of the effect of introducing a self-expressed stent into the site of stenosis in recurrence of Crohn's disease in the field of enterocolic anastomosis, including the design of a functional therapeutic algorithm. During the project, the potential of endomicroscopy in evaluating the effect of endoscopic treatment will be further evaluated. The project supports the development of new minimally invasive techniques with the aim of reducing the risk of postoperative complications and reducing the need for hospitalization by transferring treatment to an outpatient regimen.
Registrtion No: NU22-08-00554
Project duration: 1. 5. 2022 – 31. 12. 2025
Principal Investigator: MUDr. Ondřej Ryska, Ph.D. Ústav živočišné fyziologie a genetiky AV ČR, v. v. i.
Identification of changes in glutamatergic pathways specific for sporadic form of Alzheimer's disease in human neurons and astrocytes induced from patient's cells
Basic information: Suitable procedures for studying early pathology of Alzheimer's disease (AD) are currently being sought. The main aim of the project is to create a model of cell cultures suitable for monitoring changes in the biology of nerve cells (neurons and astrocytes) in patients with AD. Using the induced pluripotent cell method (iPSC), the role of nerve cells in the formation of sporadic form of AD will be studied. IPSCs are the ideal model, because they can be derived from any individual; they are genetically identical to the donor; and they have the capacity to form any cell type. Differentiation of fibroblast-derived human iPSCs into mature nerve cells affects the expression of ion channels and receptors that could play a crucial role in the formation of AD. The main aim of the project is to identify changes in glutamatergic pathways in human astrocytes induced from cells of patients with sporadic AD. Our results will help reveal the mechanisms responsible for astrocytic impairment in AD patients, and suggest an effective strategy for its treatment and prevention.
Registrtion No: NU20-09-00437
Project duration: 1. 5. 2020 – 31. 12. 2023
Principal Investigator: doc. RNDr. Alexandr Chvátal, DrSc., MBA Univerzita Karlova / Lékařská fakulta v Plzni
Other solver: MUDr. Jiří Hudeček Fakultní nemocnice Plzeň
Other solver: doc. Mgr. Jan Lochman, Ph.D. Ústav živočišné fyziologie a genetiky AV ČR, v. v. i.
Basic information: Tooth ankyloses are pathological conditions in human, which arise by direct fusion of the tooth with surrounding tissues as a result of trauma or inflammation around teeth. Failure of interaction between these tissues lead to the disruption of tooth function as an organ and the resorption of alveolar bone. This state is followed by loss of teeth and by the initiation of conditions inappropriate for following teeth reconstruction. Aim of the project is to uncover cellular and molecular processes contributing to morphological and functional changes during tooth ankyloses initiation in human. Project will use new methodical approaches such as LIBS, micro CT examination or gene expression analyses of osteogenic factors in periodontal area with aim to expand our understanding about causes of teeth ankyloses commencement as well as possibilities of new approaches for their prevention during teeth traumas.
Registrtion No: NU20-06-00189
Project duration: 1. 5. 2020 – 31. 12. 2023
Principal Investigator: doc. RNDr. Marcela Buchtová, Ph.D. Ústav živočišné fyziologie a genetiky AV ČR, v. v. i.
Other solver: MUDr. et MUDr. Jan Štembírek, Ph.D. Fakultní nemocnice Ostrava
Other solver: Prof. MUDr. Lydie Izakovičová Hollá, Ph.D. Fakultní nemocnice u sv. Anny v Brně
Basic information: Infections affecting the root canal of the tooth are the most common cause of apical periodontitis (AP). Chronic inflammation in the periodontium may lead to the development of a radicular cyst (RC), a type of inflammatory odontogenic cyst (OC). OC of developmental origin also includes dentigerous cysts (DC) and odontogenic keratocysts (OKC). Correct classification of OCs reflecting their etiopathogenesis including genetic factors is crucial for choosing an optimum therapy and patient management. The aim of the project is to identify risk factors of OC development and improve their diagnosis. The project includes study of microbiome present in the root canal, genetic association studies focused on patients´immune profiling and influence of genes envolved in odontogenesis, comparative studies of gene expression profiles in various types of odontogenic cysts, and study of selected molecular pathways in OC pathogenesis in an animal model. Based on the obtained results we will propose a panel of markers for prediction of OC development and differential diagnosis of OC types.
Registrtion No: NU20-08-00205
Project duration: 1. 5. 2020 – 31. 12. 2023
Principal Investigator: doc. RNDr. Petra Bořilová Linhartová, Ph.D., MBA Masarykova univerzita, Lékařská fakulta
Other solver: MUDr. et MUDr. Zdeněk Daněk, Ph.D. Fakultní nemocnice Brno
Other solver: doc. RNDr. Marcela Buchtová, Ph.D. Ústav živočišné fyziologie a genetiky AV ČR, v. v. i.
Rationalisation of ATB Therapy in Diabetic Foot Infection and its Impact on the Intestinal Microbiota
Basic information: Infectious complications associated with diabetic foot(DF) not only increase the morbidity of DF patients,but also the economic demands arising from hospitalisations and amputations.Instances of amputation due to DF infection can be prevented by administering antibiotic(ATB)therapy at levels conducive to optimal bactericidal activity in serum and tissue.However,time-dependent ATBs are not routinely monitored in DF patients.The aims of this project are to analyse the serum and tissue concentrations of beta-lactam and cephalosporin ATBs administered under different dosing regimens, and to evaluate bactericidal and clinical effects on parameters of infection in DF patients at various stages of peripheral arterial disease.We will monitor ATB effects on the gastrointestinal tract(GIT),particularly changes in the microbiota and intestinal barrier,while determining the optimal ATB dosing regimens required for increasing microbicidal effects and reducing GIT side-effects.Our study introduces a novel approach to preventing infection progression and reducing amputation rates in DF patients.
Registrtion No: NU20-01-00078
Project duration: 1. 5. 2020 – 31. 12. 2023
Principal Investigator: MUDr. Vladimíra Fejfarová, Ph.D. Institut klinické a experimentální medicíny
Other solver: Ing. Jakub Mrázek, Ph.D. Ústav živočišné fyziologie a genetiky AV ČR, v. v. i.
