Functional Genomics
Doc. Dr. Radislav Sedláček, Ph.D

Doc. Dr. Radislav Sedláček, Ph.D — Program head

Functional Genomics

The genomes of humans, mice and many other species have been completely sequenced; nevertheless the knowledge of genome sequences as such does not shed light on questions concerning the functions of these sequences. Among the unanswered questions are those regarding the functions of most of the genes that encode proteins; the number of these genes is estimated to be 20 000. In order to describe biological functions of a gene, an informative modification (mutation, for instance a conditional deletion) must be inserted into the genes.

In order to annotate the function of human genes, functional (pheno)genomics needs to be combined with comparative genomics – the function of the human genome should be inferred from the function of an orthologous genetic product, e.g. from the mouse.

In recent years, mouse and rat models have been considered excellent models in the search for functions of genes within complex organisms as most of their physiological functions are very similar to those of humans and, also, their genetic differences are minimal (in comparison to other non-mammalian models). Although characterization of the function of a particular gene product (i.g. protein) in vitro delivers important information about molecular mechanisms, the verification of their real functions cannot be done without an intensive research at the level of complex organisms and their distinct physiological systems.

Functional genomics research program is based on previous work of a few research groups that have built up a substantial expertise and have already attained considerable scientific results in this field.

Goals

Supported from a robust and standardized phenotyping platform offering a functional screening of almost all physiologic body systems, the groups of this program aim to identify and characterize genes representing new potential targets to treat various human diseases. Main effort focuses on metabolic syndrome and physiologic functions interrelated with this complex human disease. Identified genes and genetic determinants will be then scrutinized for their potential to employ them as therapeutic targets. Beside the liver and metabolic disorders, research projects will focus also on visual and auditory systems whose correct functions is of enormous importance for human’s life quality and well-being. Genes important for the physiologic systems will be identified, examined, and prove whether they could serve as a diagnostic markers or therapeutic targets. Once the therapeutic potential is proved researches will together with drug developing groups or companies study the drug efficacy employing the know-how, capacity, and experimental models of the CCP.

Research projects

01
Doc. Dr. Radislav Sedláček, Ph.D

Laboratory of Transgenic Models of Diseases

02
Prof. MUDr. Jiří Forejt, DrSc.

Mouse molecular genetics

03
RNDr. Martin Gregor, Ph.D

Mouse models for studying of physiology and pathophysiology of digestive epithelia

04
RNDr. Jiří Popelář, Csc.

Auditory Function in Mutant Mice

05
RNDr. Zbynek Kozmik , CSc.

Conditional Mice Mutants as Tools for Studying Genetic Disorders and Eye Physiology

06
Doc. Mgr. Pavel Stopka, PhD.

Lipocalins in Modulation of Mammalian Reproduction

07
PhD. Lukáš Čermák

Genetically modified mice as a toll to study renewal and neoplastic transformation of gastrointestinal epithelia

08
Ing. Zdeněk Trachtulec, Ph.D

Molecular mechanisms of germ cell development

09
Prof., RNDr. Pavel Hozák, DrSc.

Epigenetics of the Cell Nucleus

10
Prof. MUDr. Tomáš Stopka, Ph.D.

Mechanisms involved in remodeling of chromatin structure during cell fate decisions

Functional Genomics

Publications

2017

Youngson N.A., Epp T., Roberts A.R., Daxinger L., Ashe A., Huang E., Lester K.L., Harten S., Kay G.F., Cox T., Matthews J.M., Chong S. and Whitelaw E.: No evidence for cumulative effects in a Dnmt3b hypomorph across multiple generations. 2013. Mammalian Genome.

Bhattacharyya T, Gregorova S, Mihola O, Anger M, Sebestova J, Denny P, Simecek P, Forejt J.: Mechanistic basis of infertility of mouse intersubspecific hybrids. Proc Natl Acad Sci U S A. 2013 Jan 17.

2016

Kasparek P, Krenek P, Buryova H, Suchanova S, Beck IM, Sedlacek R: Transgenic mouse model expressing tdTomato under involucrin promoter as a tool for analysis of epidermal differentiation and wound healing. Transgenic Res 201221(3): 683-9. [pubmed] [doi]

Fafilek B, Krausova M, Vojtechova M, Pospichalova V, Tumova L, Sloncova E, Huranova M, Stancikova J, Hlavata A, Svec J,Sedlacek R, Luksan O, Oliverius M, Voska L, Jirsa M, Paces J, Kolar M, Krivjanska M, Klimesova K, Tlaskalova-Hogenova H,Korinek V: Troy, a Tumor Necrosis Factor Receptor Family Member, Interacts With Lgr5 to Inhibit Wnt Signaling in Intestinal Stem Cells. Gastroenterology 2012. [pubmed] [doi]

Jirouskova M, Zbodakova O, Gregor M, Chalupsky K, Sarnova L, Hajduch M, Ehrmann J, Jirkovska M, Sedlacek R: Hepatoprotective Effect of MMP-19 Deficiency in a Mouse Model of Chronic Liver Fibrosis. PLoS One 2012 7(10): e46271. [pubmed] [doi]

Contact

Ústav molekulární genetiky AV ČR, v. v. i.
Vídeňská 1083, 142 20 Praha 4
Česká republika