Projects / Programmes
Comparative genomics and genomic biodiversity
January 1, 2015
- December 31, 2019
| Code |
Science |
Field |
Subfield |
| 4.02.00 |
Biotechnical sciences |
Animal production |
|
| 4.06.00 |
Biotechnical sciences |
Biotechnology |
|
| Code |
Science |
Field |
| B001 |
Biomedical sciences |
General biomedical sciences |
| Code |
Science |
Field |
| 4.02 |
Agricultural and Veterinary Sciences |
Animal and Dairy science |
comparative genomics, obesity, host-pathogen interactions, population genetics, integratomics, innate immunity, complex traits, genetic disorders
Researchers (43)
Organisations (2)
Abstract
The proposed program builds on the comparative genomic approach and on application of modern methods for the study of vertebrate genomes with the aim of detecting genetic mechanisms that shape complex traits. The special feature of the program is that connects research on animal genomes with research in human genetics and enables the development and use of animal models for the study of complex traits in humans, including the diseases with a complex genetic background. Well-documented genetic diseases in humans represent a rich source of information for studying the genetic background of diseases with similar pathology in animals. This interdisciplinary dimension of the program and the possibility of using model organisms represents nationally and internationally an innovative strategy that allows to take advantage of large amounts of high-quality genomic data and of the possibility of using an experimental approach involving model organisms.
The program is structured in five modules that complement each other and allow complex approach to the study of associations between genotype and phenotype :
1.Search associations between genetic markers and complex phenotypes
2 Functional genomics and development of animal models
3 Host – pathogen interaction
4 Bioinformatics - integratomics
5 Population studies and genomic biodiversity
In addition to modern methods for the analysis of the genomes the program also includes further development of the expertise for production of transgenic animal models using TALEN and CRISPR/Cas9 technology. In addition to the mouse model, the program includes the zebrafish as an alternative model for monitoring the development of phenotypic traits. Strong and innovative bioinformatic block based on integratomics, connects all program modules and enables the efficient exploitation of advantages offered by the comparative genomic approach. The program with the topic covering host-pathogen interactions connected to the network of excellence EADGENE .
Significance for science
The development of appropriate models for the in vitro study of cell response to infection by pathogenic micro-organisms is important contribution to the research infrastructure. because it allows us to study the interactions between host and pathogens in a standardized environment with sufficient number of repetitions, which is with the use of experimental animals virtually impossible to achieve. Model goat mammary gland epithelial cells will allow us to improve the annotation of the part of the goat genome that is involved in the development of the mammary gland and lactation. Using the comparative approach we expect to be able to improve the annotation also in the homologous part of the bovine genome.
Examining the interaction of avian mycoplasmas with the host gives us a good model to better understand the infection and the host response at the molecular level. As we first showed that M. synoviae protease cleaves the host IgG and thus ensure the persistence in the immunocompetent host. The Fc portion of IgG, which occurs as a cleavage product, represents a rheumatoid factor, which is accompanied by joint inflammation after infection with M. synoviae. Autoantibodies that have been shown in most of the samples of synovial fluid in the joints, infected with M. synoviae indicate autoimmune character of these infections. The model of arthritis caused by M. synoviae, is in many aspects similar to a human rheumatoid arthritis. In the experiments with chicken embryos infected with M. synoviae, we found that in addition to the modified responsiveness to cytokines and chemokine the change of some metabolic pathways was observed. Thus, increased transcription of the gene for citrulinaze leads to an accelerated separation from arginine, and thereby exposing new epitopes to the cells of the immune system, leading to the formation of autoantibodies These results will in the future contribute to a better understanding of autoimmune diseases caused by infection. Thymic epithelium cell line core, which expresses the protein AIRE will allow us to more precisely define the role of this protein in the maturation of the immune response.
The development of conditional transgenic models for gene Cyp51 showed that complete annihilation of CYP51 cause arrest of the embryonic development , which this model qualifies for the study of Antley - Bixler syndrome in humans. Thus, we succeeded to contribute a new model for the study of the syndrome, which causes prenatal respectively neonatal mortality in humans and has similar phenotype in mouse. Development of new models for metabolic syndrome and other diseases will be an important contribution to the research community and will allow planing of better -designed experiments .
Research on molecular base of human diseases is an important contribution to the knowledge of the presence of genetic diseases in the Slovenian population and at the same time complements the results of studies in other populations. Our group succeeded to describe the first example of cytogenetic evidence, Der ( 1 , 16 ) ( q10 , p10 ), causing acute myeloid leukemia in a woman. Using new advanced methods for the detection of structural changes in the genome we can contribute to a better understanding of the links between chromosome abnormalities and various pathologies.
The program block dedicated to the study of biodiversity will give us a better insight into the natural and breeding populations and will open new opportunities for their sustainable management. The knowledge about the genetic structure of populations is also essential for the utilization of genetic resources in breeding strategies.
Significance for the country
Importance of the program for development of Slovenia can be divided into contribution to the introduction of new technologies to keep up with the development of individual areas of genomic research and practical contribution to specific areas of research.
For the introduction of new technologies is important application of next-generation sequencing, the study of the nature of the stem cells, the development of research in the field of host pathogen interaction. These results allow us to introduce new software tools that are necessary for processing a large amount of data. Enforcement of bioinformatic approach allows us to exploit the data in different databases, and thus the performance of studies that go beyond our experimental possibilities. These applications enable us and a broader national scientific community to maintain contact with the extremely rapid technological development in the field of genomics and provide a basis for high quality teaching. Development of new animal and cell models on the one hand offers better models for the study of complex phenotypes, on the other hand, through the international exchange of these models increases the visibility and presence of our science in global science.
In certain fields, the contribution of our research is mainly at the level of the expansion of the knowledge base, which open up new possibilities for applications in many areas. Thus, the study of the biology of lactation is the basis for the identification of informative markers for selection of domestic animals and preservation of animal genetic resources. At the same time enable us to improve the health of the mammary gland and thus provide a basis for comparative studies that have practical value in the development of new diagnostic methods and improving the health status of domestic animals, which is one of the important objectives in the context of agricultural research. The results of the study of interactions between pathogens and hosts have direct practical value in the diagnostics and development of new therapeutic agents, while significantly contribute to improving the health of people and animals. Examining the genetic structure of wild populations is an important contribution to the conservation of biological diversity and provides contemporary approaches to the management of populations of wild species. Development of new, specific markers, informative for specific populations significantly contributes to the understanding and conservation of biodiversity in Slovenia. Understanding the molecular basis for the development of obesity, one of the major health problems in the Slovenian population, represents an important contribution to the search for the complex causes of obesity and the increased risk of developing cardiovascular disease, diabetes and other obesity- related diseases. The activities of our program group in the field of medical genetics represents a direct contribution to the implementation of new methods in diagnostics of important diseases and thereby improve the level of health care in Slovenia. In this way we ensure the rapid transfer of effective diagnostic tools in the domestic environment and the effective use of high-performance and technologically demanding procedures in clinical practice. Managing new technologies enables the development of commercial applications paving the way for the emergence of high technology companies.
Most important scientific results
Annual report
2015,
interim report,
final report
Most important socioeconomically and culturally relevant results
Annual report
2015,
interim report,
final report
