čas: 7.6.2020 10:19:51
Obnovit | RAW
Institute of Molecular Genetics of the CAS, v. v. i.
List of available PhD theses
High-throughput transcriptomics platform
The aim of the project is to develop a robust ultra-high-throughput sequencing platform and a bioinformatics pipeline for the analysis of gene expression in chemical biology and drug discovery. Platforms that are currently used in academic research and pharmaceutical development are limited by their high cost and low throughput. Therefore, we will establish a cost-effective high-throughput transcriptome profiling strategy with simplified sample preparation and multiplexing in 384/1536-well format. The transcriptional profiles will be correlated with the Mechanism of Action (MoA) of the analyzed compounds, which will facilitate mechanistic studies of novel compounds and their biological activities. The scheme can be combined with the CRISPR gene-editing methods to enable the discovery of gene functions in cells and organisms.
Integration of phenotyping and functional genomic data
The position of bioinformatician is becoming necessary for every scientific group. Generating large datasets of omic data makes it necessary to develop new computational algorithms using tools such as machine learning and artificial intelligence, which will also allow the processing of diverse unstructured data. Our group is part of the research infrastructure Czech Centre for Phenogenomics, involved in the systematic annotation of the mouse genome within the International Mouse Phenotyping Consortium (IMPC). We produce mouse lines with one gene deactivated. These lines are further characterized by a standard phenotyping pipeline. The data set from each animal tested has over 700 parameters from different fields. These parameters contain numeric, categorical and image data. We are also collecting metabolomic data for selected lines. The Ph.D. project aims to integrate every data generated both in our center and within the whole IMPC. Linking individual parameters and finding correlations and causality between them and their possible semantic analysis will help to better understand the phenotype. At the same time, knowledge of a given gene function will enable mathematical modeling of the phenotype of genes involved in similar or overlapping regulatory networks.
The role of PRDM9 histone methyltransferase in genetic recombination and reproductive isolation between species
The Prdm9 gene determines localization of meiotic recombination hotspots in genome of mice, humans and other mammalian species. In our laboratory we discovered another function of Prdm9, as a major hybrid sterility gene responsible for infertility of hybrids between related mouse species. To verify Prdm9 as the first speciation gene in vertebrates various combinations of Prdm9 alleles will be tested by genome-wide mapping of PRDM9 hotspots and their correlation to fertility phenotypes. The optical maps at the large scale and the genomic hotspot maps of recombination will be generated by Bionano optical mapping technology and by Illumina platform based ChIP-seq technology, respectively. The aim of this PhD thesis will be, using bioinformatics tools, to analyze the acquired datasets with the perspective to get correlations between maps from mice with different phenotypes and to determine key components of genomic structure and recombination landscape crucial for hybrid sterility.