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PhD topics for academic year 2021/2022

Department of Informatics and Chemistry

Bioinformatics

Faculty of Chemical Technology

Genetic recombination and reproductive isolation on Mus musculus model

Forejt Jiří, prof. MUDr. DrSc.
Kolář Michal, Mgr. Ph.D. ( kol...@img.cas.cz)
he aim of the proposed dissertation project is to elucidate the epistatic interaction of the PRDM9 histone methyltransferase gene with the X-linked Hstx2 genetic factor in meiotic recombination and male infertility of intersubspecific hybrids. Our laboratory identified the Prdm9 as the first gene in vertebrates engaged in reproductive isolation between species. PRDM9 protein predetermines the meiotic recombination hotspots within species to ensure meiotic cross-overs, chromosome pairing and differentiation of germ cells, but in intersubspecific hybrids the same gene product causes meiotic arrest and hybrid sterility due to persistence of DNA double-strand breaks, recombination failure and subsequent failure of chromosome pairing. The process is modulated by the Hstx2 genetic factor, localized in a 2.7 Mb interval on the chromosome X. The main task of the project is to identify the genomic sequence responsible for the Hstx2 effect using a panel of bioinformatics tools for mRNA expression profiling using next generation RNA sequencing (RNA-seq), for chromatin immunoprecipitation sequencing (ChIP-seq) and for quantitative trait loci (QTL) mapping.
Institute of Molecular Genetics of the CAS, v. v. i.
Faculty of Chemical Technology

Genome-wide mapping of loci forming genotoxic intermediates associated with collisions between replication and transcription complexes

Dobrovolná Jana, RNDr. Ph.D. ( jan...@img.cas.cz)
Kolář Michal, Mgr. Ph.D. ( kol...@img.cas.cz)
Recent studies have shown that in human precancerous lesions, activated oncogenes induce stalling and collapse of replication forks, leading to genomic instability, a driving force of cancer. The proposed project addresses the hypothesis that oncogene-induced replication stress arises from interference between transcription and replication, which is associated with the formation of genotoxic RNA:DNA hybrids, referred to as R-loops. The project has the following objectives: (i) to identify on genome-wide scale the loci that are prone to R-loop formation under conditions of oncogene-induced replication stress; (ii) to determine basic charateristics of these loci; (iii) to assess whether oncogene activation is associated with R-loop formation at common fragile sites that are preferred target of oncogene-induced replication stress; (iv) to dermine whether R-loop forming loci overlap with the breakpoints of chromosomal rearangements found in cancers.
Institute of Molecular Genetics of the CAS, v. v. i.
Faculty of Chemical Technology

Integration of phenotyping and functional genomic data

Novosadová Vendula, Ing. Ph.D. ( ven...@img.cas.cz)
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.
Institute of Molecular Genetics of the CAS, v. v. i.
Faculty of Chemical Technology

Biological machine learning

Pluskal Tomáš, Ing. Ph.D. ( tom...@uochb.cas.cz)
Our lab combines cutting-edge experimental (e.g., LC-MS, metabolomics, RNA-seq) and computational (e.g., bioinformatics, molecular networking, machine learning) approaches to develop rapid, generally applicable workflows for the discovery and utilization of bioactive molecules derived from plants. We are looking for talented and motivated computational researchers to join our team. The successful candidate for this position will be developing models for the prediction of enzymatic activities of enzymes in biosynthetic pathways. Owing to the interdisciplinary nature of the lab, this project will be conducted in close collaboration with experimental researchers who will be generating data for model training and verification.
Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Faculty of Chemical Technology

Computational mass spectrometry

Pluskal Tomáš, Ing. Ph.D. ( tom...@uochb.cas.cz)
Our lab combines cutting-edge experimental (e.g., LC-MS, metabolomics, RNA-seq) and computational (e.g., bioinformatics, molecular networking, machine learning) approaches to develop rapid, generally applicable workflows for the discovery and utilization of bioactive molecules derived from plants. We are looking for talented and motivated computational researchers to join our team. The successful candidate for this position will be developing the next generation of the MZmine platform (https://mzmine.github.io) for mass spectrometry data processing in metabolomics. Among other things, we are aiming to add full support for ion mobility spectroscopy (IMS) to MZmine, and to enhance its molecular networking capabilities. Experience with Java programming is recommended.
Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.
Updated: 11.12.2019 11:36, Author: Jan Kříž

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