PhD Programme

Research topics: Chemical genetics, haematopoietic and neural cell differentiation, signalling pathways, nuclear receptors

The main interest of the laboratory lies in the molecular mechanism of cell fate determination. In the lab we have established in vitro systems to study the self-renewal and differentiation of haematopoietic, neural and mesenchymal stem cells. We use growth factors and small molecules as tools to manipulate these systems. More recently, we have initiated more systematic search for such tools using chemical biology/genetics approaches.

Candidate’s profile (requirements):
MSc or equivalent in molecular and developmental biology.

PhD project:
Dissecting hematopoietic development using zebrafish model

Supervisor: Petr Bartůněk (bartunek@img.cas.cz)

PhD Project:
Nuclear receptors in normal and cancer cells: Identification of new ligands

Supervisor: Petr Bartůněk (bartunek@img.cas.cz)

PhD Project:
Mouse transgenic models for sterol-sensing domain containing proteins

Supervisor: Petr Bartůněk (bartunek@img.cas.cz)

The Laboratory of Leukocyte Signaling is studying the molecular mechanisms of signal transduction in leukocytes. Our interest has recently been focused on the regulation of Src-family kinases by Csk and by receptor tyrosine phosphatases and on the role of Csk compartmentalization in the process, but the data we generate also lead us to other areas of signal transduction research. Src-family kinases are tightly controlled enzymes critically involved in the signaling via a number of leukocyte surface receptors such as T cell and B cell antigen receptors.

Candidate’s profile (requirements):
M.Sc. or equivalent in immunology, molecular biology or related field.

PhD Project:
The project will be focused on the negative regulation of leukocyte surface receptor signaling by transmembrane adaprtor proteins. It will include an analysis of mice and cell lines deficient in the expression of two novel transmembrane adaptor proteins LST1/A and OPAL1 known to recruit various inhibitory molecules to the proximity of the plasma membrane. The work will also include a biochemical and structure-function analysis of these adaptors. During the course of the project the student will acquire a wide range of techniques required for the analysis of murine immune system functions at the organismal level, as well as methods employed in the molecular and biochemical analysis of cellular signaling.

Supervisor: Tomáš Brdička (tomas.brdicka@img.cas.cz)

Laboratory of Biology of the Cell Nucleus
www.img.cas.cz/research-groups/pavel-hozak

The nucleus contains machineries for transcription of genes and processing of RNA products, and for precise DNA replication, repair and recombination. Nuclear interior is therefore functionally highly compartmentalized, and the recent evidence points strongly to structure-related regulation of nuclear functions. Our research concentrates on: (1) the relationship between nuclear compartmentalization and regulation of gene expression, (2) structure, dynamics, and function of the nucleoskeleton, which contributes to the nuclear compartmentalization, (3) functions of nuclear myosins and actin in transcription and gene expression, (4) functions of nuclear lipids, (5) development of new microscopy methods for ultrastructural studies.  

Candidate’s profile (requirements):
M.Sc. or equivalent in molecular/cell biology, fluent in English

PhD project:
Structure of the cell nucleus related to chromatin remodelling and regulation of gene expression

Supervisor: Pavel Hozák (hozak@img.cas.cz)

The majority of tissues in the adult organism contain a population of tissue-specific stem cells. These multipotent cells are involved in homeostatic self-renewal and tissue repair processes. The biology of the stem cells is driven by a limited set of signalling cascades. The deregulation of these cascades can ultimately lead to the cellular transformation and formation of tumours. This clearly indicates the connection between the stem cell physiology and cancer. The scientific goal of the laboratory is to elucidate molecular mechanisms influencing behaviour of normal and diseased intestinal epithelial cells. Since the fate of these cells is determined by the so-called Wnt signalling pathway, our main focus is to find genes regulated by the Wnt pathway and/or encoding proteins directly involved in the signalling process.

Candidate’s profile (requirements):
M.Sc. or equivalent in molecular, cell and developmental biology or biochemistry; fluent English.

PhD project:
Title: Molecular mechanisms of tissue homeostasis and tumor formation in the intestine

The aim of the study is to characterize signaling cascades that regulate differentiation of adult intestinal stem cells or that initiate intestinal tumors and cancer. The intended methodology will utilize laboratory mouse as a main experimental model. In the course of the PhD studies the “state-of-the-art” techniques, such as gene knockout or knockin, transgenesis, high-throughput molecular biology methods, will be employed. Suggested reading: M. Krausova and V. Korinek: Wnt signaling in adult intestinal stem cells and cancer. Cellular Signalling, December 2, 2013 (OPEN ACCESS Article).
pii: S0898-6568(13)00363-X. doi: 10.1016/j.cellsig.2013.11.032. [Epub ahead of print]

Supervisor: Vladimír Kořínek (korinek@img.cas.cz)

We are interested in the genetic basis of mammalian eye development. Our focus is on the role of transcription factors and signalling cascades, especially on the role of Pax6 gene, Wnt/β-catenin signalling pathway and their genetic interaction. A combination of gain-of-function (transgenic) and loss-of-function (conditional knock-outs) approaches is used. Our second main interest is eye evolution. Early morphological studies have suggested that eye has evolved multiple times during the course of evolution. In contrast, more recent genetic data indicate a conserved role of Pax6 and some other transcription factors in eye formation in a wide range of animals. Several model systems including amphioxus, scallop, medaka and jellyfish are used in the laboratory to study various aspects of eye evolution.

Candidate’s profile (requirements):
M.Sc. or equivalent in molecular, cell or in developmental biology.

PhD project:
Successful applicants will study the role of selected transcription factors (such as Pax6) during mouse eye development. The following techniques will be applied: Cre/loxP conditional mutagenesis, phenotypic analysis, advanced imaging, cell sorting, in vitro differentiation of ES cells, ChIP-seq and RNA-seq.

Supervisor: Zbyněk Kozmik (kozmik@img.cas.cz)

PhD Project:
Successful applicants will study evolution of developmental control mechanisms (evo-devo). Gene-based comparative approach in multiple selected animal models will be used. The following techniques will be applied: gene isolation, bioinformatic analysis, gene expression analysis using whole-mount in situ hybridization and RNA-seq, gene perturbation using transgenesis and programmable nucleases (TALEN, CRISPR/Cas9).

Supervisor: Zbyněk Kozmik (kozmik@img.cas.cz)

Research topics: Functional gene mapping, leishmaniasis, atopy

The research programme of the laboratory aims to identify genes and molecular mechanisms involved in control of immune response and susceptibility to complex infectious diseases. We focus on complex diseases because they are responsible for the largest part of human morbidity and mortality and their genetic analysis is subject of an intensive international effort. They are controlled by multiple genes and hence their pathogenesis cannot be explained by effects of a single gene with omission of others. Leishmaniasis is such a complex disease and it has served as a major paradigm of immune response to an infectious agent.

Supervisor: Marie Lipoldová (marie.lipoldova@img.cas.cz)

Research topics: Cell cycle, checkpoint, protein phosphorylation, oncogenic transformation

In our recently established laboratory we employ cell biology, molecular biology and biochemical approaches to identify molecular mechanisms that control cellular responses to DNA damage. In particular we focus on protein phosphatase PPM1D/Wip1 that plays an essential role in switching off the DNA damage response pathway, termination of the checkpoint and control of checkpoint recovery. PPM1D/Wip1 is an important negative regulator of the tumor suppressor p53. Recent data from transgenic mice and from human tumors implicate PPM1D/Wip1 as oncogene. Our work aims to decipher molecular mechanisms regulating function of PPM1D/Wip1 in human cells and in mouse models. In addition, we use chemical genetics to evaluate PPM1D/Wip1 as a potential pharmacological target.

Candidate’s profile (requirements):
Eligible candidates should have M.Sc. degree or equivalent in cell/molecular biology or medicine and show a deep interest in experimental work.

PhD Project:
Title: Role of PPM1D/Wip1 mutations in cancer predisposition

Genome integrity of eukaryotic cells is protected by a DNA damage response pathway that coordinates the cell cycle progression with ongoing DNA repair. In our Cancer Cell Biology lab we use cell/molecular biology and biochemical techniques to study molecular mechanisms underlying these events. Recently we have identified novel clinically relevant mutations in the PPM1D gene that result in production of truncated form of Wip1 phosphatase and severely affect cellular responses to DNA damage. This PhD project will focus on functional characterization of these truncated Wip1 mutants. We will also use transgenic mouse models to investigate the oncogenic potential of truncated Wip1 in several cancer types.

Supervisor: Libor Macůrek (libor.macurek@img.cas.cz)

PhD Project:
Title: Role of R2TP complex in DNA damage response and cell cycle control

R2TP complex plays important role in transcription, chromatin remodelling and DNA damage response. We have recently described that an essential subunit of the R2TP complex protein PIH1D1 exhibits unique phospho-binding properties. This PhD project will focus on the molecular mechanisms underlying essential functions of the R2TP complex and functional characterization of recently identified interacting partners of PIH1D1. We will further investigate the mechanism of p53 stabilization by R2TP complex and its regulation in context of the cell cycle and DNA damage response. Suitable candidates should have M.Sc. degree or equivalent in cell/molecular biology or biochemistry.

Supervisor: Zuzana Hořejší (zuzana.horejsi@img.cas.cz)
Co-supervisor: Libor Macůrek (libor.macurek@img.cas.cz)

Research topics:  Proteases and their inhibitors, transgenesis, embryogenesis, aging and epigenetics, neural development

Our department has an exceptional role in IMG, serving as an incubator in which new research projects and groups as well as research infrastructure (partly core facilities) develop for the project of BIOCEV. Although thematically distinct, all groups and projects are based on the usage of mouse models as a tool to reveal gene functions in the complexity of the whole organism. Proteases in physiology and disease.

Candidate’s profile (requirements):
We are seeking outstanding self-motivated candidates with master’s degree in molecular biology, physiology, general biology, biochemistry or related fields. We are offering research at a state-of-the-art equipped institute with experienced colleagues, international working environment and international collaborations.

PhD project:
Title: Research project in E3 ubiquitin ligases.

Regulation of protein degradation via ubiquitination is an important mechanism which was not thoroughly studied. This system regulates a vast majority of signalling processes and is therefore very interesting as a potential source of new drug targets. PhD. candidate would investigate several proteins likely involved in cardiovascular and neural functions, while using state of the art techniques ranging from cloning, through protein work, transgenic animal utilization and in vivo experiments.

Supervisor: Radislav Sedláček (radislav.sedlacek@img.cas.cz)

PhD Project:
Title: Phenotypic analysis of mice deficient in Farp1

The first knock-out allele for Farp1 has recently been generated by our group. Major focus will be on liver (healthy vs. challenged models) and intestine. At molecular level, interactions with TGF pathway and cytoskeletal components determining induction of fibrotic changes and epithelial barrier function will be addressed.

Supervisor: Radislav Sedláček (radislav.sedlacek@img.cas.cz)

PhD Project:
Title: The impact of liver-specific deficiency of plectin on tensional homeostasis and pathology

We have recently shown that plectin controls keratin cytoarchitecture and cellular stress response. Based on our preliminary results we hypothesize that plectin confers features of keratin networks essential for their hepatoprotective function. Major focus will be on characterizing and comparing pathogenesis of acute, chronic and biliary fibrosis using our newly generated liver-specific plectin knock-out mouse model.

Supervisor: Radislav Sedláček (radislav.sedlacek@img.cas.cz)

Research topics: RNA splicing, spliceosome formation, alternative splicing, retinitis pigmentosa, nuclear structure

Our long-term interest is to determine how cells decode information stored in the genome. Information in human DNA is fragmented and we study processes and complexes that splice these fragments together. We focus on molecules called RNAs that serve as information couriers between DNA and proteins.

Candidate’s profile (requirements):
M.Sc. (Mgr.) degree or equivalent in biochemistry or molecular/cellular biology.

PhD project:
The PhD project will be focused on a role of long non-coding RNA in regulation of alternative pre-mRNA splicing. Research will include characterization and manipulation of long non-coding RNAs in human cell cultures.

Supervisor: David Staněk (stanek@img.cas.cz)