In our research group, we investigate the regulation of haematopoietic stem cell (HSC) maintenance and fate by transcription factors and their target genes, determine whether these elements are altered in human leukaemias (in particular acute myeloid leukaemia, AML), and elucidate their contribution to leukaemogenesis…
Supervisor
Meritxell Alberich Jordà
Project description
Haematopoietic stem and progenitor cells (HSPCs) constitute an essential population of cells which reside in the bone marrow. They orchestrate the continuous generation of mature blood cells throughout an individual’s lifespan, and thus the preservation and maintenance of their function is critical for the process of haematopoiesis. Disruptions in the HSPC pool have been associated with the onset of leukemia, underscoring the significance of understanding and safeguarding their integrity.
Our recent publications shed light on the effects that inflammation exerts on HSPCs, leading to changes in their characteristics and function. In this project, we will explore the regulatory mechanism that protect and maintain HSPCs, determine how they are altered under inflammatory conditions, and investigate how to develop strategies to reverse the detrimental effects observed. To achieve these goals, we will employ a multifaceted approach, combining in vitro cell cultures, murine models, and -omics screenings.
In essence, this research stands as a pivotal exploration into the dynamic interplay between inflammation and HSPC regulation, with the ultimate aim of contributing to the development of targeted therapeutic strategies for preserving haematopoietic homeostasis and preventing the onset of debilitating conditions such as leukemia.
Candidate profile
The laboratory of haematooncology is searching for a highly motivated, enthusiastic and hard-working Ph.D. student. The candidate should hold a master degree in genetics, molecular biology, cell biology, or in a related field. Previous animal work and bioinformatic skills will be positively evaluated. The candidate should be willing to work with murine models. Excellent English is required. The candidate should be a team-player and willing to work with other lab members and international collaborators.
We offer a friendly, international, and supporting environment in a state-of-the-art institution.
Suggested reading
The main function of the ubiquitin-proteasome system (UPS) is to degrade unneeded or damaged proteins. Cullin-RING ubiquitin ligases (CRLs) mediate ubiquitination of numerous substrates. Our main research focus is to reveal novel substrates of CRLs involved in cancer progression, stress response or cell cycle…
Supervisor
Lukáš Čermák
Project description
This project aims to investigate the pivotal role of the proteasome in the regulation of apoptosis within cancer cells. The proteasome, a cellular complex responsible for protein degradation, is known to play a crucial role in maintaining cellular homeostasis. However, its specific involvement in modulating apoptosis in cancer cells remains understudied. Through a series of experiments utilizing cancer cell lines and proteasome inhibitors, we intend to unravel the intricate mechanisms by which the proteasome influences apoptotic pathways. By identifying key protein targets and understanding the interplay between the proteasome and apoptosis regulators, we hope to shed light on potential therapeutic strategies for manipulating apoptosis in cancer cells. This research not only contributes to our fundamental understanding of cell biology but also holds promise for the development of targeted therapies that exploit the proteasome’s control over apoptosis in the context of cancer treatment.
Candidate profile
We invite enthusiastic and goal-oriented students with a keen interest in molecular biology and basic understanding of biochemical methods to join this research project. A comprehensive understanding of fundamental molecular biology techniques will be highly beneficial in unraveling the intricacies of proteasome-mediated control of apoptosis in cancer cells.
Suggested reading
Our laboratory is focused on understanding the molecular mechanisms governing signal transduction from the plasma membrane receptors to the cytoplasm…
Supervisor
Petr Dráber
Project description
Mast cells are immune cells with multifaceted functions in homeostasis and diseases. They have traditionally been associated with type I allergies, such as rhinitis, asthma, and urticaria, causing a global health burden of approximately 20% of the human population worldwide. They play essential roles in both innate and adaptive immunity. Accumulating evidence suggests that a complex network of inhibitory and activating receptors controls mast cell responsiveness to various stimuli. Recently, we found that mast cells from mice with defects in the ORMDL family proteins, inhibitors of serine palmitoyltransferase, exhibit increased antigen-induced degranulation and cytokine response. Mass spectrometry analysis revealed that ORMDL-deficient cells express increased leukocyte-associated immunoglobulin-like receptor 1 (Lair-1). This was an unexpected finding, given that LAIR-1 is a negative regulator of immunoreceptor signaling in several immune cell types. In this project, we will test the hypothesis that increased expressions of LAIR-1 counterbalance the enhanced response of mast cells from ORMDL-deficient mice. We will also test the hypothesis using human mast cell lines ROSA that LAIR-1 regulates the progress of mastocytosis. In the frame of the project, we will also prepare and test bispecific constructs, aggregating LAIR-1 with IgE receptor or cKIT, for the treatment of mast cell-mediated allergies and other inflammatory diseases and mastocytosis. Various techniques will be used to address the research questions of the project, including cell culture of different cell types, analysis of mast cell activation by antigen, immunoprecipitation of selected molecules followed by mass spectrometry, gene expression studies by whole genome transcriptome analysis, immunoblotting and other immunochemical procedure. Part of the project will also be the production of bispecific recombinant constructs for enhanced crosstalk of LAIR-1 with the high-affinity IgE receptor or c-kit and testing the constructs under in vitro and in vivo conditions. In vivo experiments will require working with laboratory mice.
Candidate profile
Techniques of molecular immunology
Suggested reading
Genomics, bioinformatics, next-generation sequencing, cancer transcriptomics: Activity of our laboratory is based on advanced applications of genomics, transcriptomics and bioinformatics, the most vigorously developing disciplines of contemporary life sciences…
Supervisor
Edvard Ehler
Project description
The development of ancient DNA (aDNA) technologies in recent years gave rise of vast number of human genomic samples, especially from the prehistorical Europe. Most of the known samples are coming from the first four millennia before CE, a periods described as Neolithic, Bronze Age and Iron Age epochs based on associated archaeological findings. These populations are described primarily using their cultural features (archaeological findings, e.g., pottery, burials, food production, technology). The biological relationship between different populations living at that time are only beginning to be unfolded. The applicant will assist in bioinformatic processing of aDNA genomic samples (within an awarded CZ-PL Weave international grant project), focusing on populations from Bronze and Iron Age period from central Europe. The obtained genomic data will be utilized in the main goal of the proposed PhD project – to test different methods of detection of the population substructure and similarities, and identification of population admixture or isolation events. The applicant will be encouraged to test various population genetics methods, as well as modern dimensionality reduction and machine-learning techniques and approaches to describe and comprehend the genomic data on population level. This should allow us to better recognize the genetic background of the target populations, estimate the gene flow between them and thus the regional variability, and help us ascertain their social structure, marriage patterns and identify possible migrations.
Candidate profile
We are looking for a highly motivated PhD student with interest in population genomics, aDNA studies and archaeogenetics. The candidate should hold a master degree in bioinformatics, computational biology or a related field. She/he should be able to program in Python, experience in data-mining and/or machine-learning projects is a plus.
Suggested reading
We investigate embryonic development using an integrative approach combining molecular biology, cell biology, developmental biology, genetics, biochemistry, and bioinformatics in order to get insight into the molecular mechanisms underlying the process of animal development and its tinkering during the course of evolution…
Supervisor
Zbyněk Kozmik
Project description
Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. The genome of invertebrate chordate amphioxus has not undergone whole-genome duplication and serves as a proxy to ancestral chordates. Although amphioxus lacks the specializations and innovations of vertebrates, it shares with them a basic body plan and has multiple organs and structures homologous to those of vertebrates. For these reasons, amphioxus has widely been used as a reference outgroup to infer ancestral versus novel features during vertebrate evolution. Over the past few years amphioxus has become an established laboratory model and its cultures can be maintained throughout the year at the Institute of Molecular Genetics. This allows for an implementation of plethora of molecular and genetics approaches common to classical vertebrate models such as mouse, chick or fish. Moreover, recent publication on Amphioxus functional genomics and the origins of vertebrate gene regulation (Marletaz et al., Nature 564(7734):64-70) provides a huge genomic resource for future studies focused on gene regulatory mechanisms underlying evolution of vertebrate body plan.
Project will focus on evolution of cell types, ancestral chordate features and vertebrate-specific innovations, using comparative analysis between amphioxus and vertebrates. The methods used will include basic bioinformatics, gene expression studies (single cell RNA-seq, whole-mount in situ hybridization, and immunohistochemistry), analysis of gene knockouts established in the lab using CRISPR/Cas9 system, and reporter gene transgenesis.
Candidate profile
We are searching for a highly motivated and hard-working PhD student with a strong interest in animal evolution and evolution of development (evo-devo). The candidate should hold a master degree in zoology, genetics, molecular biology, cell biology, or in a related field.
Suggested reading
Our long-term goal is to determine how the spliceosome assembles at the right time and place inside the cell. We are investigating how nuclear architecture contributes to the correct spliceosome formation, and studying the molecular principles of the control mechanism that distinguishes correctly assembled spliceosome particles from the defective ones…
Supervisor
David Staněk
Project description
Mutations in several RNA splicing factors affect specific cells in the retina and lead to hereditary retinal degeneration – retinitis pigmentosa (RP). In addition, numerous mutations in retina-specific genes that also cause RP are found in introns and have potential negative effects on the splicing of these genes (e.g. RHO). Thus, splicing defects are key factors in the development of RP. Despite intensive research, the molecular mechanisms of cell-specific susceptibility to these mutations remain unclear. In this project, we plan to use relevant biomodels to study defects caused by RP mutations in splicing factors in target cell types. The candidate will analyze the effect of RP mutations in different genes on in vitro generated human retinal organoids and retinal pigment epithelium. We will examine defects in RNA splicing and tissue-specific RNA production and identify genes with aberrant splicing that we will subsequently correct. She/he will also test the hypothesis that cellular sensitivity to RP mutations correlates with reduced expression of splicing factors. The results will allow us to identify potential treatments for RP. This project is part of Marie Skłodowska-Curie Training Doctoral Network focused on retinal dystrophies (ProgRET), which includes eight European academic teams and four industrial partners, which are leaders in retinal dystrophy research.
Candidate profile
Eligibility – M.Sc. or equivalent education in molecular biology, developmental biology or biochemistry obtained outside the Czech Republic.
Suggested reading
In our laboratory we study processes and mechanisms, which govern epithelial morphogenesis and homeostasis, and how their deregulation can lead to developmental defects and cancer…
Supervisor
Zuzana Sumbalová Koledová
Project description
Epithelial-stromal interactions play a crucial role in mammary gland development and homeostasis. Stromal cells, such as fibroblasts, provide instructions for epithelial morphogenesis through paracrine signaling and extracellular matrix production and remodeling. In mammary epithelial organoid-fibroblast cocultures, we have recently described a new mechanism of fibroblast-induced epithelial morphogenesis mediated by fibroblast mechanical forces. In this project, the PhD candidate will investigate 1) the importance of fibroblasts mechanical forces in mammary epithelial morphogenesis in vivo using genetic mouse models, and 2) regulation of fibroblast mechanical activity using scRNA sequencing analysis and functional in vitro and in vivo experiments.
Candidate profile
Suggested reading
The group studies evolution of genes and their regulations, particularly post-transcriptional regulations and genes that mediate it, mainly in the context of the female germline in mice…
Supervisor
Petr Svoboda
Project description
The lab currently studies evolution of mammalian RNA silencing pathways and focuses on several specific aspects of RNAi and piRNA pathways. A PhD candidate will have an opportunity to choose as a main project either evolution of small RNA biogenesis and effector complex formation or adaptations and functional divergence of the piRNA pathway. The laboratory uses rodents and slugs as main experimental models. Laboratory work will range from biochemistry of ribonucleoprotein complexes to genetic modifications and phenotype analysis (largely involving long and small RNA analyses by RNA sequencing).
Candidate profile
We are looking for a curious and motivated PhD student with some experience with molecular biology, experience with laboratory animals, mammalian cell culture, molecular cloning, protein biochemistry or bioinformatics will be an advantage.
Suggested reading
In the Laboratory of Cell Motility, we study the eukaryotic flagellum and cilium (the terms are interchangeable), a fascinating organelle with motile, signalling and sensory roles…
Supervisor
Vladimír Varga
Project description
Primary cilia have signalling and sensory functions and serve as antennas in many human cell types. Their malfunctioning causes severe diseases called ciliopathies. The project will focus on understanding of the recently described arrangement of microtubules forming the primary cilium axoneme. These terminate at various distances from the ciliary base with only several extending to the very tip of the cilium, which is very different to the canonical axoneme of motile cilia. The project will combine advanced imaging approaches, such as high resolution live cell imaging, expansion microscopy, correlative light and electron microscopy, with micromanipulations and molecular biology techniques to study how is the microtubule arrangement established, how dynamic it is, what are its implications for ciliary processes, and whether its alteration leads to ciliary malfunctioning. The project is supported by a collaborative Czech-USA grant.
Candidate profile
The candidate should have an interest in cell biology, in particular biology of the eukaryotic cytoskeleton. An experience in light or electron microscopy imaging and cell culturing would be beneficial. A good command of English is expected given the international nature of the project.
Suggested reading