PhD Program

Research labs with open PhD positions

Show all Project Summaries

 

Petr Bartůněk – Cell Differentiation
www.img.cas.cz/research/petr-bartunek
Project: How epigenetic modulators influence phenotypic bi-stability.

Project Summary

Project Title: How epigenetic modulators influence phenotypic bi-stability.
Supervisor: Kallayanee Chawengsaksophak

Project Description:
A dominant ENU mutagenesis screen in mice, conducted in the laboratory of Prof. Emma Whitelaw (Australia) has been quite successful in identifying genes which modify epigenetic state. Preliminary analysis of one of the earliest identified mutants, MommeD3, uncovered very unusual and unique phenotypic features in homozygous embryos, including biphenism, imprinting defects, neural degeneration and profound anemia. At that time, the underlying genetic point mutation could not be identified. More recently, taking advantage of next generation sequencing approaches, we have been able to revisit this project and successfully identify the causative mutation. Combining formal description of the embryonic MommeD3 phenotype with global analyses of RNA expression and DNA methylation, the overall aim of the project will be to link the observed stochastic bi-stable embryonic phenotype with potential alterations in genomic imprinting networks.

Candidate Profile:
The applicant must hold, or be about to complete, a Master’s degree in molecular biology, genetics or related field of life sciences. The candidate should possess proficiency in written and spoken English and be comfortable with small animal handling and dissection. The candidate will develop skills in classical embryology and transcriptomics (RNAseq, bisulfite sequencing, etc.)

Suggested reading:

  • Daxinger L, et al. An ENU mutagenesis screen identifies novel and known genes involved in epigenetic processes in the mouse. Genome Biol. 2013;14(9):R96.
  • Dalgaard K, et al. Trim28 Haploinsufficiency Triggers Bi-stable Epigenetic Obesity. Cell. 2016 Jan 28;164(3):353-64.

 

Tomáš Brdička – Leukocyte Signalling
www.img.cas.cz/research/tomas-brdicka
Project: Adaptor protein WBP1L in hematopoiesis, immune response and leukemia

Project Summary

Project Title: Adaptor protein WBP1L in hematopoiesis, immune response and leukemia
Supervisor: Tomáš Brdička

Project Description:
For a long time WBP1L has only been known at mRNA level as childhood leukemia marker, expression of which correlated with ETV6-RUNX1 translocation and favorable treatment outcome. Our recent work shows that WBP1L is an inhibitory adaptor protein, which is involved in the control of hematopoiesis and efficiency of bone marrow transplantation and mobilization. Using WBP1L deficient mice and cell lines, the candidate will study the mechanisms of how WBP1L regulates these processes. In addition, he/she will explore the role of WBP1L in immune responses and in leukemic cell biology. He/she will also contribute to the analysis of signaling pathways regulated by WBP1L. Finally, the candidate will collaborate with other lab members exploring the function of another inhibitory adaptor protein PSTPIP2. Here our effort will focus on explaining the mechanisms, by which PSTPIP2 regulates inflammatory immune response and how its absence contributes to the development of autoinflammatory disease.

Candidate Profile:
The candidate must hold a Master degree (or be close to its completion) in immunology, molecular/cell biology, biochemistry or in related field of life sciences. The applicant must have a strong interest in immunology and related biomedical sciences. Ability to communicate in English is required.

Suggested reading:

  • Borna, S. et al. (2020) Transmembrane adaptor protein WBP1L regulates CXCR4 signalling and murine haematopoiesis. J Cell Mol Med 24, 1980-1992
  • Kralova, J. et al. (2020) Dysregulated NADPH Oxidase Promotes Bone Damage in Murine Model of Autoinflammatory Osteomyelitis. J Immunol 204, 1607-1620
  • Borowicz, P. et al. (2020) Adaptor proteins: Flexible and dynamic modulators of immune cell signalling. Scand J Immunol 92, e12951

 

Lukáš Čermák – Cancer Biology
www.img.cas.cz/research/lukas-cermak
Project: Regulated protein degradation in cancer development and therapy.

Project Summary

Project Title: Regulated protein degradation in cancer development and therapy.
Supervisor: Lukáš Čermák

Project Description:
The aim of the study is to characterize novel substrates of Cullin-dependent ubiquitin ligases and the significance of their degradation in the context of cancer biology and physiology. The intended methodology will include classical biochemical and molecular biology approaches in combination with proteome and genome scale studies, using modern mass-spectrometry analysis and screening methods utilizing CRISPR-mediated genome editing. The project will be supported by funding from the Grant Agency of the Czech Republic.

Candidate Profile:
M.Sc. or equivalent in molecular, cell and developmental biology or biochemistry; fluent in English

Suggested reading:

  • Cermak L, Pagano et al.: FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature. 2012
  • Skaar JR, Pagan JK, Pagano M.: Mechanisms and function of substrate recruitment by F-box proteins. Nature Rev Mol Cell Biol. 2013

 

Martin Gregor – Integrative Biology
www.img.cas.cz/research/martin-gregor
Project: The role of extracellular matrix stiffness and composition in development of lung fibrosis

Projects Summary

Project Title: The role of extracellular matrix stiffness and composition in development of lung fibrosis
Supervisors: Martin Gregor

Project Description:
Lung fibrosis is excessive scarring process resulting from chronic insults of heterogenous etiology. The major hallmark of lung fibrosis is deposition of fibrous extracellular matrix (ECM) synthetized mainly by lung myofibroblasts. The major goal of this project is analysis of interplay between myofibroblasts and altering ECM niche, using newly developed mouse model harboring myoblasts with compromized ECM-receptor signaling. This phenomena will be then studied in vitro, using human myofibroblast line and mouse primary myofibroblasts to better understand the processes regulating deposition and composition of ECM in llung fibrosis.

The successful candidates will learn and utilize advanced cell-biology, molecular-biology, physiology, imaging techniques and atomic force microscopy, while developing and analyzing various mouse models.

Candidate Profile:
We are seeking outstanding self-motivated candidates with master’s degree in molecular biology, physiology, 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.

Suggested reading:

  • Gregor M. et al. Mechanosensing through focal adhesion-anchored intermediate filaments. FASEB J., 28:715-29, 2014.
  • Schiller H.B. et al. Time- and compartment-resolved proteome profiling of the extracellular niche in lung injury and repair. Mol Syst Biol., 11:819, 2015.
  • Jones M.G. et al. Nanoscale dysregulation of collagen structure-function disrupts mechano-homeostasis and mediates pulmonary fibrosis. Elife, 7:e36354, 2018.
  • Duscher D. Mechanotransduction and fibrosis. J Biomech. 47:1997–2005, 2014.

 

Zdeněk Hodný – Genome Integrity
www.img.cas.cz/research/zdenek-hodny
Project: Complex DNA damage, ribosomal DNA, genome stability and cancerogenesis

Project Summary

Project Title: Complex DNA damage, ribosomal DNA, genome stability and cancerogenesis
Supervisor: Pavla Vašicová

Project Description:
Complex irreparable DNA damage emerges as a pathogenic factor contributing to human age-associated diseases including cancer. The nature of these lesions and linked molecular mechanisms are currently in the center of intensive investigation. One of the proteins that is involved in DNA damage response and maintenance of genome stability is promyelocytic leukemia protein (PML). Our recent work shows that irreparable damage of ribosomal DNA leads to specific PML-mediated compartmentalization. The general aim of the proposed PhD project is to reveal the role of PML in rDNA maintenance and to describe the processes that take place in this PML-specific compartment. Employing biotin proximity labeling and mass-spectrometry analysis, a set of potential PML interactors has been already obtained. The verification of the interactors by alternative approaches and highlighting their specific functional role in maintenance of rDNA will be the specific aims of the project.

Candidate Profile:
The candidates should be graduates in molecular/cell biology, genetics, biochemistry, or related life sciences, fluent in English. We are seeking for self-motivated candidate with passion for scientific work.

Suggested reading:

  • Imrichova, T., et al. (2019). „Dynamic PML protein nucleolar associations with persistent DNA damage lesions in response to nucleolar stress and senescence-inducing stimuli.“ Aging 11(17): 7206-7235.

 

Libor Macůrek – Cancer Cell Biology
www.img.cas.cz/research/libor-macurek
Project: Screening for proteins involved in G-quadruplex and R-loop metabolism

Project Summary

Project Title: Screening for proteins involved in G-quadruplex and R-loop metabolism
Supervisors: Jana Dobrovolná, Pavel Janščák

Project Description:
DNA replication is an essential and one of the most complex processes in the cell. Not only exogenous DNA damage but also intrinsic DNA structures including G-quadruplexes (G4) and R-loops, their stabilization or unscheduled formation represent major replication obstacles with possible detrimental effects on genome integrity. Not surprisingly, those processes are pharmacologically targeted in anticancer therapy, despite the fact that only little is known about the underlying molecular mechanisms. It becomes apparent that maintenance of processive DNA replication requires sophisticated protein networks beyond the core replisome. Whether there is a direct crosstalk between G4 and R-loops, what proteins are involved in their homeostasis and what are the factors diversifying between their beneficial and pathological roles is not well understood. The goals of our research are to identify proteins associated with G4 and R-loop structures and understand their roles in G4/R-loop formation and resolution as well as relationship to replication fork progression and associated repair. We will apply mass spectrometry-based proteomics approaches, including APEX-based proximity labeling and chromatin affinity precipitation methods, coupled with functional siRNA screens to identify new factors involved in metabolism of R-loops and G4s in conjunction with ongoing replication.

Candidate Profile:
Applicants should be graduates in Molecular Biology/Cellular Biology/Biochemistry with a strong interest in basic research and experimental work. Good English and independent thinking is required. The projects offer training in a broad range of molecular, cell biological and biochemical techniques. The student will also undergo short-term trainings at the Institute of Molecular Cancer Research of the University of Zurich where he/she will be exposed to front-line research in the field of DNA repair and cancer.

Suggested reading:

  • Bauer M, Nascakova Z, Mihai AI, Cheng PF, Levesque MP, Lampart S, Hurwitz R, Pfannkuch L, Dobrovolna J, Jacobs M, Bartfeld S, Dohlman A, Shen X, Gall AA, Salama NR, Töpfer A, Weber A, Meyer TF, Janscak P, Müller A. The ALPK1/TIFA/NF-κB axis links a bacterial carcinogen to R-loop-induced replication stress. Nat Commun. 2020 Oct 9;11(1):5117
  • Chappidi N, Nascakova Z, Boleslavska B, Zellweger R, Isik E, Andrs M, Menon S, Dobrovolna J, Balbo Pogliano C, Matos J, Porro A, Lopes M, Janscak P.: Fork Cleavage-Religation Cycle and Active Transcription Mediate Replication Restart after Fork Stalling at Co-transcriptional R-Loops. Mol Cell 2020, 77(3):528-54

 

Ondřej Štěpánek – Adaptive Immunity
www.img.cas.cz/research/ondrej-stepanek
Project: T-cell signaling in models of human diseases

Project Summary

Project Title: T-cell signaling in models of human diseases
Supervisors: Ondřej Štěpánek

Project Description:
T cells represent the adaptive arm of immunity against infections and cancers. However, T cells also induce autoimmune diseases when they lose self-tolerance. The key to the biology of T-cells is their unique antigen receptor, which discriminates self and non-self antigens. Moreover, additional receptors and signaling pathways modulate T-cell fate decisions. The student will discover novel mechanisms in key T-cell signaling pathways and investigate their importance in established animal models of infection, cancer, and autoimmunity.
The Lab of Adaptive Immunity offers a productive and stimulating environment (see our recent publications). We have established multiple national and international collaborations and we are well supported by domestic and international research grants. Our lab is the first and only immunological research group with an ERC grant in the country.

Candidate Profile:
We are looking for highly motivated and smart candidates with a master degree in immunology, cell biology, molecular biology, biochemistry, medicine or a related field. The candidate must be able to communicate in English. Additional skills and experience (wet lab, coding, languages etc.) are appreciated but not essential. If you want to make a huge step towards your successful career in life sciences, get great theoretical and practical skills, and finish your PhD with a decent research paper in a timely manner, do not hesitate to apply! The student will receive 24,000 CZK salary plus a non-taxable stipend of 10,500 CZK per month. The candidates are strongly encouraged to contact the PI, Ondrej Stepanek, directly.

Suggested reading:

  • Dynamics of the Coreceptor-LCK Interactions during T Cell Development Shape the Self-Reactivity of Peripheral CD4 and CD8 T Cells. Horkova V, Drobek A, Mueller D, Gubser C, Niederlova V, Wyss L, King CG, Zehn D, Stepanek O. Cell Rep. 2020 Feb 4;30(5):1504-1514.e7.
  • Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells. Drobek A, Moudra A, Mueller D, Huranova M, Horkova V, Pribikova M, Ivanek R, Oberle S, Zehn D, McCoy KD, Draber P, Stepanek O. EMBO J. 2018 Jul 13;37(14):e98518. doi: 10.15252/embj.201798518.
  • Coreceptor scanning by the T cell receptor provides a mechanism for T cell tolerance. Stepanek O, Prabhakar AS, Osswald C, King CG, Bulek A, Naeher D, Beaufils-Hugot M, Abanto ML, Galati V, Hausmann B, Lang R, Cole DK, Huseby ES, Sewell AK, Chakraborty AK, Palmer E. Cell. 2014 Oct 9;159(2):333-45. doi: 10.1016/j.cell.2014.08.042.

Poslední změna: 17. prosinec 2020