PhD Programme

 

Open PhD positions for the 2019/2020 academic year will be available soon.

Research labs with open PhD positions

Show all Project Summaries

Meritxell Alberich Jordà – Haematooncology
www.img.cas.cz/research/meritxell-alberich-jorda
Project: Genetic and epigenetic changes in hematopoietic stem cells during chronic inflammation

Project Summary

Project Title: Genetic and epigenetic changes in hematopoietic stem cells during chronic inflammation
Supervisor: Meritxell Alberich Jordà

Project Description:
This project will determine the molecular changes in enhancers and promoters that chronic inflammation induces in hematopoietic stem cells. Next, we will investigate how these changes contribute to the development of leukemia, an hematological disorder characterized by the accumulation of malignant cells in bone marrow and blood. Together, the results of this project will uncover the mechanisms regulating hematopoietic stem cell maintenance and fate in the context of chronic inflammation, and lay the path to identify new therapeutic strategies in leukemia.

Candidate Profile:
The laboratory of hemato-oncology 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. 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 and supporting environment in a state-of-the-art institution.

Suggested reading:

  • Liss A, Ooi CH, et al. The gene signature in CCAAT-enhancer-binding protein α dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors. Haematologica. 2014 Apr;99(4):697-705.
  • Zjablovskaja P, Kardosova M, et al. EVI2B is a C/EBPa target gene required for granulocytic differentiation and functionality of hematopoietic progenitors. Cell Death Differ. 2017 Apr;24(4):705-716.
  • Wurm AA, Zjablovskaja P, et al. Disruption of the C/EBPα-miR-182 balance impairs granulocytic differentiation. Nat Commun. 2017 Jun 29;8(1):46.
  • Kardosova M, Zjablovskaja P, et al. C/EBPg is dispensable for steady-state and emergency granulopoiesis. Haematologica. 2018 Aug;103(8):e331-e335.

 

Keith Caldecott – Genome Dynamics
www.img.cas.cz/research/keith-caldecott
Project: Defective DNA Damage Responses in Neurodegeneration

Project Summary

Project Title: Defective DNA Damage Responses in Neurodegeneration
Supervisor: Hana Hanzlíková

Project Description:
DNA single-strand breaks (SSBs) are the most frequent DNA lesions arising in cells and are a major threat to cell survival and genetic integrity, as indicated by the elevated genetic deletion, embryonic lethality, and neurological disease observed if single-strand break repair (SSBR) is attenuated. Mice harbouring a brain-specific deletion of the critical SSBR protein XRCC1 recapitulate most of the phenotypes observed in patients with SSBR defects including cerebellar atrophy, ataxia and seizures. In this project we will focus on the generation and characterisation of new SSBR-defective mouse models, including a patient XRCC1 knock-in mutation. We will employ these model to address how unrepaired SSBs trigger neurodegeneration, highlighting new potential therapeutic approaches that might alleviate or prevent hereditary and/or sporadic neurodegenerative disease.

Candidate Profile:
The Institute of Molecular Genetics is an internationally renowned research institute that provides a stimulating and supportive environment spanning a range of experimental model systems and is located in a cutting edge research facility with state-of-art infrastructure and equipment. The project will also provide opportunity for periods of research in the Caldecott laboratory at the Genome Damage and Stability Center in Brighton, UK.

The successful applicant will be highly motivated and will have experience of working within a multidisciplinary team. Applicants must have a relevant master degree and preferably expertise in DNA damage responses and/or mice handling or at least must be enthusiastic and willing to work with murine model.

Suggested reading:

  • Hoch N & Hanzlikova H et al. XRCC1 Mutation is Associated with PARP1 Hyperactivation and Cerebellar Ataxia. Nature. 2017. 541:87-91.
  • Hanzlikova H et al. The Importance of Poly(ADP-Ribose) Polymerase as a Sensor of Unligated Okazaki Fragments during DNA Replication. Mol Cell. 2018. 71(2): 319-331.e3
  • Kalasova I & Hanzlikova H et al. Novel PNKP mutations causing defective DNA strand break repair and PARP1 hyperactivity in MCSZ. Neurol Genet. 2019. 5(2): e320.
  • Komulainen E et al. Poly(ADP-ribose) Polymerase-1 Hyperactivity at DNA Single-Strand Breaks Triggers Seizures and Shortened Lifespan. BioRxiv preprint. 2018. doi: http://dx.doi.org/10.110

 

Jiří Forejt – Mouse Molecular Genetics
www.img.cas.cz/research/jiri-forejt
Project: The role of PRDM9-mediated synapsis of meiotic chromosomes in hybrid sterility

Project Summary

Project Title: The role of PRDM9-mediated synapsis of meiotic chromosomes in hybrid sterility
Supervisors: Jiří Forejt

Project Description:
By using laboratory strains of mice as a model we identified Prdm9 as the first hybrid sterility gene in vertebrates. Although this model of hybrid sterility has proved robust and reproducible, its molecular mechanism remains largely unknown. Thus, in this project we will ascertain the role of Prdm9 in meiotic recombination and chromosome pairing in sterile mouse hybrids.

Candidate Profile:
The laboratory of Mouse Molecular Genetics is opening the position for a highly motivated Ph.D student. The candidate should hold a master degree in genetics or molecular biology. The bioinformatics skills and previous research experience in cell biology and biochemistry of meiosis is welcome but not necessary. Excellent English is required. We provide a friendly and supportive environment for continuous scientific growth.

Suggested reading:

  • Davies, B., E. Hatton, N. Altemose, J. G. Hussin, F. Pratto et al., 2016 Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice. Nature 530: 171–176.
  • Forejt J. Genetics: Asymmetric breaks in DNA cause sterility. Nature 530:167-8.2016.
  • Gregorova, S., Gergelits, V. Chvatalova, I., Bhattacharyya, T., Valiskova B., Fotopulosova V., Jansa, P., Wiatrowska, D., Forejt, J, 2018 Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice. Elife pii: e34282

 

Martin Gregor – Integrative Biology
www.img.cas.cz/research/martin-gregor
Project: The role of extracellular matrix stiffness and composition in development of liver
Project: The role of plectin in cholestasis-induced adaptive response in liver

Projects Summary

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

Project Description:
Liver fibrosis is excessive scarring process resulting from chronic insults of heterogenous etiology. The major hallmark of liver fibrosis is deposition of fibrous extracellular matrix (ECM) synthetized mainly by hepatic stellate cells (HSCs). The major goal of this project is analysis of interplay between HSCs and altering ECM niche, using newly developed mouse model harboring HSCs with compromized ECM-receptor signaling. This phenomena will be then studied in vitro, using human HSC line and mouse primary HSCs to better understand the processes regulating deposition and composition of ECM in liver 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.
  • Burgstaller G. et al. Keeping the vimentin network under control: cell–matrix adhesion-associated plectin 1f affects cell shape and polarity of fibroblasts. Mol. Biol. Cell, 21:3362–3375, 2010.
  • Jirouskova M. et al. Plectin Controls Biliary Tree Architecture and Stability in Cholestasis. J Hepatol., 68:1006-1017, 2018.
  • Duscher D. Mechanotransduction and fibrosis. J Biomech. 47:1997–2005, 2014.

Project Title: The role of plectin in cholestasis-induced adaptive response in liver
Supervisors: Martin Gregor

Project Description:
Cholestatic liver diseases are highly prevalent causes of progressive liver disease with a significant morbidity and mortality. A prominent group of genes that becomes upregulated in
response to a cholestatic insult encodes keratins and plakin cytolinkers. Using liver-specific knock-out mice we have recently shown that deficiency for plectin, a highly versatile cytolinker,
has detrimental effect in cholestatic liver injury.

To elucidate the mechanisms by which plectin governs cholestasis-induced adaptive response we will analyze the role of plectin in:

  1. adaptation of hepatobiliary transport systems,
  2. activation and expansion of hepatic progenitor cells, and
  3. hepatocyte-driven liver regeneration.

To fulfill these aims we will combine analysis of liver injury mouse models with analyses of primary and CRISPR/Cas9-targeted cells grown in 2D and 3D cultures.

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:

  • Jirouskova M. et al. Plectin Controls Biliary Tree Architecture and Stability in Cholestasis. J Hepatol., 68:1006-1017, 2018.

 

Zdeněk Hodný – Genome Integrity
www.img.cas.cz/research/zdenek-hodny
Project: Unraveling the molecular mechanism of dual response of cancer cells to IFNγ/TGFβ
Project: Role of cell-to-cell communication in malignant traits of glioblastoma multiforme

Projects Summary

Project Title: Unraveling the molecular mechanism of dual response of cancer cells to IFNγ/TGFβ
Supervisor: Iva Kubíková

Project Description:
New experimental data suggests that many cytotoxic cancer therapies can enhance epithelial-mesenchymal transition, induce stem-like characteristics and increase migratory and invasive properties of malignant cells leading to the metastatic behavior. More than 90% of cancer-related mortality is caused by metastatic disease. TGFβ and IFNγ are cytokines well known for their dual role on cancer cells. They have primarily cytostatic effects or can promote cell senescence. However, cancer cells are frequently characterized by the switch to a growth-promoting response to TGFβ and IFNγ which supports phenotypic transitions of cancer cells essential for metastatic process. In the present project we aim to unravel the molecular mechanism behind the two modes of cancer cell response to TGFβ/IFNγ. We will focus on glioblastoma using 3D cell culture and brain organoid in vitro models.

Candidate Profile:
The laboratory of Genome Integrity is looking for a PhD student with background in molecular biology, biochemistry, physiology or medicine. The candidate should be proficient in English.

Suggested reading:

  • Hubackova S, Kucerova A, et al. IFNγ induces oxidative stress, DNA damage and tumor cell senescence via TGFβ/SMAD signaling-dependent induction of Nox4 and suppression of ANT2. Oncogene. 2015 May: 1–14.
  • Gorgoulis V, Adams PD, et al. Cellular Senescence: Defining a Path Forward. Cell. 2019 Oct; 179 (4): 813-827.
  • Azari H, Millette S, et al. Isolation and Expansion of Human Glioblastoma Multiforme Tumo rCells Using the Neurosphere Assay. Journal of Visualized Experiments. 2011 Oct; 56 (e

Project Title: Role of cell-to-cell communication in malignant traits of glioblastoma multiforme
Supervisor: Zdeněk Hodný

Project Description:
Astrocytoma grade IV (glioblastoma multiforme; GBM) belongs to most deadliest malignant tumors in humans. The current therapeutic modality of GBM represents surgery combined with fractionated brain irradiation and treatment with alkylating agents, however the outcome of therapy is dissatisfactory. The main goal of the project will be to understand glioblastoma biology utilizing an in vitro model of human brain organoids. We will focus on the identification of signalling molecules mediating communication of glioma cells with cerebral organoid tissue to unravel factors supporting proliferation, invasiveness and therapeutic resistance of malignant cells with perspective to improve current or design novel therapeutic approaches to manage GBM. The project will involve culturing organoids, advanced fluorescence microscopic techniques, transcription profiling, mass spectrometry and molecular biology approaches such as manipulation of gene expression.

Candidate Profile:
We are searching for highly motivated Ph.D. student with enthusiasm and passion for research work. The candidate should hold a master degree in life sciences (biology, genetics, biochemistry), medicine or related field.

Suggested reading:

  • Lancaster, M.A., and J.A. Knoblich. 2014. Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc. 9:2329-2340.
  • Lancaster, M.A., et al. 2013. Cerebral organoids model human brain development and microcephaly. Nature. 501:373-379.
  • Linkous, A., et al. 2019. Modeling Patient-Derived Glioblastoma with Cerebral Organoids. Cell reports. 26:3203-3211.e3205.
  • Oliveira, B., A. et al. 2019. Modeling cell-cell interactions in the brain using cerebral organoids. Brain Res. 1724:146458.

 

Pavel Hozák – Biology of the Cell Nucleus
www.img.cas.cz/research/pavel-hozak
Project: The role of phosphoinositides in spatiotemporal regulation of nuclear processes.

Project Summary

Project Title: The role of phosphoinositides in spatiotemporal regulation of nuclear processes.
Supervisor: Pavel Hozák

Project Description:
Phosphoinositides (PIPs) are recognized as regulators of many nuclear processes including chromatin remodeling, splicing, transcription, and DNA repair. These processes are spatially organized in different nuclear compartments. Various nuclear compartments are formed by entropy-driven mechanism – phase separation. The surface of such membrane-less structures spatiotemporally coordinates complex nuclear processes. The integration of PIPs into the surface of nuclear structures might therefore provide an additional step in their functional diversification by controlling the localization of different components, in a similar way as PIPs do in membranous cytoplasmic environment. This project focuses on deciphering the molecular mechanisms of various PIPs in establishing a dynamic nuclear architecture. In this project PhD candidate will characterize the PIPs-containing nuclear structures by combination of lipidomics, proteomics (quantitative MS), molecular biology (e.g. CRISPR/Cas9), biochemical and advanced microscopy (e.g. confocal, SIM, STED, FRAP) methods. The project is supported by funding from the Grant Agency of the Czech Republic.

Candidate Profile:
M.Sc. (Mgr.) degree or equivalent in molecular biology, biochemistry of biophysics. The candidate should be fluent in English, independent, with passion to science, willing to learn and develop new techniques.

Suggested reading:

  • Sobol, M., A. Krausova, S. Yildirim, I. Kalasova, V. Faberova, V. Vrkoslav, V. Philimonenko, P. Marasek, L. Pastorek, M. Capek, Z. Lubovska, L. Ulicna, T. Tsuji, M. Lisa, J. Cvacka, T. Fujimoto, and P. Hozak. 2018. Nuclear phosphatidylinositol 4,5-bisphosphate islets contribute to efficient RNA polymerase II-dependent transcription. J Cell Sci. 131.
  • Sztacho, M., M. Sobol, C. Balaban, S.E. Escudeiro Lopes, and P. Hozak. 2018. Nuclear phosphoinositides and phase separation: Important players in nuclear compartmentalization. Adv Biol Regul.
  • and references therein.

 

Vladimír Kořínek – Cell and Developmental Biology
www.img.cas.cz/research/vladimir-korinek
Project: Molecular mechanisms causing intestinal cancer – analyses at the single-cell level
Project: Molecular pathophysiology of myeloproliferative blood neoplasms

Projects Summary

Project Title: Molecular mechanisms causing intestinal cancer – analyses at the single-cell level
Supervisor: 

Project Description:
Intestinal carcinoma is one of the most frequent types of cancer in Western countries. Intestinal tumors evolve throughout a series of mutational events that produce considerable tumor cell heterogeneity. It is presumed that tumors in the initiation stages of the tumorigenic process – so-called microadenomas – are composed of highly proliferative cells displaying similar molecular and cell biology features. However, our recent results indicate that even early neoplastic lesions formed in the colon of experimental mice are composed of highly heterogeneous cell populations reminding of cell types present in the healthy colon epithelium. We aim to reveal the molecular mechanisms related to the observed tumor cell phenotypic heterogeneity. The research includes work with mouse transgenic models, analysis of gene expression at the single-cell level, and evaluation of the tumor cell epigenetic status. A part of the study will be performed using intestinal organoids derived from healthy or tumor tissue.

Candidate Profile:
Our laboratory is looking for a new, highly motivated team member with interest in biomedical research. The candidates should hold a Master degree in cellular and molecular biology, genetics or related fields. We expect that the prospective candidate is willing to learn advanced research techniques that include work with mouse tissues and human patient samples. We offer a friendly environment well-adjusted to the proposed research topic and decent financial conditions.

Suggested reading:

  • Krausova M, Korinek V. Wnt signaling in adult intestinal stem cells and cancer. Cell Signal. 2014 Mar;26(3):570-9. doi: 10.1016/j.cellsig.2013.11.032
  • Hrckulak D, Janeckova L et al. Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells. Genes (Basel). 2018 Sep 1;9(9). pii: E439. doi: 10.3390/genes9090439
  • Horazna M, Janeckova L et al. Msx1 loss suppresses formation of the ectopic crypts developed in the Apc-deficient small intestinal epithelium. Sci Rep. 2019 Feb 7;9(1):1629. doi: 10.1038/s41598-018-38310-y
  • Merenda A, Fenderico N et al. Wnt Signaling in 3D: Recent Advances in the Applications of Intestinal Organoids. Trends Cell Biol. 2019 Nov 9. pii:S0962-8924(19)30166-7. doi: 10.1016/j.tcb.2019.10.003

Project Title: Molecular pathophysiology of myeloproliferative blood neoplasms
Supervisor: Lucie Láníková

Project Description:
The aim of this project is the identification of the new genetic predispositions to myeloproliferative neoplasms (MPN) and their in vitro/vivo characterization, especially congenital weakly activating mutations in the JAK/STAT pathway. We propose to create a mouse model of prevalent germ-line Jak2 mutation and its cross-breeding with relevant MPN-like models. Reliable characterization of predisposing genetic variants based on analysis of the mouse model is the key step for improving the clinical diagnosis and prevention of hematologic malignancies. We will also identify and characterize new somatic mutations which cooperate or synergistically coexist with predisposing genetic variations in MPN.

Candidate Profile:
Our laboratory is looking for a new, highly motivated team member with interest in biomedical research. The candidates should hold a Master degree in cellular and molecular biology, genetics or related fields or have appropriate medical degree. We expect that the prospective candidate is willing to learn advanced research techniques that include work with mouse tissues and human patient samples. We would appreciate if the candidate is open-minded, with passion for science and eager to work in the lab. We offer a friendly environment well-adjusted to the proposed research topic and decent financial conditions.

Suggested reading:

  • Lanikova L. et al. Experimental Modeling of Myeloproliferative Neoplasms.Genes (Basel). 2019;10(10).
  • Stetka J. et al. Addiction to DUSP1 protects JAK2V617F-driven polycythemia vera progenitors against inflammatory stress and DNA damage, allowing chronic proliferation. Oncogene. 2019;38(28):5627-5642.
  • Mambet C. et al. Cooccurring JAK2 V617F and R1063H mutations increase JAK2 signaling and neutrophilia in myeloproliferative neoplasms. Blood. 2018;132(25):2695-2699.
  • Lanikova L. et al. Coexistence of gain-of-function JAK2 germ line mutations with JAK2V617F in polycythemia vera. Blood. 2016;128(18):2266-2270.

 

Zbyněk Kozmik – Transcriptional Regulation
www.img.cas.cz/research/zbynek-kozmik
Project: Evolution of eyes: insight from photoreceptors of invertebrate chordate amphioxus

Project Summary

Project Title: Evolution of eyes: insight from photoreceptors of invertebrate chordate amphioxus
Supervisor: Zbyněk Kozmik

Project Description:
Position is available in the area of evolutionary developmental biology (evo-devo). Project aims to provide new insight into evolution of animal eyes using invertebrate chordate amphioxus as a laboratory model. Project will specifically focus on amphioxus photoreceptors that are not associated with pigment cells: Joseph cells, bearing similarity to intrinsically photosensitive retinal ganglion cells of vertebrates, and lamellar body that is likely homologous to vertebrate pineal organ. The methods used will include basic bioinformatics analysis, gene isolation, gene expression studies by transcriptomics, whole-mount in situ hybridization and immunohistochemistry, biochemical characterization of photosensitive proteins (opsins) in vitro, characterization of selected gene knockouts produced in the lab by CRISPR/Cas9 system, and behavior visual tests (in collaboration with laboratory in Vienna).

Candidate Profile:
The laboratory of Trancriptional Regulation with a long-term experience in Developmental and Evolutionary Biology is searching for an enthusiastic and hard-working Ph.D student. We prefer self-motivated candidates with a strong commitment to experimental work. The candidate should hold a master degree in genetics, molecular biology, developmental biology, evolutionary biology or zoology. We offer a friendly and supporting environment in a state-of-the-art institution.

Suggested reading:

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. Amphioxus visual system is especially interesting because four types of receptors are involved in light detection – dorsal ocelli and Joseph cells (both rhabdomeric photoreceptors) and the frontal eye and lamellar body (both ciliary photoreceptors).

More here:
Amphioxus photoreceptors – insights into the evolution of vertebrate opsins, vision and circadian rhythmicity. Pergner J, Kozmik Z. Int J Dev Biol. 2017;61(10-11-12):665-681.

 

Libor Macůrek – Cancer Cell Biology
www.img.cas.cz/research/libor-macurek
Project: Exploring mechanisms of DNA replication restart upon collisions between transcription and replication

Project Summary

Project Title: Exploring mechanisms of DNA replication restart upon collisions between transcription and replication
Supervisors: Jana Dobrovolná, Pavel Janščák

Project Description:
Transcription-replication collisions (TRCs) represent a significant source of genomic instability in cells experiencing DNA replication stress. Although there is a great deal of knowledge about the strategies that cells evolved to avoid TRCs, understanding of how a replication fork restarts DNA synthesis upon a TRC remains elusive. Our recent studies have shown that replication restart upon R-loop-mediated TRCs relies on MUS81 endonuclease, RAD52 single-strand annealing protein and DNA ligase 4 (LIG4). In this project, we aim to use a proteomic approach to identify and functionally characterize new factors involved in this process. To study mechanisms of TCRs resolution after oncogene-induced replication stress we will also use advanced microscopic technics and genome wide sequencing (ChIP-seq).

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. Interest in bioinformatics is welcomed and we can open an extra position specifically for bioinformatician.

Suggested reading:

  • 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. (2019) Fork Cleavage-Religation Cycle and Active Transcription Mediate Replication Restart after Fork Stalling at Co-transcriptional R-Loops. Mol Cell. pii: S1097-2765(19)30804-4. doi: 10.1016/j.molcel.2019.10.026 (e-publeshed ahead of print)
  • Di Marco S, Hasanova Z, Kanagaraj R, Chappidi N, Altmannova V, Menon S, Sedlackova H, Langhoff J, Surendranath K, Hühn D, Bhowmick R, Marini V, Ferrari S, Hickson ID, Krejci L, Janscak P. (2017) RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis. Mol. Cell 66(5), 658-671
  • Urban V, Dobrovolna J, Hühn D, Fryzelkova J, Bartek J, Janscak P. (2016) RECQ5 helicase promotes resolution of conflicts between replication and transcription in human cells. J. Cell Biol. 214(4), 401-15.

 

Milan Reiniš – Immunological and Tumour Models
www.img.cas.cz/research/milan-reinis
Project: STAT3 signalling in tumour growth and immune suppression.

Project Summary

Project Title: STAT3 signalling in tumour growth and immune suppression.
Supervisor: Milan Reiniš

Project Description:
STAT3 signalling pathway provides an attractive target for therapeutic approaches in cancer. We can assume that inhibition of the STAT3 pathway can be a powerful tool for elimination of the detrimental effects of chemotherapy or to increase its effectiveness. The objective of this project is to evaluate the antitumour efficacy of existing and novel STAT3 inhibitors, including their additive/synergic effects in combination with chemotherapy or immunotherapy, as well as their effects on immune responses. We will also focus on the role of the STAT3 pathway in immunosuppressive cells of myeloid origin.

Candidate Profile:
We are looking for a motivated hard-working Ph.D. student, proficient in English, who will be able to closely collaborate with other lab members. The candidate should hold a master degree in molecular biology, cell biology, biochemistry or in a related field. Animal work using murine tumour models will be required. We offer a friendly and collaborative environment in a state-of-the-art institution.

Suggested reading:

  • Yu H, Lee H, Herrmann A, Buettner R, Jove R. Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nat Rev Cancer. 2014 14:736-46.
  • Mikyšková R, Indrová M, Polláková et al. Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloid-derived suppressor cells induced by growing TC-1 tumors. J Immunother. 2012 35:374-84.
  • Mikyskova R, Indrova M, Stepanek I et al. Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure inhibit prostate tumor growth in TRAMP mice. Oncoimmunology. 2017 24;6:e1362528.

 

David Staněk – RNA Biology
www.img.cas.cz/research/david-stanek
Project: Mutations in splicing factors linked with retina degeneration – molecular mechanism

Project Summary

Project Title: Mutations in splicing factors linked with retina degeneration – molecular mechanism
Supervisors: David Staněk

Project Description:
Retinitis pigmentosa (RP) is a human hereditary disorder caused by a progressive loss of photoreceptors. Surprisingly, mutations in six key splicing proteins have been associated with autosomal dominant form of RP. The mutated splicing factors are essential for every cell in a human body and thus it is enigmatic why their mutations have such a cell specific phenotype. In our laboratory, we have developed several model systems including mice and eye organoids to study how the RP-linked mutations in splicing factors affect target cell metabolism. The aim of the proposed PhD project is to characterize at molecular level, how RP-linked mutations change behavior of mutated proteins. Specifically, we plan to study how the mutations affect protein and RNA interactome of splicing factors in targeted cells and to identofy small molecules that could revert the observed phenotype.

Candidate Profile:
We seek an enthusiastic colleague with strong interest in RNA biology. Previous experience with molecular biology, cell culture or animal models is welcomed.

Requirements:

  • MSc, MRes, Diploma or an equivalent degree in Biology, Biomedicine, Chemistry or related sciences, to be obtained latest by the start of the fall term in September 2020
  • Practical experience in the lab working on scientific projects
  • Excellent English language skills and the desire to work in a dynamic international team

Suggested reading:

  • Krausova and Stanek (2017) snRNP proteins in health and disease. Semin Cell Dev Biol. DOI: 10.1016/j.semcdb.2017.10.011.
  • Ruzickova and Stanek (2017) Mutations in spliceosomal proteins and retina degeneration. RNA Biology. DOI: 10.1080/15476286.2016.1191735.

 

Petr Svoboda – Epigenetic Regulations
www.img.cas.cz/research/petr-svoboda
Project: Reviving canonical RNAi in mammals

Project Summary

Project Title: Reviving canonical RNAi in mammals
Supervisors: Petr Svoboda

Project Description:
The aim of the project is to examine different strategies for enhancing mammalian RNA interference in vivo.

Candidate Profile:
Curious,determined, open-minded, English-speaking, willing to work in a hard-working team. MSc. in molecular biology, developmental biology, cell biology or related areas. Experience with mice, micromanipulation, protein biochemistry or virology would be an advantage.

Suggested reading:

  • Liu Z, Wang J, Cheng H, Ke X, Sun L, Zhang QC, Wang HW. Cryo-EM Structure of Human Dicer and Its Complexes with a Pre-miRNA Substrate. Cell. 2018 May 17;173(5):1191-1203.e12.
  • Svoboda P: Renaissance of mammalian endogenous RNAi. FEBS Lett 2014 588(15): 2550-6.

 

Ondřej Štěpánek – Adaptive Immunity
www.img.cas.cz/research/ondrej-stepanek
Project: Cell communication in inflammation, autoimmunity and cancer

Project Summary

Project Title: Cell communication in inflammation, autoimmunity and cancer
Supervisors: Peter Dráber

Project Description:
Immune system has evolved to protect the body from invading pathogens and cancer, while preventing development of autoimmune diseases. In order to regulate ongoing inflammation, cells communicate with each other by producing cytokines. Cytokines are small proteins that bind to receptors on target cells and instruct them how to deal with ongoing infection. Defects in sensing cytokines can have grave implications for organism, ranging from immunodeficiency to autoimmunity. For example, cytokine TNF is critical to fight infection, but in pathological situations is responsible for the progression of rheumatoid arthritis or inflammatory bowel disease. Similarly, cytokine IL-17 can organize the immune system to protect from candidiasis, but is also highly involved in the progression of psoriasis. This project aims to uncover new molecular mechanisms how these and other crucial pro-inflammatory cytokines signal upon binding to their receptors and develop new approaches to modulate immune responses: either inhibit them in autoimmune diseases or enhance them in cancer.

Candidate Profile:
The present research will allow the candidate to learn a number of different experimental approaches, ranging from the study of protein complexes by mass-spectrometry, preparation of knockout cell lines via CRISPR/Cas9, analysis of signaling using methods of molecular biology and study of experimental mouse models. As such, the candidate should be deeply interested in science, proficient in English, willing to collaborate and share experience with colleagues, and willing to handle mouse work. The candidate should hold a master degree in immunology, cell biology, biochemistry, or a related field. Prior laboratory experience is advantageous.

The project will be carried at BIOCEV research campus. Candidates interested in this research should also contact Peter Draber directly at email: peter.draber@img.cas.cz.

Suggested reading:

  • Lafont et al. TBK1 and IKKε prevent TNF-induced cell death by RIPK1 phosphorylation. Nat Cell Biol. 2018 Dec;20(12):1389-1399.
  • Draber et al. LUBAC-Recruited CYLD and A20 Regulate Gene Activation and Cell Death by Exerting Opposing Effects on Linear Ubiquitin in Signaling Complexes. Cell Rep. 2015 Dec 15;13(10):2258-72.

 

Vladimír Varga – Laboratory of Cell Motility
www.img.cas.cz/research/vladimir-varga
Project: Construction of the mammalian primary cilium
Project: Flagellum distal end-localizing proteins of the human parasite Trypanosoma brucei

Projects Summary

Project Title: Construction of the mammalian primary cilium
Supervisor: Vladimír Varga

Project Description:
The primary cilium is an important organelle with signaling and sensory roles. The ciliary cytoskeleton is formed at its distal end, but little is known about the process and about proteins orchestrating it. Based on work on our model system, an experimentally highly tractable parasite Trypanosoma brucei, we recently identified novel mammalian proteins localizing to the distal end of the cilium. In the proposed project the function of these proteins will be studied. In particular, the possible role of the proteins in establishing the pattern of microtubules of different lengths in the cilium will be addressed by live cell imaging of wild type and mutant cell lines. In addition, murine knock-out models will be characterized. Advanced electron microscopy techniques will also be employed.

Candidate Profile:
We look for a highly motivated student eager to learn new techniques and eventually to drive the project. The candidate should hold a master degree in cell biology or related subjects. An experience with mammalian cell cultures or mice would be an advantage.

We are a young research group employing a broad range of approaches (cell biology, biochemistry, imaging)and we collaborate with leading scientists in the Czech Republic and abroad. The Institute of Molecular Genetics is a vibrant institution located in a modern building and offers superb research facilities.

Suggested reading:

  • Soares, H., Carmona, B., Nolasco, S., Viseu Melo, L., and Gonçalves, J. (2019). Cilia Distal Domain: Diversity in Evolutionarily Conserved Structures. Cells Feb 14;8(2).
  • Sun, S., Fisher, R.L., Bowser, S.S., Pentecost, B.T., and Sui, H. (2019). Three-dimensional architecture of epithelial primary cilia. Proc. Natl. Acad. Sci. 116, 9370–9379.
  • Varga, V., Moreira-Leite, F., Portman, N., and Gull, K. (2017). Protein diversity in discrete structures at the distal tip of the trypanosome flagellum. Proc. Natl. Acad. Sci. U. S. A. 114, E6546–E6555.

Project Title: Flagellum distal end-localizing proteins of the human parasite Trypanosoma brucei
Supervisor: Vladimír Varga

Project Description:
The flagellum is an organelle essential for cell motility with important signaling and sensory roles. Using an experimentally highly tractable protozoan Trypanosoma brucei, a causative agent of African sleeping sickness, we recently identified a number of flagellum distal end-localizing proteins involved in construction of the organelle, regulation of its motility and in cell morphogenesis. In the proposed project trypanosome cell lines mutant in the proteins will be characterized in detail. Biochemical approaches will be employed to gain a mechanistic insight into activities of the proteins. Advanced electron microscopy techniques will be employed to reveal their localization into particular flagellar structures.

Candidate Profile:
We look for a highly motivated student eager to learn new techniques and eventually to drive the project. The candidate should hold a master degree in cell biology or related subjects. An experience in molecular biology, eukaryotic microbes or electron microscopy would be an advantage.

We are a young research group employing a broad range of approaches (cell biology, biochemistry, imaging)and we collaborate with leading scientists in the Czech Republic and abroad. The Institute of Molecular Genetics is a vibrant institution located in a modern building and offers superb research facilities.

Suggested reading:

  • Varga, V., Moreira-Leite, F., Portman, N., and Gull, K. (2017). Protein diversity in discrete structures at the distal tip of the trypanosome flagellum. Proc. Natl. Acad. Sci. U. S. A. 114, E6546–E6555.
  • Soares, H., Carmona, B., Nolasco, S., Viseu Melo, L., and Gonçalves, J. (2019). Cilia Distal Domain: Diversity in Evolutionarily Conserved Structures. Cells Feb 14;8(2).
  • Abeywickrema, M., Vachova, H., Farr, H., Mohr, T., Wheeler, R.J., Lai, D.-H., Vaughan, S., Gull, K., Sunter, J.D., and Varga, V. (2019). Non-equivalence in old- and new-flagellum daughter cells of a proliferative division in Trypanosoma brucei. Mol. Microbiol. 112(3):1024-1040.

Last change: January 10, 2020