Přehled

PhD Coordinator: Mgr. Martin Horák, Ph.D.
e-mail: martin.horak@iem.cas.cz, tel.: +420 241 063 623

Institute of Experimental Medicine CAS supports basic research across the biomedical spectrum with a high potential for technological transfer in human medicine. Our projects are focused on biomedical challenges such as finding effective diagnostic markers and treatment of serious diseases associated with aging of the human population – neurodegeneration, trauma/ischemia, musculoskeletal disorders, cancer, degenerative changes in vision and hearing. Strong impact is also given on the assessment of environmental pollution on human health.

Apply here: PhD application

Open PhD positions at the Institute of Experimental Medicine CAS, v. v. i. for Academic Year 2020/2021

Delineating the mechanisms that regulate NMDA receptors in mammallian neurones

Laboratory: Department of Neurochemistry
Group Leader: Martin Horak, PhD.
Website: http://www.iem.cas.cz/en/research/departments/department-of-neurochemistry/

Project summary

Supervisor: Martin Horak
Project title: 
Delineating the mechanisms that regulate NMDA receptors in mammallian neurones

Project description:
N-methyl-D-aspartate receptors (NMDARs) are a subclass of glutamate receptors that play an essential role in excitatory neurotransmission in the mammalian brain. NMDARs are tetrameric protein complexes composed of GluN1, GluN2, and GluN3 subunits, which can assemble in a variety of combinations. In this Ph.D. project, you will combine state-of-the-art molecular biology, biochemistry, immunocytochemistry and electrophysiology, with unique mice models in order to identify: i) which structural determinants in GluN subunits and NMDAR ligands regulate the surface delivery, mobility, and stability of NMDARs; and ii) how specific NMDARs and their ligands contribute to neurodegenerative conditions.

Candidate profile:
M.Sc. (Mgr.) degree or equivalent in (bio)chemistry, molecular/cellular biology, medicine or physiology; strong interest in basic neuroscience research.

Suggested reading:
• Hemelikova et al. Neuropharmacology 157:107671 (2019).
• Skrenkova et al. Scientific Reports 9(1):12303 (2019).
• Kaniakova et al. Neuropharmacology 140:217-232 (2018).
• Skrenkova et al. Front Mol Neurosci 11:188 (2018).
• Lichnerova et al. J Biol Chem 290(30):18379-90 (2015).
• Kaniakova et al. J Biol Chem 287(31):26423-34 (2012).
• Horak et al. J Neurosci 28(13):3500-9 (2008).

Develop novel pharmacological compounds that act on NMDA receptors

Laboratory: Department of Neurochemistry
Group Leader: Martin Horak, PhD.
Website: http://www.iem.cas.cz/en/research/departments/department-of-neurochemistry/

Project summary

Supervisor: Martin Horak
Project title: 
Develop novel pharmacological compounds that act on NMDA receptors

Project description:
In collaboration with the Biomedical Research Center in Hradec Kralove and the National Institute of Mental Health in Klecany, we will develop a series of tacrine-based compounds that act on NMDA receptors via a unique mechanism. In this Ph.D. project, you will investigate the mechanisms of action of novel compounds that modulate NMDA receptors using sophisticated electrophysiological approaches with HEK293 cells and cultured hippocampal neurons. Our goal is to optimise the physico-chemical properties of novel compounds, including their solubility and blood–brain barrier permeability, in order to treat cognitive deficits.

Candidate profile:
M.Sc. (Mgr.) degree or equivalent in (bio)chemistry, molecular/cellular biology, medicine or physiology; strong interest in applied neuroscience research.

Suggested reading:
• Hemelikova et al. Neuropharmacology 157:107671 (2019).
• Kaniakova et al. Curr Alzheimer Res 16(9):821-833 (2019).
• Kaniakova et al. Neuropharmacology 140:217-232 (2018).
• Gazova et al. Biochim Biophys Acta Mol Basis Dis 1863(2):607-619 (2017).
• Horak et al. Prog Neuropsychopharmacol Biol Psychiatry 75:54-62 (2017).

Processing of complex acoustical signals in neuronal circuits of the central auditory system

Laboratory: Auditory neuroscience
Group Leader: Rostislav Tureček, Ph.D.
Website: http://www.iem.cas.cz/vyzkum/oddeleni/oddeleni-neurofyziologie-sluchu/

Project summary

Supervisor: Assoc. Prof. Daniel Šuta, Ph.D.
Project title:
 Processing of complex acoustical signals in neuronal circuits of the central auditory system

Project description:
Complex sounds” are sounds that are more complicated than a pure tone or white noise. Most behaviorally relevant sounds fall into this category, including communication sounds like human speech and environmental sounds. Acoustical signals are processed successively in the individual stages of the auditory pathway from the auditory nerve to the auditory cortex. The aim of the project is
to analyze coding of complex sounds including animal communication sounds in neuronal circuits of the auditory cortex and subcortical nuclei of the auditory system and study the effects of factors such as background noise, aging or noise exposure.

Candidate profile:
Conducted research is based on a multidisciplinary approach including behavioral tests, electrophysiological and optical recording of neural activity or computational modelling. We are looking for a highly motivated candidate with background in the field of medicine, biology or engineering (or related), who is interested in some of these methods and eager to get involved in cutting edge, creative research. You will be part of a team of academic researchers working on state of the art technologies and have the chance to contribute to and participate in the international research community. Good communication skills and teamwork are expected. Basic programming skills are beneficial.

Suggested reading:
King AJ, Teki S and Willmore BDB. Recent advances in understanding the auditory cortex. F1000Research 2018, 7 (F1000 Faculty Rev):1555 (https://doi.org/10.12688/f1000research.15580.1)
Šuta D, Popelář J, Burianová J, Syka J. (2013) Cortical representation of species-specific vocalizations in guinea pig. PLoS One. 2013 Jun 13;8(6):e65432.
Rybalko N, Šuta D, Popelář J, Syka J. Inactivation of the left auditory cortex impairs temporal discrimination in the rat. Behav Brain Res. 2010; 209(1): 123-30.

Understanding the factors critical for successful paternal genome remodelling

Laboratory: Dept. of Developmental Biology
Group Leader: RNDr. Ondřej Machoň, Ph.D.
Website: http://www.iem.cas.cz/en/research/departments/department-of-developmental-biology/

Project summary

Supervisor:Helena Fulkova, Ph.D.
Project title:
Understanding the factors critical for successful paternal genome remodelling

Project description:
The emergence of the nucleus is a major evolutionary event that discriminated eukaryotes from prokaryotes. It is a hallmark of nearly all eukaryotic cells and central to their function. Aberrations in the nuclear composition and structure are linked to diseases such as cancer. The project is focused on how cells build a nucleus from different genomic substrates and what is the consequence of nuclear dysregulation, with the ultimate goal of elucidating the function of the nucleus as an essential cellular structure. While many theories exist, it is extremely difficult to assess these in tissue culture cells. Early embryos offer a unique opportunity to study these phenomena: Oocytes build a nucleus from a practically naked DNA (sperm), and also two morphologically and functionally different nuclei (maternal and paternal) co-exist in a common cytoplasm after fertilisation. In contrast to egg extracts, this system offers an unprecedented chance to rigorously test the consequence of targeted nuclear dysregulation through the ability of embryos to give rise to live animals.

Candidate profile:
We are looking for a highly motivated student to work in a dynamic and competitive environment. Background in molecular biology, biochemistry methods, reproductive or developmental biology and/or micromanipulations is welcomed. Good background in microscopy and epigenetics is advantageous. Strong motivation to learn, adapt and develop new methods is a must. The position will require the successful candidate to work with animals (mouse) and animal material. The candidate should show good English skills as exchange of students/staff with Japanese laboratories throughout the project will be required (strong working ethics desirable).

Suggested reading:
Dissecting the role of the germinal vesicle nuclear envelope and soluble content in the process of somatic cell remodelling and reprogramming. J Reprod Dev. 2019 Oct 23;65(5):433-441.
Nucleoli in embryos: a central structural platform for embryonic chromatin remodeling? Chromosome Res. 2019 Mar;27(1-2):129-140.
The maternal nucleolus plays a key role in centromere satellite maintenance during the oocyte to embryo transition. Development. 2014 Apr;141(8):1694-704.

The maternal nucleolus is essential for early embryonic development in mammals. Science. 2008 Feb 1;319(5863):613-6.

Eisosomal binding of Xrn1 in regulation of mRNA metabolism

Laboratory: Functional Organization of Biomembranes
Group Leader: Assoc. Prof. Jan Malinsky, PhD.
Website: http://iem.cas.cz/en/research/departments/department-of-functional-organization-of-biomembranes/

Project summary

Supervisor:Jan Malinsky
Project title:
Eisosomal binding of Xrn1 in regulation of mRNA metabolism

Project description:
Project will be focused on mechanisms of Xrn1 association with specialized microdomains at the plasma membrane under conditions of chronic glucose deprivation of yeast and consequences of this enzyme sequestration on the cellular pool of mRNA. Experiments conducted by the candidate should contribute to understanding the involvement of plasma membrane microdomains in the stress adaptation of the cellular metabolism. Developmental conservation of Xrn1 in general and its segregation upon metabolic stimuli in particular suggest wide impact of the expected results.

Candidate profile:
– working experience in the field of molecular and cell biology with a genuine interest in biochemical processes and/or biological functions associated with cellular membranes
– basic skills in molecular biology techniques and an interest in fluorescence microscopy

Suggested reading:
Malinsky J, Opekarová M. New Insight Into the Roles of Membrane Microdomains in Physiological Activities of Fungal Cells. In: Kwang Jeon, International Review of Cell and Molecular Biology 325:119-180, ISBN:978-0-12-804806-1, Elsevier Inc. Academic Press (2016).
Vaskovicova K, Awadova T, Vesela P, Balazova M, Opekarová M, Malinsky J. mRNA decay is regulated via sequestration of the conserved 5’-3’ exoribonuclease Xrn1 at eisosome in yeast. Eur J Cell Biol 96(6):591-599 (2017).

Role of eisosome in stress response regulation

Laboratory: Functional Organization of Biomembranes
Group Leader: Assoc. Prof. Jan Malinsky, PhD.
Website: http://iem.cas.cz/en/research/departments/department-of-functional-organization-of-biomembranes//

Project summary

Supervisor: Jan Malinsky
Project title: 
Role of eisosome in stress response regulation

Project description:
Project will be focused on elucidation and further characterization of the stress-related phenotype of the yeast cells defective in formation a specialized plasma membrane microdomain, MCC/eisosome. Effect of eisosome loss on the expression profile of the cell under various stress conditions will be analyzed and matched with known connections of the eisosome to conserved regulatory pathways, with a special emphasis on lipid metabolism regulation.

Candidate profile:
– working experience in the field of molecular and cell biology with a genuine interest in biochemical processes and/or biological functions associated with cellular membranes
– basic skills in molecular biology techniques and an interest in fluorescence microscopy

Suggested reading:
Malinsky J, Opekarová M. New Insight Into the Roles of Membrane Microdomains in Physiological Activities of Fungal Cells. In: Kwang Jeon, International Review of Cell and Molecular Biology 325:119-180, ISBN:978-0-12-804806-1, Elsevier Inc. Academic Press (2016).
Zahumensky J, Malinsky J. Role of MCC/Eisosome in Fungal Lipid Homeostasis. Biomolecules 9(8): pii: E305. doi: 10.3390/biom9080305 (2019).

Development of smart scaffolds for soft tissues

Laboratory: Department of Tissue Engineering
Group Leader: Eva Filová, MSc., Ph.D.
Website: http://www.iem.cas.cz/en/research/departments/department-of-tissue-engineering/

Project summary

Supervisor: Eva Filová, Ph.D.
Project title: 
Development of smart scaffolds for soft tissues

Project description:
Materials for wound healing should regenerate the full thickness defects and restore the tissue function. They should support cell growth, production of extracellular matrix, vascularization and prevent bacterial contamination. The scaffolds should mimic the structure of the tissue and should deliver bioactive substances for the enhancing of regeneration. The scaffold will be developed as two-dimensional and three-dimensional systems delivering growth factors or other bioactive molecules and will be tested with skin cells and stem cells including iPSCs. Moreover, a 3D in vitro model will be established. The project is supported by both national and international projects and enables cooperation with different international laboratories.

Candidate profile:
Graduate of the University (e.g. Faculty of Medicine, Pharmaceutical Faculty, Faculty of Science, Czech Technical University) with a background of biology, biochemistry, or molecular chemistry, physiology.

Suggested reading:
Babrnáková J, et al. Materials Science and Engineering: C, 2019 July: 100. Pages 236-246.
Vocetkova, K., et al. RSC ADVANCES 2017: 7(85). Pages: 53706-53719
Rampichova, M., et al. Cell Adhesion & Migration 2018: 12(3), Pages: 271-285 1933-6918
Sovkova V, et al. Platelets. 2017 Jun 26:29(4).Pages 395-405.
Buzgo M, et al. . J Tissue Eng Regen Med. 2017: 12(3), Pages 583-597
Buzgo M, et al. Regenerative Medicine. Regen Med. 2019 May;14(5):423-445. ISSN : 1746-0751

The role of TRPV4 channels in oligodendrogenesis after ischemic brain injury

Laboratory: Department of Cellular Neurophysiology
Group Leader: Miroslava Anděrová, PhD.
Website: http://www.iem.cas.cz/en/research/departments/department-of-cellular-neurophysiology/

Project summary

Supervisor: Miroslava Anděrová, PhD.
Project title: 
The role of TRPV4 channels in oligodendrogenesis after ischemic brain injury

Project description:
TRPV4 nonselective cation channels are members of the TRP (transient receptor potential) channel superfamily, which are broadly expressed throughout the nervous system in neurons and several glia subpopulations, including NG2 glia. NG2 glia, also called oligodendrocyte precursor cells are the key source of myelinating oligodendrocytes and TRPV4 mediated calcium signaling has been suggested to play a role in the activation of myelin repair (re-myelination) after the pathological damage of myelin sheath. The aim of the project will be to characterize a role of TRPV4 channels in regenerative processes after ischemic brain injury, and to evaluate the influence of these channels on oligodendrogenesis in the ischemic brain. To achieve these aims, laboratory techniques, such as imunofluorescence, patch-clamp, fluorescence-activated cell sorting, and RNA-Seq analysis will be performed on specimens isolated from control and conditional Trpv4 knockout mice.

Candidate profile:
A successful candidate should:

– have a master’s degree in biological, medical, or related field
– have good working knowledge of English language
– be willing to work with laboratory animals (mice)
– be interested in learning new laboratory techniques
– be able to work independently as well as in a team

Suggested reading:
Valny, M., et al.: A single-cell analysis reveals multiple roles of oligodendroglial lineage cells during post-ischemic regeneration. Glia. 2018 May;66(5):1068-1081. doi: 10.1002/glia.23301. Epub 2018 Feb 2.
Ohashi, K., et al.: TRPV4 is functionally expressed in oligodendrocyte precursor cells and increases their proliferation. Pflugers Arch. 2018 May;470(5):705-716. doi: 10.1007/s00424-018-2130-3. Epub 2018 Mar 22.
Liu, M., et al.: TRPV4 Inhibition Improved Myelination and Reduced Glia Reactivity and Inflammation in a Cuprizone-Induced Mouse Model of Demyelination. Front Cell Neurosci. 2018 Nov 5;12:392. doi: 10.3389/fncel.2018.00392. eCollection 2018.

Horizontal transfer of mitochondria in brain tumour formation

Laboratory: Department of Cellular Neurophysiology
Group Leader: Miroslava Anděrová, PhD.
Website: http://www.iem.cas.cz/en/research/departments/department-of-cellular-neurophysiology/

Project summary

Supervisor: Miroslava Anděrová, PhD.
Project title: 
Horizontal transfer of mitochondria in brain tumour formation

Project description:
Mitochondria are semi-autonomous organelles with a role in cell bioenergetics and cell death regulation. This project builds on in vivo observations of horizontal transfer of these dynamic organelles in cancer, which may be important in tumour formation and progression. Here, we will investigate inter-cellular mitochondrial transfer in glioblastoma multiforme, one of the most difficult-to-treat cancers. Our main goals will be to explore the functional consequences of this phenomenon and its link to tumour formation, and to determine the molecular mechanisms implicated in this process. To fulfil these goals, we will establish brain tumour animal models. In order to better monitor the formation of tumours, we will utilize stereofluorescence microscopy employing cranial window implants.

Candidate profile:
A successful candidate should:

– have a master’s degree in biological, medical, or related field
– have good working knowledge of English language
– be willing to work with laboratory animals (mice)
– be interested in learning new laboratory techniques
– be able to work independently as well as in a team

Suggested reading:
Tan et al.: Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA. Cell Metab. 2015 Jan 6;21(1):81-94. doi: 10.1016/j.cmet.2014.12.003.
Dong et al.: Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells. Elife. 2017 Feb 15;6. pii: e22187. doi: 10.7554/eLife.22187.
Osswald et al.: Brain tumour cells interconnect to a functional and resistant network. Nature. 2015 Dec 3;528(7580):93-8. doi: 10.1038/nature16071. Epub 2015 Nov 4.

The role of TRPV4 channels in brain edema formation

Laboratory: Department of Cellular Neurophysiology
Group Leader: Miroslava Anděrová, PhD.
Website: http://www.iem.cas.cz/en/research/departments/department-of-cellular-neurophysiology/

Project summary

Supervisor: Miroslava Anděrová, PhD.
Project title: 
The role of TRPV4 channels in brain edema formation

Project description:
TRPV4 nonselective cation channels are members of the TRP (transient receptor potential) channel superfamily. Due to their broad expression throughout the nervous system and different ways of their activation, TRPV4 channels are involved in a wide range of physiological and pathological processes. Besides a number of neuronal populations, their expression has been reported in several glial subpopulations, namely in endothelial cells, microglia, astrocytes, and oligodendrocyte precursor cells (OPCs or NG2 glia). The aim of the project will be to characterize cell-type-specific roles of TRPV4 channels in brain edema formation, to assess the role of astrocytic TRPV4 channels in regenerative processes after ischemic brain injury. To achieve these aims, laboratory techniques, such as three-dimensional morphometry, fluorescence-activated cell sorting, and RNA-Seq analysis will be performed on specimens isolated from control and conditional Trpv4 knockout mice.

Candidate profile:
A successful candidate should:

– have a master’s degree in biological, medical, or related field
– have good working knowledge of English language
– be willing to work with laboratory animals (mice)
– be interested in learning new laboratory techniques
– be able to work independently as well as in a team

Suggested reading:
Pivonkova et al.: The Contribution of TRPV4 Channels to Astrocyte Volume Regulation and Brain Edema Formation. Neuroscience. 2018 Dec 1;394:127-143. doi: 10.1016/j.neuroscience.2018.10.028. Epub 2018 Oct 24.
Butenko et al.: The increased activity of TRPV4 channel in the astrocytes of the adult rat hippocampus after cerebral hypoxia/ischemia. PLoS One. 2012;7(6):e39959. doi: 10.1371/journal.pone.0039959. Epub 2012 Jun 27.
Benfenati et al.: Expression and functional characterization of transient receptor potential vanilloid-related channel 4 (TRPV4) in rat cortical astrocytes. Neuroscience. 2007 Sep 21;148(4):876-92. Epub 2007 Jul 17.

Drug delivery systems for treatment of osteoporotic fractures

Laboratory: Department of Tissue Engineering
Group Leader: Mgr. Eva Filová, Ph.D.
Website: http://www.iem.cas.cz/en/research/departments/department-of-tissue-engineering/

Project summary

Supervisor: Mgr. Věra Sovková, Ph.D.
Project title: 
Drug delivery systems for treatment of osteoporotic fractures

Project description:
The project aims to develop a strategy for the therapy of osteoporosis . The conventional systems for filling
large defects will be enriched by a nanoencapsulated formulation containing osteoclastogenesis inhibitors suppressing
degradation of a newly formed bone, resulting in improved healing. The scaffolds will be tested in vitro and in vivo. The project is supported by the national and international projects and enables cooperation with different international laboratories.

Candidate profile:

  • M.Sc. (Mgr.) degree or equivalent (e.g. Faculty of Medicine, Pharmaceutical Faculty, Faculty of Science, Biomedical Engineering) with a background in biology, biochemistry, molecular chemistry, or physiology
  • Work experience in the field of molecular biology and cell culture
  • Knowledge of basic laboratory and aseptic techniques

Suggested reading:
Benisch, P., Schilling, T., Klein-Hitpass, L., Frey, S.P., Seefried, L., Raaijmakers, N., Krug, M.,
Regensburger, M., Zeck, S., Schinke, T., Amling, M., Ebert, R., Jakob, F., 2012. The transcriptional
profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows
overexpression of osteogenic inhibitors. PLoS One. 7(9):e45142
Buzgo, M., Rampichova, M., Vocetkova, K., Sovkova, V., Lukasova, V., Doupnik, M., Mickova, A.,
Rustichelli, F., Amler, E., 2017. Emulsion centrifugal spinning for production of 3D drug releasing
nanofibres with core/shell structure. RSC Advances 7, 1215-1228.
Silverman, S.L., Kupperman, E.S., Bukata, S.V., 2016. Fracture healing: a consensus report from the
International Osteoporosis Foundation Fracture Working Group. Osteoporosis International 27,
2197-2206.