IEM
We appreciate your interest in studying and working at the Institute of Experimental Medicine of the Czech Academy of Sciences.
For more information, please visit our website: http://www.iem.cas.cz/iem/phd/ (Application start in February 2022)
We are looking forward to hearing from you.
Open PhD positions for Academic Year 2022/2023
Department: Department of Cellular Neurophysiology
Head: 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 and AQP4 channels in ischemic brain injury and subsequent regeneration
Project description:
TRPV4 nonselective cation channels are members of the TRP (transient receptor potential) channel superfamily, and are broadly expressed throughout the nervous system in neurons and several glia subpopulations, including astrocytes, NG2 glia and microglia. Due to this broad expression and their different methods of activation, TRPV4 channels are involved in numerous physiological and pathological processes. They are also suspected of cooperation with other channels found on cellular membranes, such as Aquaporin 4 (AQP4). The aim of the project will be to characterize cell-type-specific roles of TRPV4 and AQP4 channels in pathological processes, and to evaluate the influence of these channels on ischemic brain injury and regenerative processes. To achieve these aims, laboratory techniques, such as immunofluorescence, patch-clamp, fluorescence-activated cell sorting, and RNA-Seq analysis will be performed on specimens isolated from control and conditional Trpv4 and AQP4 knockout mice.
Candidate profile:
A successful candidate should:
- have a master’s degree in a biological, medical, or related field
- have good working knowledge of the 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:
Kirdajova et al.: Transient astrocyte-like NG2 glia subpopulation emerges solely following permanent brain ischemia. Glia. 2021 Nov;69(11):2658-2681. doi: 10.1002/glia.24064. Epub 2021 Jul 27.
Androvic et al.: Decoding the Transcriptional Response to Ischemic Stroke in Young and Aged Mouse Brain. Cell Rep. 2020 Jun 16;31(11):107777. doi: 10.1016/j.celrep.2020.107777.
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.
Department: Neurochemistry
Head: Martin Horak
Website: http://www.iem.cas.cz/en/research/departments/department-of-neurochemistry/
Project summary
Supervisor: Martin Horak
Project title: The development of novel pharmacological compounds acting on NMDA receptors
Project description:
N-methyl-D-aspartate (NMDA) receptors belong to a family of ionotropic glutamate receptors that play a key role in excitatory neurotransmission in the mammalian central nervous system. Alternatively, their dysfunction leads to many neuropathological disorders including neurodegenerative diseases and cognitive deficits. 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 compounds based on tacrine and MK-801 that modulate NMDA receptor activity by a unique mechanism. In this PhD project, you will investigate the molecular mechanisms of the modulatory effect of the novel compounds on NMDA receptors, using sophisticated molecular biological and electrophysiological approaches including, for example, whole-cell and single-channel measurements on transfected HEK293 cells, as well as synaptic measurements on autaptic hippocampal neurons infected with lentiviruses expressing mutated GluN subunits. Our goal is to optimize the physicochemical properties of the novel compounds, including their solubility, blood-brain barrier permeability, affinity and rate of action on individual NMDA receptor subtypes, but to minimize their side effects in vivo.
Candidate profile:
M.Sc. (Mgr.) degree or equivalent in (bio)chemistry, molecular/cellular biology, neuroscience, physiology or medicine; strong interest in conducting pre-clinical research in the field of glutamate receptors.
Suggested reading:
• Kolcheva et al., Neuropharmacology 189:108528 (2021).
• Gorecki et al., Eur J Med Chem 219:113434 (2021).
• Kaniakova et al., Biochem Pharmacol 186:114460 (2021).
• 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).
Department: Developmental Biology
Head: Ondrej Machon
Website: http://www.iem.cas.cz/en/research/departments/department-of-developmental-biology/
Project summary
Supervisor: Ondrej Machon
Project title: Molecular interactions of nerve-associated cells with dermal placodes
Project description:
The project will study the interactions of neural crest-derived cranial nerves with epithelial structures, such as developing teeth, hair or salivary glands. We aim to reveal signals from cranial nerves and nerve-associated cells that initiate the formation of epithelial placodes corresponding to the mentioned organs. The experiments are carried out in transgenic mouse models based on tissue-specific gene inactivation in the neural crest. All required mouse strains are already available in our lab and preliminary tests have been initiated.
Candidate profile:
M.Sc. (Mgr.) degree or equivalent in molecular/cellular biology or biochemistry; strong interest in developmental and molecular biology
Suggested reading:
- O. Machon, J. Masek, O. Machonova, S. Krauss, Z. Kozmik, BMC. Dev. Biol. 15:40 (2015).
- J. Fabik, K. Kovacova, Z. Kozmik, O. Machon, Biol. Open. 9:6 (2020).
- I. Adameyko, K. Fried, Front. Physiol. 7:49 (2016)
- N. Kaukua et al., Nature 513:7519 (2014)
- M. Kaucka et al., Cell. Mol. Life Sci. 78:16 (2021)
Department: Auditory Neuroscience
Head: Rostislav Turecek, PhD.
Website: http://www.iem.cas.cz/en/research/departments/department-of-auditory-neuroscience/
Project summary
Supervisor: Rostislav Turecek, PhD.
Project title: The role of inhibitory GABAb receptors in the auditory pathways, and age-related hearing loss
Project description:
The gamma-aminobutyric acid type B receptor (GABAb) is a G-protein coupled receptor for GABA, a major inhibitory transmitter in the mammalian nervous system. Neurons of the auditory pathway generally show high levels of GABAb expression, yet the role of these receptors in the mechanisms of auditory function is not well understood. Since changes in inhibition have been found to be associated with various forms of hearing loss, GABAb dysfunction is also expected to play a role in some pathologies of the auditory system. The aim of the project is to reveal the action of GABAb receptors in the neural circuits of subcortical and cortical auditory areas of adult and aging mammals. Experimental work will include advanced in vivo and in vitro electrophysiological methods, in vivo Ca2+ imaging using two-photon microscopy, and immunohistochemical and behavioral techniques applied to mouse models of hearing disorders such as presbycusis and tinnitus. After learning the basics of these techniques, we expect the candidate to specialize in a chosen method.
Candidate profile:
A successful candidate should:
- have a Master’s degree in Biology, Biomedical Science or related field
- have a deep interest in biomedical research, enthusiasm and high motivation to learn new laboratory techniques, and a commitment to hard work
- have a good command of spoken and written English
- be willing to work with laboratory animals (rodents)
- have good communication skills and be able to work in a team
Suggested reading:
Schwenk J et al.: Native GABAB receptors are heteromultimers with a family of auxiliary subunits. Nature 465: 231-235, 2010.
Turecek R et al.: Auxiliary GABAB receptor-subunits uncouple G-protein βγ-subunits from effector channels to induce desensitization. Neuron, 82: 1032-1044, 2014.
Terunuma M: Diversity of structure and function of GABAB receptors: a complexity of GABAB-mediated signaling. Proc. Jpn. Acad., Ser. B 94: 390-411, 2018.
Henton A, Tzounopoulos T: What’s the buzz? The neuroscience and the treatment of tinnitus. Physiol. Rev. 101: 1609-1632, 2021.
Studer F, Barkat TR: Inhibition in the auditory cortex. Neurosci. Biobehav. Rev. 132: 61-75, 2021.
Department: Neuroregeneration
Head: Assoc.Prof Pavla Jendelova, PhD
Website: http://www.iem.cas.cz/en/research/departments/department-of-neuroregeneration/
Project summary
Supervisor: Jiri Ruzicka, PhD.
Project title: The role of sulfation epitopes of brain extracellular matrix in aging and neurodegeneration
Project description:
This PhD project aims to understand the role of Chondroitin sulphate transferase 11 (Chst11) in brain extracellular matrix (ECM), and particularly perineuronal nets (PNNs), in aging and neurodegeneration. The project follows a Chst11 knock out study (Chst11ko) in young mice.
Chondroitin sulphate proteoglycan, sulphated at the C4 epitope (in majority by Chst11), form more rigid ECM in comparison with other epitopes. This leads to a less plastic state, with lower probability of synapse formation and decreased mobility of receptors and ion channels, especially in PNN+ neurons. A major increase of C4 sulfation is observed in aging, when it dominates over other more plastic forms. According to the latest research, this could be one of the reasons for cognitive decline in the elderly population.
Using Chst11ko mice we will monitor behavioral changes in aging or tauopathy mice, with the main focus being on short or long-term memory and cognitive flexibility. Moreover, sociability, anxiety and general locomotor function will be measured. Structures of ECM/PNNs will be monitored using biochemical and immunohistochemical analysis. The changes in synaptic connectivity and activity will be measured using several techniques such as super-resolution microscopy, electrophysiology, or proteomics.
Candidate profile:
For this position we are seeking a motivated student with an interest in neuroscience. Since the project is based on animal experiments, a positive attitude toward animals is necessary. Additionally, previous experience with behavioral neuroscience would be a great advantage. At least basic knowledge of proteomics, qPCR and microscopy techniques is desirable. English at the level B2/C1 is required.
Suggested reading:
Foscarin et al., Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory. Aging (Albany NY). 2017 Jun 28;9(6):1607-1622. doi: 10.18632/aging.101256. PMID: 28657900; PMCID: PMC5509459.¨
Yang et al., Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Mol Psychiatry. 2021 Jul 16. doi: 10.1038/s41380-021-01208-9. Epub ahead of print. PMID: 34272488.
Yang et al., Antibody recognizing 4-sulfated chondroitin sulfate proteoglycans restores memory in tauopathy-induced neurodegeneration. Neurobiol Aging. 2017 Nov;59:197-209. doi: 10.1016/j.neurobiolaging.2017.08.002. Epub 2017 Aug 9. PMID: 28890301.
Ruzicka et al., PNNs affecting memory retention after synapse withdrawal. Preprint: https://www.biorxiv.org/content/10.1101/2021.04.13.439599v1
Department: Neurochemistry
Head: Martin Horak
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 mammalian neurons
Project description:
N-methyl-D-aspartate receptors (NMDARs) are a subclass of glutamate ion channels that play a critical role in excitatory neurotransmission in the mammalian brain. For this PhD project, you will study the molecular mechanisms that i) regulate the early transport of NMDARs from the endoplasmic reticulum to the neuronal surface, and ii) regulate the surface mobility and synaptic localization of individual NMDAR subtypes. To do this, you will combine advanced molecular biology approaches including lentiviral preparation, biochemistry including Western blotting and co-immunoprecipitation, live microscopy including quantum dot tracking of NMDARs, super-resolution microscopy approaches including dSTORM and SIM combined with nanobodies, and electrophysiology in autaptic hippocampal neurons from unique knock-out mouse models.
Candidate profile:
M.Sc. (Mgr.) degree or equivalent in (bio)chemistry, molecular/cellular biology, neuroscience, physiology or medicine; strong interest in conducting basic research in the field of glutamate receptors.
Suggested reading:
• Kolcheva et al., Neuropharmacology 189:108528 (2021).
• Skrenkova et al., Scientific Reports 10(1):18576 (2020).
• 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).
Department: Cell Nucleus Plasticity
Head: Helena Fulkova, Ph.D.
Website: http://iem.cas.cz/en/research/departments/department-of-cell-nucleus-plasticity/
Project summary
Supervisor: Helena Fulkova, Ph.D.
Project title: Molecular and functional analysis of the nucleolus in 3D genome organization in early embryo development
Project description:
Eukaryotic genomes exhibit a complex 3D architecture, important for the correct execution of gene expression programs. Together with the nuclear periphery, the nucleolus is a major genome organizing structure. Upon fertilization, the parental genomes undergo an extensive spatial and epigenetic remodeling to establish totipotency. How the nucleolus participates in the 3D genome organization and correct execution of the developmental program is unknown. The aim of the project is to determine the role of embryonic nucleoli in early development using a synergistic multi-omics approach with focus on the novel Nucleolar-DamID technology to identify and functionally characterize parental genomic domains contacting the nucleolus in embryos. By artificially tethering specific sequences to nucleoli using a CRISPR/Cas9-based system, we will determine the molecular and functional contribution of nucleoli to 3D genome organization in development. The results will widen our molecular understanding of early development and provide information of high medical relevance, especially for reproductive medicine. The project will be conducted in collaboration with the University of Zurich, Switzerland.
Candidate profile:
We are looking for a highly motivated student to participate in this challenging project. The skills required are; intermediate level methods in molecular biology, good knowledge of and experience in developmental and/or reproductive biology. A background in micromanipulations and confocal microscopy would be beneficial. The candidate should demonstrate strong work ethics and thrive in a highly competitive environment. Independent thinking, a strong motivation to learn, adapt and develop new methods is a must. The position will require the successful candidate to work with animals (mice) and animal material. The candidate should have good English skills as exchange of students/staff with foreign laboratories throughout the project will be required. Good communication skills is a necessity due to the collaborative nature of the project. Number of positions available: 1. Duration of the project: 3+ years.
Suggested reading:
- The nucleolus-like and precursor bodies of mammalian oocytes and embryos and their possible role in post-fertilization centromere remodelling. Biochem Soc Trans. 2020 Apr 29;48(2):581-593. doi: 10.1042/BST20190847.
- 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.