Junior Career Research Stipend
This 6-month stipend will be provided to support meritorious Masters or Medical Students over the period of their MSc / MD thesis, with interest particularly in pain research. The students will have the opportunity to work in an international scientific environment providing support for developing their career.
How to apply:
The interested candidate has to write a research proposal (maximally 2 pages) and may contact the PI of the project for additional information. The candidate can apply only for 1 project. The application material should include the proposal and CV (including grades from key exams, e.g. Abitur and Physikum for MD students). Please send the application material to
The deadline for applications is 15. September 2021.
Project overview:
Project 1 (Grinevich): How does oxytocin balance sociability and pain?
Project 2 (Tappe-Theodor): Endometriosis-associated pain
Project 3 (Üçeyler): Is it Fabry disease or an apathogenic polymorphism? Molecular analysis comparing two lines of patient-derived induced pluripotent stem cells (iPSC)
Project 4 (Mauceri): Functional characterization of novel mediators of spinal sensitization in chronic pain
Project 5 (Acuna Goycolea/Schrenk-Siemens/Mease): Linking pain channelopathies to single neuron computational phenotypes
Project 6 (Agarwal): Adrenergic signaling in glial cells – an unrecognized target in chronic pain
Project 7 (Ditzen): Social Influence on Pain Perception in Pelvic Pain and Endometriosis
Project 8 (Usai): The role of learning, stress and underlying brain circuits involving prefrontal-limbic interactions in the development of chronic back pain
Project 9 (T. Kuner): Multiscale correlational imaging of structural brain changes during chronic pain
Project 10 (Üçeyler): Dorsal root ganglion vascularization in Fabry disease
_____________________________________________________________________________________________________________________
Detailed descriptions:
Project 1 (Grinevich): How does oxytocin balance sociability and pain?
The hypothalamic neuropeptide oxytocin (OT) exerts not only prominent pro-social and anxiolytic effects, but has also garnered great attention for its analgesic actions. Recent studies demonstrated the existence of at least two OT sub-systems, which coherently mitigate the perception of physical pain and facilitate emotional coping with pain. In a recent study, we investigated the effects of OT on pain perception and anticipation within the insular cortex (IC), which integrates both pain processing and emotional valence. Our results indicate that OT signalling in the IC might improve emotional coping with pain, but that it is not involved in physical sensing of pain. Considering the strong pro-social properties of OT, we now aim to build on the basis of these findings and elucidate the social component of pain perception in regard to the interplay of the OT system and the IC. Therefore, we will utilise cell-type specific adeno-associated viruses (AAVs) in rats to disentangle axonal input from hypothalamic OT neurons to the IC, determine cell-types of the OTR neurons, and describe their output to the entire brain. Next, in an adapted behavioural social paradigm, we will investigate whether social contact affects the emotional valence towards induced pain after stimulated OT release in the IC. More specifically, to address this question, we will employ a chemogenetic approach to modulate the activity of OT neurons projecting to the IC in an operant box paradigm. Finally, and depending on the success of the preceding experiment, we will employ the established fiber photometry technique to determine whether social interaction will change the activity of IC OTR neurons in animals with inflammatory pain.
Methods:
Stereotactic surgeries on rats, perfusions, slicing of rat brains, immunohistochemistry, fluorescence microscopy, behavioural experiments, fiber photometry
Three key publications:
• Eliava, M., Melchior, M., Knobloch-Bollmann, H. S., Wahis, J., da Silva Gouveia, M., Tang, Y., ... & Grinevich, V. (2016). A new population of parvocellular oxytocin neurons controlling magnocellular neuron activity and inflammatory pain processing. Neuron, 89(6), 1291-1304.
• Boll, S., Almeida, de Minas A.C., Raftogianni, A., Herpertz, S.C., Grinevich, V. (2017) Oxytocin and pain perception: From animal models to human research. Neuroscience 2017 Sep 28. pii: S0306-4522(17)30694-2. doi: 10.1016/j.neuroscience.2017.09.041.
• Wahis, J., Baudon, A., Althammer, F., Kerspern, D., Goyon, S., Hagiwara, D., ... Grinevich, V. & Charlet, A. (2021). Astrocytes mediate the effect of oxytocin in the central amygdala on neuronal activity and affective states in rodents. Nature Neuroscience, 24(4), 529-541.
Contact details:
Prof. Dr. Valery Grinevich
Department of Neuropeptide Research in Psychiatry
Central Institute of Mental Health
University of Heidelberg
J 5 · 68159 Mannheim
Stephanie Küppers, PhD student
Department of Neuropeptide Research in Psychiatry
Central Institute of Mental Health
University of Heidelberg
J 5 · 68159 Mannheim
_____________________________________________________________________________________________________________________
Project 2 (Tappe-Theodor): Endometriosis-associated pain
Endometriosis is an inflammatory and estrogen-dependent disease that affects approximately 10 % of women of reproductive age and is characterized by debilitating chronic pelvic pain and infertility. It is defined by the presence of endometrial-like deposits outside the uterus (peritoneal, ovarian, and deep infiltrating lesions) resembling the uterine endometrium. The most widely accepted theory on the pathogenesis of endometriosis is the "retrograde menstruation" of endometrial tissue into the peritoneal cavity through the fallopian tubes. Intrinsic alterations in the endometrium, peritoneum, and patient's immune system may cause the development of initial endometriotic implants. The disease is accompanied by chronic inflammation with overproduction of prostaglandins, cytokines, chemokines, and increased activated macrophages in ectopic lesions. Current treatment strategies for endometriosis are restricted to surgical excision of the lesions or suppression of ovarian function with hormonal intervention associated with high recurrence rates and several side effects. Promising anti-inflammatory and anti-angiogenic agents have also been tested in preclinical and clinical studies, but none have been introduced in clinical practice. Effective analgesics for the treatment of pain associated with endometriosis are also lacking. Most of the research regarding endometriosis has focused on the pathogenesis of endometriosis lesions rather than pain mechanisms. The fact that surgical removal of lesions alleviates pain in some patients indicates that lesions contribute to pain. However, pain can often return after surgery without evidence of new lesions, and, importantly, the severity of pain symptoms does not correlate with the extent of lesions.
Methods:
We will use a mouse model of endometriosis consisting of the injection of decidualized endometrial tissue from donor mice into the peritoneum of recipient mice, leading to the development of lesions similar to that observed in patients. We will characterize the pain-related behavior in this model using a portfolio of stimulus-evoked and voluntary behavioral paradigms. Additionally, we will study the identity of the sensory fibers innervating the lesions and their functional role in mediating endometriosis-associated pain using immunohistochemical methods.
Project-related publications
• Vanhie A, Tomassetti C, Peeraer K, Meuleman C, and D'Hooghe T. Challenges in the development of novel therapeutic strategies for treatment of endometriosis. Expert Opin. Ther. Targets. 2016; 20(5):593–600.
• Simitsidellis, Gibson, and Saunders. Animal models of endometriosis: Replicating the aetiology and symptoms of the human disorder. Best Pract. Res. Clin. Endocrinol. Metab. 2018; 32(3):257–269.
• Greaves E, Horne AW, Jerina H, Mikolajczak M, Hilferty L., Mitchell R, Fleetwood-Walker SM, and Saunders PTK. EP2 receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis. Sci. Rep. 2017; 7:1–10.
Key publications of the PI
• Pitzer C, Kuner R, Tappe-Theodor A. Voluntary and evoked behavioral correlates in neuropathic pain states under different housing conditions. Mol Pain. 2016; 15;12.
• Tappe-Theodor A, King T, Morgan MM. Pros and Cons of Clinically Relevant Methods to Assess Pain in Rodents. Neurosci Biobehav Rev. 2019;100:335-343.
• La Porta C, Tappe-Theodor A. Differential impact of psychological and psychophysical stress on low back pain in mice. Pain. 2020;161(7):1442-1458.
Contact details:
PD Dr. Anke Tappe-Theodor
Pharmacology Institute
University of Heidelberg
Im Neuenheimer Feld 366
69120 Heidelberg
_____________________________________________________________________________________________________________________
Project 3 (Üçeyler): Is it Fabry disease or an apathogenic polymorphism? Molecular analysis comparing two lines of patient-derived induced pluripotent stem cells (iPSC)
Aim:
Investigating the impact of two genetic variants highly discussed as pathogenic versus apathogenic in Fabry disease (FD).
Background:
Fabry disease is an X-linked lysosomal storage disorder, which is caused by various mutations in the gene encoding alpha-galactosidase A. Depending on the type and location of the genetic variant, symptoms and disease severity are very heterogeneous. Mutations may lead to a classic Fabry phenotype or may be associated with symptoms not typical for Fabry disease. Distinguishing these variants in clinical practice is crucial when deciding on initiating Fabry-specific treatment. Two such variants of uncertain pathogenicity, D313Y and A143T, will be investigated in patient-derived iPSC and iPSC-derived endothelial cells.
Tasks:
• Generation of two iPSC-lines, D313Y and A143T, via mRNA transfection of patient derived dermal fibroblasts
• Cultivation and differentiation of iPSC into endothelial cells
• Investigation of globotriaosylceramide accumulations and enzyme activity in endothelial cells compared to healthy control lines and cell lines of patients with classic Fabry mutations
Techniques:
Cell culture, mRNA transfection, enzyme activity assay, immunocytochemistry, microscopy
Publications:
• Oder D, Üçeyler N, Liu D, Hu K, Petritsch B, Sommer C, Ertl G, Wanner C, Nordbeck P. Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y. BMJ Open. 2016 Apr 8;6(4):e010422. doi: 10.1136/bmjopen-2015-010422. PMID: 27059467
• Klein T, Günther K, Kwok CK, Edenhofer F, Üçeyler N. Generation of the human induced pluripotent stem cell line (UKWNLi001-A) from skin fibroblasts of a woman with Fabry disease carrying the X-chromosomal heterozygous c.708 G > C (W236C) missense mutation in exon 5 of the alphagalactosidase-A gene. Stem Cell Res. 2018 Aug;31:222-226. doi: 10.1016/j.scr.2018.08.009. Epub 2018 Aug 10. PMID: 30130681.
• Lenders M, Weidemann F, Kurschat C, Canaan-Kühl S, Duning T, Stypmann J, Schmitz B, Reiermann S, Krämer J, Blaschke D, Wanner C, Brand SM, Brand E. Alpha-Galactosidase A p.A143T, a non-Fabry disease-causing variant. Orphanet J Rare Dis. 2016 May 4;11(1):54. doi: 10.1186/s13023-016-0441-z. PMID: 27142856; PMCID: PMC4855861.
Contact:
Application documents (CV and motivation letter) to Prof. Dr. N. Üçeyler:
_____________________________________________________________________________________________________________________
Project 4 (Mauceri): Functional characterization of novel mediators of spinal sensitization in chronic pain
The group of Dr. Daniela Mauceri (Neurobiology, IZN) is looking for an exceptionally motivated, skilled, student for a Master Thesis, "Functional characterization of novel mediators of spinal sensitization in chronic pain".
Pain is essential for our well-being. Chronic pain, on the other hand, is a debilitating condition affecting a significant percentage of the worldwide population. Central sensitization, typical of chronic pain, is sustained by plasticity and gene transcription-dependent maladaptive changes in the CNS. The following project offers the possibility to investigate the functional role and expression of newly identified epigenetically-regulated mediators of chronic pain. Using transgenic mice lines, as well as a variety of molecular and pharmacological tools, the project will characterize the expression of our genes of interest in different chronic pain models and then proceed to assess its impact on development and maintenance of chronic pain.
Methods that will be used:
|
• Animal models of pain (mouse) |
• ICC/IHC • Microscopy • In vitro primary neuronal culture • Cell Biology |
The successful applicant has a good background and interest in neurobiology. S/He has very good technical skills in basic laboratory techniques and is highly motivated to work efficiently in an independent manner in our group. The project require the use of mouse models of pain, applicants with FELASA certificate will have an advantage. Extensive practical lab training is intended to precede the beginning of the master project.
Literature:
• Oliveira AM, Litke C, Paldy E, Hagenston AM, Lu J, Kuner R, Bading H, Mauceri D. Epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo DNA methyltransferase Dnmt3a2. Mol Pain. 2019 15:1744806919827469.
• Litke C, Bading H, Mauceri D. Histone deacetylase 4 shapes neuronal morphology via a mechanism involving regulation of expression of vascular endothelial growth factor D. J Biol Chem. 2018 293(21):8196-8207.
• Simonetti M*, Hagenston AM*, Vardeh D*, Freitag HE*, Mauceri D*, Lu J, Satagopam VP, Schneider R, Costigan M, Bading H, Kuner R. Nuclear calcium signaling in spinal neurons drives a genomic program required for persistent inflammatory pain. Neuron. 2013 77(1):43-57. *equal contribution
Contact:
Dr. Daniela Mauceri (Neurobiology, IZN)
_____________________________________________________________________________________________________________________
Project 5 (Acuna Goycolea/Schrenk-Siemens/Mease): Linking pain channelopathies to single neuron computational phenotypes
We seek an enthusiastic MD or MS student for an exciting project at the interface of stem-cell biology, pain research, and computational neuroscience. This project aims to assess how pain-related mutations in voltage-gated ion channels give rise to altered excitability phenotypes at the levels of single neurons and small networks.
The specific focus is pathogenic mutations in Nav1.7 channels, which cause inherited erythromelalgia (IEM), a severe pain syndrome characterized by episodes of intense burning pain triggered by warmth. It is largely unknown how IEM-linked Nav1.7 mutations impact information processing at peripheral-to-central synapses, a crucial node in pain pathophysiology. Here, we plan to re-constitute pluripotent cell-derived human peripheral-to-central synapses carrying IEM-linked Nav1.7 mutations and record the activity of these rudimentary networks using patch clamp electrophysiology. We will further characterize the impact of such mutations on single-neuron encoding properties by fitting statistical models to experimental data collected from control and mutant neurons and synapses.
The project concretely aims to:
1) Assess and model changes in single-neuron excitability in peripheral and central neurons carrying IEM-linked Nav1.7 mutations.
2) Assess further the impact of IEM-linked Nav1.7 mutations on synaptic transmission and plasticity mechanisms at peripheral-to-central synapses.
3) Assess pathological network dynamics arising from intrinsic and synaptic effects of IEM-linked Nav1.7 mutations.
This project offers experience in diverse experimental and analytical methods: stem-cell technologies, in vitro single-cell electrophysiology, mathematical modeling, and information theory. There are two possible courses of study, depending on the applicant’s background:
1) Experimental: students from medical or biological backgrounds would develop and validate pain models based on Nav1.7 mutations and do whole-cell patch-clamp electrophysiology to assess neuron excitability and synaptic function.
2) Computational: students from a quantitative background would use statistical and mechanistic modeling and information theoretic techniques to characterize and predict how IEM-linked Nav1.7 mutations change single neuron coding properties.
References:
• R.A. Mease, T. Kuner, A.L. Fairhall, A. Groh. (2017). Multiplexed spike coding and adaptation in the thalamus. Cell Reports. https://pubmed.ncbi.nlm.nih.gov/28494863/
• Schrenk-Siemens K, Pohle J, Rostock C, Abd El Hay M, Lam RM, Szczot M, Lu S, Chesler AT, Siemens J (2020) HESC-derived sensory neurons reveal an unexpected role for PIEZO2 in nociceptor mechanotransduction. bioRxiv 741660. https://www.biorxiv.org/content/10.1101/741660v1
• Zhang Y, Pak C, Han Y, Ahlenius H, Zhang Z, Chanda S, Marro S, Patzke C, Acuna C, Covy J, Xu W, Yang N, Danko T, Chen L, Wernig M, Südhof TC (2013) Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron. 78(5):785-98. https://pubmed.ncbi.nlm.nih.gov/23764284/
Goodwin G and McMahon S (2021). The physiological function of different voltage-gated sodium channels in pain. Nat Rev Neurosci. 22(5):263-274. https://pubmed.ncbi.nlm.nih.gov/33782571/
Contact:
Before submitting the application, applicants should contact the PIs directly:
Dr. Katrin Schrenk-Siemens ()
Institute of Pharmacology, Heidelberg University
Dr. Claudio Acuna Goycolea ()
Chica and Heinz Schaller Foundation, Heidelberg University
Dr. Rebecca Mease ()
Institute of Physiology and Pathophysiology, Heidelberg University
_____________________________________________________________________________________________________________________
Project 6 (Agarwal): Adrenergic signaling in glial cells – an unrecognized target in chronic pain
We are looking for a highly enthusiastic student for performing an experimental masters (in Biosciences, MSc) or medical doctoral (MD) thesis project in optical neurophysiology and behavioral neurosciences. In this project we aim to study how glia cells, constituting half of our brain cells, modulate chronic pain.
It is well known that activation of locus coeruleus (LC) in the brain modulate chronic pain. Although LC is a very small nucleus located in the brainstem, it can modulate activity of a large part of the brain through noradrenergic neurotransmission mediated by volumetric release of noradrenaline (NE). Astrocytes, one of the major glial cell-type in the brain and spinal cord, express adrenergic receptors and respond to NE release. Recent studies indicate astrocytes might play a central role in the development and maintenance of hyperalgesia and allodynia. However, little is known about how NE signaling in astrocyte can participate in pain regulation.
In this project the candidate will use a diverse range of advanced technologies, such as long-term glass cranial-window based multiphoton imaging, chemogenetics, AAV based viral vectors, electrophysiology, generation mouse model of chronic pain (spared nerve injury model) and mouse pain-behavioral analysis, to tackle following aims:
1) Study how short- and long-term chemogenetic activation or inhibition of LC in can modulate chronic pain
2) Study how direct chemogenetic activation astrocytes can modulate chronic pain
3) Optophysiological analysis of neuron-glia cross-talk in pain chronification
Key publications:
• Agarwal A et al. Transient Opening of the Mitochondrial Permeability Transition Pore Induces Microdomain Calcium Transients in Astrocyte Processes. Neuron 93 (3), 587-605.
• Paukert M, Agarwal A, et al. Norepinephrine Controls Astroglial Responsiveness to Local Circuit Activity. Neuron 82 (6), 1263-1270.
• Poe GR, Foote S, Eschenko O, Johansen JP, Bouret S, Aston-Jones G, Harley CW, Manahan-Vaughan D, Weinshenker D, Valentino R, Berridge C, Chandler DJ, Waterhouse B, Sara SJ. Locus coeruleus: a new look at the blue spot. Nat Rev Neurosci. 2020 Nov;21(11).
• Ji, R. R., Berta, T., & Nedergaard, M. (2013). Glia and pain: is chronic pain a gliopathy?. Pain, 154 Suppl 1(0 1), S10–S28. https://doi.org/10.1016/j.pain.2013.06.022
Contact:
Dr. Amit Agarwal
Institute of Anatomy and Cell Biology, Heidelberg University
_____________________________________________________________________________________________________________________
Project 7 (Ditzen): Social Influence on Pain Perception in Pelvic Pain and Endometriosis
This project assesses the influence of social interactions and stress on pain perception in patients with chronic pelvic pain and endometriosis. It is possible to write your thesis in one of several fields:
a) In an ecological momentary assessment (EMA) study, we will measure the perception of social support, stress, and pain in patients and their partners. These measures will be correlated with endogenous cortisol and oxytocin levels.
b) In an fMRI study we will conduct a stress and pain paradigm and assess how neural activity differs between patients and healthy controls.
c) Endometrial tissues will be examined in order to find differences in the expression of genes and proteins. The results will be related to pain levels (in cooperation with Prof. Germeyer and her team at the University’s Women’s Hospital Heidelberg).
The project is designed to identify upholding mechanisms in chronic pain and to develop reliable diagnostics and therapies for endometriosis and chronic pelvic pain.
Used Methods:
• ecological momentary assessment (EMA)
• functional magnetic resonance imaging (fMRI)
• online questionnaires
• PCR gene analyses of endometrial tissue
Key publications:
• Holzer, I., Machado Weber, A., Marshall, A., Freis, A., Jauckus, J., Strowitzki, T., & Germeyer, A. (2020). GRN, NOTCH3, FN1, and PINK1 expression in eutopic endometrium – potential biomarkers in the detection of endometriosis – a pilot study. Journal Of Assisted Reproduction And Genetics, 37(11), 2723-2732. doi: 10.1007/s10815-020-01905-4.
• van Stein, K. R., Schubert, K., Weise, C. & Ditzen, B. (manuscript in preparation). Psychobiosocial Aspects of Endometriosis. A Research Domain Criteria Approach.
• Zeltner, N. A., Ehlert, U. & Ditzen, B. (2014). Psychische Beschwerden im Rahmen gynäkologischer Erkrankungen am Beispiel der Endometriose. Verhaltenstherapie und Verhaltensmedizin, 34(4), 483-502.
If you have further questions or want to apply for funding please get in touch with:
Dr. Monika Eckstein ()
06221-56-7871
_____________________________________________________________________________________________________________________
Project 8 (Usai): The role of learning, stress and underlying brain circuits involving prefrontal-limbic interactions in the development of chronic back pain
We seek to determine the behavioral and neural mechanisms related to the role of social learning and social interactions with the significant other and their impact on the maintenance and the potential pain-increasing role of positive reinforcement of chronic back pain.
A hyperscanning approach (Koike et al., 2015, Wager et al. 2013) during simultaneous functional magnetic resonance imaging (fMRI) of both patient and their significant other will be used. Two consecutive runs will be performed, in which painful thermal stimulations are applied to the upper back of the patient while either both partners can see each other via video cameras or without visual feedback of the respective partner. In each run the patient will receive 20 painful thermal stimulations and will evaluate the stimulation intensity and pain unpleasantness after each trial. While the spouse will not receive any stimulation his-/herself, but will always see the behavioral ratings and a live video of the patient presented at the center of the screen. In addition, a behavioral task including real-life movements will be used to track pain behaviors of our patients in presence/absence of their spouse. Furthermore, we will employ ecological momentary assessments (EMA) to track daily life interactions between patients and their significant others.
This approach allows us to test whether the presence/absence of the spouse affects the behavioral and the neural circuits during painful stimulation in the pain patient (Flor et al., 1989). We will classify solicitous and non-solicitous relationships and compare brain activation patterns and behavioral responses across these groups, to investigate whether the significant other impacts the maintenance of the pain problem. Thereby, we are able to directly correlate the patients’ pain behaviors to the potential pain-increasing role of positive reinforcement tested during hyperscanning, with social support modulating both behavior and neural mechanisms.
So far, studies investigating the role of social interactions in the context of chronic back pain are sparse. Aim of this project is to identify whether significant others can contribute to the maintenance of the pain problem via social reinforcement.
The applicant’s tasks will include all experimental acquisitions and the supervision of the EMA assessments.
For further details please contact:
Dr. Katrin Usai
Department of Cognitive and Clinical Neuroscience
Central Institute of Mental Health
_____________________________________________________________________________________________________________________
Project 9 (T. Kuner): Multiscale correlational imaging of structural brain changes during chronic pain
Project description:
Magnetic resonance imaging (MRI) studies have shown that chronic pain is accompanied by altered brain grey matter volume (GMV) in humans and rodent models. The physical and cellular underpinnings of these structural changes and their causal relationship to chronic pain remain elusive, yet are important to understand in order to develop new treatment strategies.
The aim of the thesis will be to define cellular correlates for the GMV changes in chronic pain in a correlative imaging study with mice.
Methods:
Two-photon intravital imaging, rodent models for neuropathic pain (Spared Nerve Injury) and other pain types, behavioral testing, small animal MRI (in cooperation with ZI Mannheim, AG Weber-Fahr), participation in the development of a machine learning-based workflow for automatic analysis of the image data.
Related publications:
• Asan, L., Falfán-Melgoza, C., Beretta, C.A., Sack, M., Zheng, L., Weber-Fahr, W., Kuner, T., and Knabbe, J. (2021). Cellular correlates of gray matter volume changes in magnetic resonance morphometry identified by two-photon microscopy. Scientific Reports 11, 4234.
• Kuner, R., and Kuner, T. (2020). Cellular circuits in the brain and their modulation in acute and chronic pain. Physiol Rev.
• Tan, L.L., Pelzer, P., Heinl, C., Tang, W., Gangadharan, V., Flor, H., Sprengel, R., Kuner, T., and Kuner, R. (2017). A pathway from midcingulate cortex to posterior insula gates nociceptive hypersensitivity. Nat Neurosci 20, 1591–1601.
Applicants are requested to send a CV and a short motivation letter to:
Prof. Dr. Thomas Kuner
Department of Functional Neuroanatomy, Heidelberg University
.
Any questions about the project or relating issues may be directed to the same address.
_____________________________________________________________________________________________________________________
Project 10 (Üçeyler): Dorsal root ganglion vascularization in Fabry disease
Aim:
Investigation of blood vessel density in dorsal root ganglia (DRG) of a mouse model of Fabry disease.
Background:
Our lab is investigating the rare lysosomal storage disorder Fabry disease. Patients are often suffering from episodic acral burning pain which is triggerable by heat, fever, and physical activity. The underlying pathomechanism is yet not fully understood. Publications and preliminary data suggest malperfusion of patients‘ DRG which are the first organs involved in pain processing. Such malperfusion may lead to a hypoxic state in DRG neurons. This can lead to a cascade of cellular reactions including inflammatory responses and pain. We aim at investigating the morphology of blood vessels within DRG of a Fabry mouse model, the alpha-galactosidase-A-deficient mouse (GLA KO). We will use DRG of GLA KO and wildtype mice for tissue clearing and compare the two groups histologically for their blood vessel morphology.
Tasks:
• Dissection and histological preparation of DRG
• Establishment of suitable clearing and staining protocols for DRG blood vessel visualization
• Microscopic analysis of DRG blood vessels
• Statistical analysis
Techniques:
• DRG dissection, preparation of DRG cryosections, immunofluorescent staining, immunohistochemistry, tissue clearing, microscopy (fluorescence and bright field), graphical and statistical data analysis
Publications:
• Hofmann L, Hose D, Grießhammer A, Blum R, Döring F, Dib-Hajj S, Waxman S, Sommer C, Wischmeyer E, Üçeyler N. Characterization of small fiber pathology in a mouse model of Fabry disease. Elife. 2018 Oct 17;7:e39300. doi: 10.7554/eLife.39300.
• Üçeyler N, Biko L, Hose D, Hofmann L, Sommer C. Comprehensive and differential long-term characterization of the alpha-galactosidase A deficient mouse model of Fabry disease focusing on the sensory system and pain development. Mol Pain. 2016 May 4;12:1744806916646379.
Contact:
Application documents (CV and motivation letter) to:
_____________________________________________________________________________________________________________________