Opportunities

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Master thesis project: The role of the ion channels Piezo1 and TRPV4 in placental endothelial dysfunction in preeclampsia – tracking nitric oxide production

Department of Obstetrics and Gynaecology, Research Lab

Background: Preeclampsia (PE) is a hypertensive pregnancy disorder and a leading cause for maternal and perinatal death. Pathophysiologically, PE is thought to be evoked by impaired placental adaptation of the uterine blood vessels to pregnancy, which creates oxidative stress and placental dysfunction. It is known that placental arteries tend torwards a vasoconstrictive profile in PE [1] and PE placentas show increased vascular resistance [2], but the underlying mechanisms remain poorly understood limiting any treatment options.

Piezo1 is a mechanosensitive, Ca2+ permeable ion channel recently identified in the membrane of endothelial cells [3] where it is involved in important vascular functions such as mediating vasodilation via nitric oxide [4]. Furthermore, Piezo1 appears to act synergistically with another Ca2+ permeable ion channel, TRPV4, which has also been shown to be involved in nitric oxide production [5]. We hypothesise that both channels play an essential role in mediating placental vasodilation and that their function is impaired in PE.

Methods: Primary endothelial cells isolated from normal and preeclamptic placentae will be used to study nitric oxide production. Therefore, readily available nitric oxide probes (geNOps) [6] will be introduced into the cells by viral transfection. Once a reliable transfection protocol has been developed, channel functionality and nitric oxide production will be investigated by using chemical activators or blockers as well as shear stress as a more physiological trigger. Furthermore, the use of geNOps can be combined with concomitant imaging of the cytosolic Ca2+ levels to directly link channel opening to nitric oxide production.

Requirements: We are looking for a highly motivated candidate with a strong interest in basic medical research. The applicant should hold a Bachelor's degree in life science fields such as molecular biology, pharmacology or biochemistry/biotechnology. Experience with viral transfection is required. Since we are an international team, good English skills are expected.

What we offer:

 Being part of a highly motivated and curious international team of students&postdocs

 Supervision and guidance during experiments, data analysis and thesis writing

 Opportunity to expand your laboratory skills

 Working on a highly clinically relevant topic within the obstetrics department

 Publication of generated data as the work is embedded within a FWF-funded project [7]

 

Earliest starting date for the project is October 9 2023 - later start would be possible.

For further information or to submit your application please contact: Hanna Allerkamp, PhD

This email address is being protected from spambots. You need JavaScript enabled to view it.

Department of Obstetrics and Gynecology, Research Lab Medical University of Graz I

Phone: +43 316 385-17841

Additional information about the Placental lab at: https://placentalab.science/

 

References:

[1] E. Hitzerd et al., “Human placental vascular reactivity in health and disease: Implications for the treatment of pre-eclampsia,” Curr. Pharm. Des., vol. 25, no. 5, pp. 505–527, 2019. doi: 10.2174/1381612825666190405145228

[2] K. A. Eastwood, A. J. Hunter, C. C. Patterson, D. R. Mc Cance, I. S. Young, and V. A. Holmes, “Placental vascularization indices and prediction of pre-eclampsia in high-risk women,” Placenta, vol. 70, pp. 53–59, Oct. 2018, doi: 10.1016/j.placenta.2018.09.005.

[3] L. C. Morley et al., “Piezo1 channels are mechanosensors in human fetoplacental endothelial cells,” Mol. Hum. Reprod., vol. 24, no. 10, pp. 510–520, 2018, doi: 10.1093/molehr/gay033.

[4] Y. Li, J. Zheng, I. M. Bird, and R. R. Magness, “Mechanisms of shear stress-induced endothelial nitric-oxide synthase phosphorylation and expression in ovine fetoplacental artery endothelial cells.,” Biol. Reprod., vol. 70, no. 3, pp. 785–796, Mar. 2004, doi: 10.1095/biolreprod.103.022293.

[5] S. M. Swain and R. A. Liddle, “Piezo1 acts upstream of TRPV4 to induce pathological changes in endothelial cells due to shear stress.,” J. Biol. Chem., vol. 296, p. 100171, 2021, doi: 10.1074/jbc.RA120.015059.

[6] E. Eroglu et al., “Development of novel FP-based probes for live-cell imaging of nitric oxide dynamics,” Nat. Commun., vol. 7, 2016, doi: 10.1038/ncomms10623. 

[7] FWF Project Finder - Selection Mask

 

Ausschreibung Erasmus / Masterprojekt

Wir, die ForscherInnen des Perinatal Research Lab an der Frauenklinik der Meduni Graz bieten ein

Master Thesis Project

zum Thema Blutgefäßbildung in der humanen Plazenta. Die Plazenta ist ein faszinierendes Organ, das extra für die Schwangerschaft gebildet wird und parallel zum Baby wächst und sich entwickelt. Sie versorgt das Baby mit wichtigen Nährstoffen und Sauerstoff und ist dementsprechend reich in Blutgefäßen. Uns interessiert bei diesem Projekt, wie bestimmte Zelltypen in der Plazenta interagieren, um die Bildung der Blutgefäße voranzutreiben oder zu hemmen, und was das pathophysiologisch für eine gesunde Entwicklung des Kindes in der Schwangerschaft bedeutet. Dabei kommen unterschiedliche Methoden zum Einsatz, wir arbeiten mit Primärzellen, die wir selber aus der Plazenta isolieren, zum Teil auch mit Zelllinien. Neben Versuchen im Bereich Zellkultur verwenden wir auch klassische molekularbiologische Techniken wie RT-qPCR, Western Blot, ELISA, FACS. Auch histologische Färbungen und Untersuchungen sind Teil des Projekts. Die Dauer des Projekts sollte ungefähr 8 Monate betragen, kann aber auch flexibel vereinbart werden. Auch der Projektstart erfolgt gerne nach Vereinbarung, frühestens im September 2023. Idealerweise sollten Bewerber*Innen einen Hintergrund in Molekularbiologie/Biochemie/Medizinwissenschaften haben und etwas hands-on Erfahrung in Laborarbeit mitbringen. Eventuelle Fragen und Bewerbungen bitte an: This email address is being protected from spambots. You need JavaScript enabled to view it., Weitere Infos: www.placentalab.science (Homepage wird momentan aktualisiert)

 

We, the researchers of the Perinatal Research Lab at the Department of Gynecology of Meduni Graz offer an

Master Thesis Project

on the topic of blood vessel formation in the human placenta. The placenta is a fascinating organ that is formed specifically for pregnancy and grows and develops in parallel with the baby. It supplies the baby with important nutrients and oxygen and is accordingly rich in blood vessels. In this project, we are interested in how certain cell types in the placenta interact to drive or inhibit the formation of blood vessels, and what this means pathophysiologically for healthy development of the baby during pregnancy. Different methods are used; we work with primary cells that we isolate from the placenta ourselves, and in some cases also with cell lines. In addition to cell culture experiments, we also use classical molecular biology techniques such as RT-qPCR, Western blot, ELISA, FACS. Histological staining and examinations are also part of the project. The duration of the project should be approximately 8 months, but can be arranged flexibly. Also, the start of the project can be jointly agreed upon, earliest in September 2023. Ideally, applicants should have a background in molecular biology/biochemistry/medical sciences and some hands-on experience in laboratory work. Please send any questions and applications to: This email address is being protected from spambots. You need JavaScript enabled to view it., further information: www.placentalab.science (homepage is currently being updated).

 

 

MASTER THESIS PROJECT: Role of TGF-β signaling in placental macrophages – Hofbauer cells

MASTER THESIS PROJECT: Role of TGF-β signaling in placental macrophages – Hofbauer cells

Research Background: Hofbauer cells (HBCs) are resident macrophages of the feto-placental unit that regulate immune tolerance and tissue homeostasis (1). HBCs of the healthy placenta mainly exhibit an anti-inflammatory M2 phenotype and are primarily involved in phagocytosis of apoptotic cells, resolution of inflammation, tissue repair, and wound healing (2). Under exaggerated inflammatory conditions, such as preeclampsia (PE), a phenotypic switch to M1 polarization has been proposed. In macrophages, the TGF-β signaling pathway controls a variety of cellular processes and coordinates events that are critical for the progression and resolution of inflammatory responses. In the canonical signaling pathway, TGF-β binds to TGF-β receptors I - II (TGF-RI, TGFßRII), activating one of its major signal transducers, Smad3 (3). Smad3 is thought to play a role in maintaining the anti-inflammatory M2 phenotype. In addition, TGF-β is involved in the induction of M2 polarization and the regulation of MMP9 transcription and phagocytosis (4,5). The mechanisms and role of TGF-β signaling in Hofbauer cells are poorly understood. The aim of this study is to investigate the role of TGF-β/Smad3 signaling in primary HBCs under the inflammatory milieu of preeclampsia and its involvement in M1/M2 polarization and functionality of macrophages, such as phagocytosis and tissue remodeling.

Methods: Isolation of primary placental macrophages from preeclamptic and control placentas. To investigate subsequent signaling mechanisms, macrophages will be treated with selective inhibitors and ligands. Macrophage polarization will be determined using multicolor flow cytometry and molecular methods such as qPCR. In addition, analysis of the secretome will be performed. To investigate the signaling network, samples will be analyzed using qPCR, immunoblots, and phospho-flow cytometry. Student will perform the functional assays such as phagocytosis assay, apoptosis assay and gelatin zymography.

Requirements:

The applicant should be highly motivated and have an interest in basic medical research.

Furthermore, applicant should a Bachelor's degree in life science fields such as (molecular) biology, pharmacology and biochemistry/biotechnology.

Good English proficiency is required, since daily laboratory work is performed in English

What we offer:

 Opportunity to broaden technical laboratory skills

 Supervision and guidance during experiments, data analysis and thesis writing

 Working on a highly clinically relevant topic of placental research and processing of human samples

 Being part of highly motivated and curious international team of students/Postdocs

 Publication of generated data

For further information or to submit the application please contact:

Prof. Dr. Christian Wadsack - This email address is being protected from spambots. You need JavaScript enabled to view it.

Monika Horvat Mercnik MSc – This email address is being protected from spambots. You need JavaScript enabled to view it.

Department of Obstetrics and Gynecology Medical University of Graz

Phone: +43 316 385-17841 Additional

Project for Master Thesis

 

Interested and highly motivated students are encouraged to contact the PIs of the respective project.

Dissertation seminar

Cell culture techniques and isoltation of primary cells (PhD Molecular Medicine)

Lecturer (Assistant): Birgit Hirschmugl, Carolin Schliefsteiner, Alejandro Majali Martinez, Waltraud Brandl, Andrea Walcher, Monika Horvat

 

Content

- Common Trunk

  • Good scientific practice
  • General Molecular Biology
  • Cell Signalling/ Cell Cycle
  • Cell Culture
  • Cell Organelles
  • Lipid constituents of biological membranes & monolayers
  • Apoptosis
  • Immunology
  • Pharmacology

- Basic for Physicians