Thesis topics

Specific PhD projects

Ageing research

• Adipose stem cells in obesity and caloric restriction (ASC)
• Mitochondria in ageing (MIA)
• Plant ageing (PA)
  

Regeneration and stem cell research

• Stemness and ageing in tunicates (SAT)
• Stem cells and regeneration (SCR)
• cWnt-Myc signaling in stem cell decision making and regeneration (WSR)
• Neural stem cells and neurodevelopmental disorders (NDD)

Drug discovery and development

• Biology of voltage-gated calcium-channels (BVC)
• Total synthesis of polycyclic anti-ageing natural products (TAP)
• Metabolic signaling drives ageing: the interplay of the mTOR kinase network with energy metabolism and neuronal function (MSA) 
• Natural compounds in ageing and regeneration (NAR)
• Molecular modelling in ageing and regeneration (MAR)
  

Adipose stem cells in obesity and caloric restriction (ASC)

The Zwerschke lab  works on adipose tissue biology with main emphasis on molecular mechanisms underlying proliferation, differentiation and aging of adipose stem/progenitor cells (ASCs). In addition, the group studies the impact of obesity and weight-loss interventions (such as caloric restriction) on ASCs and analyses the effects of weight-loss mimetics on ASCs and adipocytes. To address our research questions, we use genomics, transcriptomics and proteomics technologies, modern techniques of molecular and cell biology including CRISPR-mediated genome editing, flow cytometry and up-to-date imaging technologies. We work with primary human cells ex vivo and in cell culture and use genetic animal models.

Thesis topic 1: Role of weight-loss target genes in adipose stem/progenitor cells (ASC-1)

In this project we will use cell culture and modern techniques of molecular and cell biology to analyze the role of weight-loss target genes in human adipose stem/progenitor cells.

Supervisor: Zwerschke; Co-supervisor: Thedieck/Rothbächer

Theses topic 2: Establishment of a mouse model to study effects of caloric restriction / weight loss interventions on adipose tissue (ASC-2)

In this project we will use a mouse model and cell culture techniques to study the impact of caloric restriction / weight-loss interventions on adipose tissues.

Supervisor: Zwerschke; Co-supervisor: Jansen-Dürr 

Biology of voltage-gated calcium-channels (BVC)

Voltage-gated Ca2+-channels regulate the influx of Ca2+-ions into electrically excitable cells in response to changes in membrane potential. The resulting intracellular Ca2+-transients are essential for key physiological processes including muscle contraction, hormone secretion, sensory functions, neurotransmitter release, neuronal plasticity in neurons as well as learning and memory.

Our interdisciplinary team uses a wide spectrum of advanced biophysical, biochemical, molecular and cell biological, techniques to characterize the consequences of Ca2+-channel dysfunction in vitro and in vivo for several human disease. This includes neurological diseases (such as seizures) and neurodevelopmental disorders, including autism spectrum disorder.

Thesis topic 1: The role of L-type Ca2+ channels for brain ageing and neuropsychiatric disorders (BVC-1)

In this project we will use electrophysiological (brain slice recordings), immunohistochemical and biochemical techniques (e.g. qPCR, Western blotting) and perform behavioral studies in mice to study alterations in brain function induced by human Ca2+ channel mutations causing neuropsychiatric disorders and also determine effects on aging.

Supervisor: Striessnig; Co-supervisor: Edenhofer/Hobmayer

Thesis topic 2: Subtype-selective inhibition of voltage-gated calcium channels (BVC-2)

In this project we will use a combination of molecular modeling and electrophysiological techniques (Ca2+ channel recordings in wildtype and mutant Ca2+ channels) to characterize existing and discover new subtype-selective Ca2+ channel blockers.

Supervisor: Striessnig; Co-supervisor: Liedl/Edenhofer

Total synthesis of polycyclic anti-ageing natural products (TAP) 

Natural products are a fundamental source for novel bioactive agents. However, the complex architecture of these molecules often prevents their application in medicinal chemistry. For the Magauer Lab, this is an inspiration to think about innovative retrosynthetic bond disconnections which enable rapid access to the target compounds. We develop powerful transformations such as cationic cyclizations and ring-expansions and apply them to the total synthesis of biologically relevant complex natural products and simplified analogs thereof. The goal of these projects is to shed light on proposed biosynthetic processes, to identify new molecular targets and ultimately provide new drugs.

Thesis topic 1: Natural products for regulation of mitochondrial function (TAP-1)

In this project we will realize the chemical synthesis of complex molecules using modern synthetic methods. Characterization and structure elucidation will be performed via (2D)-NMR, X-ray analysis and HRMS.

Supervisor: Magauer; Co-supervisor: Stuppner/Jansen-Dürr

Thesis topic 2: Chemical synthesis of anti-ageing natural products (TAP-2)

In this project we will realize the chemical synthesis of complex molecules using modern synthetic methods. Characterization and structure elucidation will be performed via (2D)-NMR, X-ray analysis and HRMS.

Supervisor: Magauer; Co-supervisor: Stuppner/Liedl

cWnt-Myc signaling in stem cell decision making and regeneration (WSR)

The Hobmayer lab studies adult stem cells and their action in regeneration and ageing phenomena in the simple multicellular animal Hydra. Hydra represents a classic model system showing unparalleled capacity for regeneration, dynamic adult stem cell lineages, and an extensive life span. We analyze the roles of Wnt signaling pathways and oncogenic Myc transcription factors, two core regulators in adult stem cell decision making. By using state-of-the-art light and electron microscopic approaches in combination with methods of genetic interference, we try to understand our research topics at cellular and molecular levels.

Thesis topic 1: Role of mitochondria in inducible ageing phenotypes in hydra (WSR-1)

In this project we will apply methods of gene expression, pharmacological and genetic interference, genetic transformation, and transmission electron microscopy.

Supervisor: Hobmayer; Co-supervisor: Jansen-Dürr/Kranner

Thesis topic 2: Role of nuclear beta-Catenin in lineage determination of stem cells in hydra (WSR-2)

In this project we will apply methods of cell cycle analysis, gene expression, genetic interference and gene editing, and single cell transcriptomics.

Supervisor: Hobmayer; Co-supervisor: Rothbächer/Edenhofer

References:

Hartl, M., Glasauer, S., Gufler, S., Raffeiner, A., Puglisi, K., Breuker, K., Bister, K., and Hobmayer, B. (2019) Differential regulation of myc homologs by Wnt/β-Catenin signaling in the early metazoan Hydra. FEBS J. 286, 2095-2310.

Gufler, S., Artes, B., Bielen, H., Krainer, I., Eder, M.-K., Falschlunger, J., Bollmann, A., Ostermann, T., Valovka, T., Hartl, M., Bister, K., Technau, U., and Hobmayer, B. (2018) β-Catenin acts in a position-independent regeneration response in the simple eumetazoan Hydra. Dev. Biol. 433, 310-323.

Metabolic signaling drives ageing: the interplay of the mTOR kinase network with energy metabolism and neuronal function (MSA)

The Lab for Metabolic Signaling studies the control of metabolic homeostasis by kinase networks centred on the mammalian/mechanistic target of rapamycin (mTOR). Located at the insitute of biochemistry (faculty of chemistry and pharmacy), we adopt biochemistry, cell biology, proteomics, metabolomics and systems modelling approaches. Our institute hosts own mass spectrometry and microscopy units, enabling high resolution proteomics, metabolomics, and imaging.

Thesis topic 1: The interplay of kinase signalling with mitochondrial metabolism (MSA-1)

We will take advantage of our combined expertise in analyzing mTOR signaling and cellular metabolism (Thedieck lab) and mitochondrial metabolism and function (Jansen-Duerr lab) to unravel the mechanisms underlying (i) mTOR’s effects on mitochondrial function and (ii) mitochondrial effects on mTOR network activity. Particular emphasis will be on modeling and experimentally testing the effects of drugs targeting mTOR or other components of the mTOR network, and their combinatorial use with compounds targeting ROS-redox metabolism.

Supervisor: Thedieck; Co-supervisor: Jansen-Dürr

Thesis topic 2: mTORC1 in the control of lipid metabolism and neuronal stemcellness (MSA-2)

We will take advantage of our combined expertise in mTOR signaling and metabolism (Thedieck lab), lipid metabolism (Zwerschke lab), and neuronal differentiation and function (Edenhofer lab). We will investigate the role of known and novel GTPases upstream of mTOR in lipid metabolism. We will study their effects on mTOR and mTOR-driven metabolism in the context of tumor cell proliferation and neuronal function in the model organism C. elegans as well as in human cell culture. In particular, we will focus on neuronal progenitors and neuronal cells, derived from hiPSCs.

Supervisor: Thedieck; Co-supervisors: Zwerschke / Edenhofer

Mitochondria in ageing (MIA)

The Jansen-Dürr lab investigates the role of mitochondria in cellular senescence and ageing. Besides the role of mitochondrial quality control in ageing of the human skin and other tissues, our work focuses on the in vivo function of FAHD1, a newly identified human mitochondrial enzyme with oxaloacetate decarboxylase activitiy. To address these research questions, we use multiple -omics technologies, molecular genetics, as well as state-of-the-art imaging technologies in cell culture models, reconstructed human skin and FAHD1 loss-of-function animal models.

Thesis topic 1: Role of mitochondrial quality control in skin ageing (MIA-1)

In this project we will use 2D and 3D cell culture models to analyze the role of mitochondrial quality control in skin aging caused by environmental factors (UV, air pollutants).

Supervisor: Jansen-Dürr; Co-supervisor: Thedieck

Thesis topic 2: FAHD1 inhibitors in ageing and cancer research (MIA-2)

In this project we will use animal and cell culture models to investigate the role of oxaloacetate decarboxylase FAHD1 in ageing and tumor biology, using genetic and small molecule modulators of FAHD1 activity.

Supervisor: Jansen-Dürr; Co-supervisor: Liedl

Molecular modelling in ageing and regneration (MAR)

Klaus Liedl and his research group focus on the development and application of computational methods to rationalize and predict chemical and biochemical phenomena at a molecular level. This comprises scientific areas such as molecular dynamics simulations, quantum mechanical calculations and chemo- and bioinformatics. The group both develops molecular force fields and data analysis methods and applies existing methods to explain experimental results and to guide future experiments.

Thesis topic 1: From hit to lead and beyond: In silico optimisation of FAHD1 inhibitors (MAR-1)

Based on structural information and inhibition assay data the successful applicant will improve the binding affinity of chemical scaffolds to FAHD1 in close collaboration with synthetic chemistry and molecular biology. The binding thermodynamics and kinetics will be analyzed by computer simulations and experimental techniques like ITC and SPR.

Supervisor: Liedl; Co-supervisor: Jansen-Dürr/Magauer

Thesis topic 2: Phenotype prediction of calcium channel-related diseases (MAR-2)

In this project we will predict the phenotype of mutations based on public databases containing a large number of single nucleotide polymorphisms (SNPs) for genes coding calcium channels. Some of these mutations are already experimentally characterized and result in diseases whereas others are benign. A large group of mutations, instead, is still not characterized concerning their phenotype. Assays will be prioritized by the prediction of  structural changes caused by these mutations.

Supervisor: Liedl; Co-supervisor: Striessnig

Natural compounds in ageing and regeneration (NAR) 

The Department of Pharmacognosy has its competence in natural products research, including the isolation and structural elucidation of novel compounds, their analysis in biological matrices and commercial products by state-of-the-art techniques, as well as activity evaluations in-vitro and in-silico. For the discovery of new (bioactive) natural products different strategies are followed e.g. the investigation of new or poorly studied biological sources, or screening of extracts (mostly with ethno-pharmacological background) followed by dereplication and bioactivity-guided isolation.

Thesis topic 1: Secondary lichen products and their potential medicinal properties (NAR-1)

In this project we will be trained in modern analytical and preparative techniques as well as spectroscopic and spectrometric methods like (U)HPLC-MS and NMR.

Supervisor: Stuppner; Co-supervisor: Kranner/Magauer

Thesis topic 2: Novel natural compounds - derived scaffolds inhibiting voltage-gated calcium channels (NAR-2)

In this project we will use modern analytical and preparative techniques as well as spectroscopic and spectrometric methods to identify active natural products.

Supervisor: Stuppner; Co-supervisor: Striessnig/Liedl

Neural stem cells and neurodevelopmental disorders (NDD)

The Edenhofer lab analyses the core transcriptional network regulating pluripotency and neural stemness including Oct-4, Nanog, Sox2, Brn-2 and Myc. The group developed a strategy to directly convert human skin-derived fibroblasts to induced neural stem cells (iNSCs). iNSCs are being validated for disease modeling and cell therapy approaches focusing at myelin deficiency, Multiple Sclerosis, and neurodevelopmental disorders (NDD). We apply human (neural) stem cell culture, targeted neural differentiation in 2D, derivation of complex 3D neural tissue organoids, histology, immunohistochemistry, confocal microscopy; moreover, we use genome-wide omics approaches to understand organ function at a global level. Our findings will help to develop reliable models of CNS function and dysfunction and provide a novel cellular basis for autologous cell replacement therapy.

Thesis topic 1: Calcium channel mutations causing neurodevelopmental disorders - Role of Cav1.3 gain of function channel mutations for neuronal cell survival and ageing (NDD-1)

Supervisor: Edenhofer; Co-supervisor: Striessnig

Thesis topic 2: Impact of human-specific instructors on neural stem cell self renewal and development of neuronal diversity (NDD-2)

Supervisor: Edenhofer; Co-supervisor: Thedieck/Hobmayer

Plant ageing (PA)

Thesis topic 1: Ageing in the plant Arabidopsis thaliana and potential roles of FAHD1 homologues (PA-1)

In this project we will use hyphenated techniques such as HPLC, LC-MS/MS (targeted analyses of plant metabolites including plant hormones) and GC-MS/MS (metabolomics), enzymology and molecular characterization of plant genotypes

Supervisor: Kranner; Co-supervisor: Jansen-Dürr

Thesis topic 2: Redox homeostasis and signalling during plant and seed ageing (PA-2)

In this project we will use hyphenated techniques such as HPLC, LC-MS/MS (targeted analyses of plant metabolites including plant hormones) and GC-MS/MS (metabolomics), EPR and spectrophotometrical methods to study redox regulation of plants

Supervisor: Kranner; Co-supervisor: Stuppner

Stem cells and regeneration (SCR)

The Meyer lab investigates pancreatic fate determination during development and organ-regeneration. Main focus of our work is on the formation and function of insulin secreting beta-cells and on genetic conditions of diabetes. In our research we use genetic and high-resolution live imaging approaches in zebrafish and human cell culture models to dissect the associated molecular mechanism and cellular processes. The goal of our studies is to gain understanding of pancreatic differentiation and maturation processes at single-cell level.

Thesis topic 1: Functional characterisation of a novel pancreatic stem cell population (SCR-1)

In this project we will apply genetic, molecular and in vivo imaging approaches in the model organism zebrafish including cell-ablation, lineage tracing and single-cell RNA-sequencing applications.

Supervisor: Meyer; Co-supervisor: Zwerschke

Thesis topic 2: mTOR signalling in pancreatic tissue maintenance and regeneration (SCR-2)

In this project we will apply molecular, genetic and optogenetic approaches in the model organism zebrafish including transgenesis, biochemical analyses and advanced fluorescence imaging.

Supervisor: Meyer; Co-supervisor: Thedieck

Stemness and ageing in tunicates (SAT)

The Rothbächer lab studies cell fate switching in vivo, utilizing the great cellular and genomic simplicity of developing tunicates, the closest sister group to vertebrates. While the activation of Wnt and FGF signaling is of central importance in the pluripotency context, we recently discovered intruiging novel repressive functions of their nuclear effectors influencing target gene expression and cell fate choice. In parallel to describing the underlying mechanisms in further detail they already open great possibilities for testing the conservation, also in human stemness and the potential for drug mediated control. We use methods of electroporation mediated gain- and loss-of function to monitor transcriptional activity in vivo combined to high-end genomics, imaging and ex-vivo proteomics.

Thesis topic 1: Wnt signalling effectors in stemness and lineage segregation in tunicates (SAT-1)

To study the repressive mechanisms of TCF/ß-catenin, students will perform standard molecular cloning techniques, in vitro fertilizations and in vivo electroporations of ascidian embryos, gene expression assays as well as ex-vivo DNA-protein pulldowns.

Supervisor: Rothbächer; Co-supervisor: Hobmayer/Edenhofer/Zwerschke

Thesis topic 2: FGF/Ets signalling effectors and DOPA in sensory adhesive tissue formation and remodelling (SAT-2)

In this project we will use standard molecular cloning techniques, in vitro fertilizations and in vivo electroporations of ascidian embryos, gene expression assays as well as advanced imaging techniques to study Ets factor repression mechanisms and DOPA function during tunicate development and metamorphosis.

Supervisor: Rothbächer; Co-supervisor: Hobmayer/Edenhofer/Zwerschke