PhD thesis topics at DP ARDRE

Adipose stem cells in obesity and caloric restriction (ASC)

StemCells_CaRe_Requirements: Applicants should have a strong background in Molecular Biology, Cell Biology or Biochemistry and must be highly motivated team players with strong interest in life sciences.

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.

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

The successful applicant 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

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

The successful applicant 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)

Scientific_background_image_2Voltage-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.

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

The young researcher 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

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

The young researcher 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

 

Chemical synthesis of anti-ageing natural products (CAP)

Requirements: Strong theoretical and practical background in organic (retro)-synthesis of complex molecules. Experience in the analysis of (2D)-NMR spectra and structure elucidation.

Scientific_background_image_1Natural 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.

Natural products for regulation of mitochondrial function (CAP-1)

The successful applicant 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

Chemical synthesis of anti-ageing natural products (CAP-2)

The successful applicant 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)

hobmayer_i

Requirements: Theoretical background in stem cell/regeneration research. Strong practical background in standard molecular techniques. Experience in genetic interference methods.

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.

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

The successful applicant will apply methods of gene expression, pharmacological and genetic interference, genetic transformation, and transmission electron microscopy.

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

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

The successful applicant 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_K_1Requirements: M. Sc. in life sciences or related discipline. Background in cell biology and biochemistry required. Knowledge in imaging, mass spectrometry of proteins and/or metabolites and/or computational biology will be a strong plus. Strong communication skills in English (written and spoken) are a must.

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.

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

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)

Requirements: MIA-1: strong theoretical and practical background in cell culture techniques; experience in 3D organotypic cell culture models desirable. Experience in antibody-based technologies, such as Western Blot, Immunohistochemistry, Immunofluorescence and gene expression analysis. MIA-2: strong theoretical and practical background in protein expression, purification, and characterization, experience in drug design desired. Experience in cell culture technologies.

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.

Sk_EqRole of mitochondrial quality control in skin ageing (MIA-1)

The successful applicant 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

PJD_FAHD1 inhibitors in ageing and cancer research (MIA-2)

The successful applicant 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 regeneration (MAR)

Liedl_Thes_TpcsRequirements: MSc. in chemistry or related discipline. In depth knowledge of computational chemistry, esp. chemoinformatics and bioinformatics, and structural biology. Experience in biophysics, structural modelling, pattern recognition, application of force fields, computer simulations, programming and statistics is desired.

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.

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

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

The successful applicant 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)

___Bild1_SRequirements: Theoretical and practical background in analytical and preparative separation techniques is suggested.

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.

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

The successful applicant 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

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

The successful applicant 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)

EdenhoferRequirements: Applicants should have a strong background in cell biology and neurobiology. Experience in human (stem) cell culture and/or CRISPR/Cas genome engineering is desired. Basic experience in bioinformatics approaches.

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.

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

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)

RequirementsStrong background in plant physiology and biochemistry. Experience with -omics techniques, especially metabolomics is desirable. Excellent team work and communication skills and the ability to work

Thesis_topic_IK_1independently are essential.

The Kranner lab investigates responses of plants to stress on the biochemical, physiological and molecular level. Using an  updated version of the stress model by János Selye, one of the most widely accepted biomedical stress models, the group is working on deciphering the various phases of stress, from "alarm" and "resistance" – corresponding to "eustress" and conferring tolerance – to "exhaustion". The latter is equivalent to distress, leading to deterioration, ageing and ultimately, death. Seeds are particularly useful models to study stress, as they can be aged 
Thesis_topic_IK_2artificially and their viability assessed through gemination tests. Studying the mechanisms of plant and seed viability has also important socio-economical aspects: all food is directly or
indirectly derived from plants, and seeds are the most
important basis of human and animal nutrition.
Ageing in the plant Arabidopsis thaliana and potential roles of FAHD1 homologues (PA-1)

The successful applicant 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

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

The successful applicant 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)

dm-Requirements: Strong theoretical and practical background in molecular biology, cell biology and cell-signaling. Experience with fluorescence microscopy and with animal models.

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.

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

The successful applicant 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

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

The successful applicant 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)

Grafik_URRequirements: Strong theoretical and practical background in molecular embryology, cloning and biochemistry techniques. Experience with tunicates would be a plus.

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.

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

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

The successful applicant 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

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