Postdoc-Pool Projects Medical University of Graz

Deciphering the lipid-sensing machinery of TRPC channels - a step towards neuro-optopharmacology

Contact person:
Univ.-Prof. Mag. Dr. Klaus Groschner
Institute of Biophysics
E-mail: klaus.groschner(at)medunigraz.at
Phone: +43 (0)316 380 – 4135

BioTechMed-Graz Postdoc: Michaela Lichtenegger, Mag.pharm. Dr.rer.nat.

Research partners:

Univ.-Doz. Dipl.-Ing. Dr. Georg Papst, Institute of Molecular Biosciences, University of Graz
Ass.-Prof. Mag. Dr. Thoma Glasnov, Institute of Chemistry, University of Graz
Ass.-Prof. Dipl.-Ing. Dr. Heinz Amenitsch, Institute of Inorganic Chemistry, Sincrotrone Trieste Group, Graz University of Technology

Canonical transient receptor potential (TRPC) proteins are unique lipid sensing molecules, which form ion channels involved in muscle and neuronal (patho)physiology. Precise spatial and temporal control of TRPCs by optogenetics or optopharmacology is considered as a highly attractive therapeutic avenue. We aim to unravel the TRPC lipid sensing machinery, establish a mechanistic model of lipid gating in TRPCs and to develop tools for their optical control in tissues. In an initial step, we will reconstitute purified TRPC proteins in liposomes and planar lipid bilayers. Defined changes in the channels lipid environment will be introduced by photolysis of caged lipids. Small-angle x-ray scattering will be employed to determine changes in membrane physical parameters and membrane structural kinetics with sub-ms time-resolution in response to changes in lipid composition. Channel complex organization and function will be analyzed by electrophysiology and fluorescence (FRET) microscopy, and lipid-sensitive gating elements within TRPCs will be identified by structure-guided mutagenesis. Based on this knowledge, optogenetic- and optopharmacological tools will be designed, generated and tested in neuronal cells. We aim to provide proof of principle for optical control of TRPCs as a suitable approach to govern tissue function in a contact free manner and with unprecedented spatial and temporal precision.

The cerebrovascular sphingolipid rheostat as modulator of blood-brain barrier function under inflammatory conditions

Contact person:
Wolfgang Sattler, Ao. Univ. Prof.,
Institute of Molecular Biology and Biochemistry
E-mail: wolfgang.sattler(at)medunigraz.at
Phone: +43 (0)316 380 – 4188

BioTechMed-Graz Postdoc: Madeleine Göritzer, Mag.rer.nat. PhD.

Research partners:

Juliane Bogner-Strauß, Assoc.Prof., Institute of Biochemistry, Technical University of Graz
Sepp D. Kohlwein, Univ.-Prof., Institute of Molecular Biosciences, University of Graz, BioImaging Graz
Gerald Rechberger, Ass. Prof., Institute of Molecular Biosciences, University of Graz

The neurovascular unit separates most regions of the brain from the circulation and maintains the specialized micromilieu of the CNS. Brain endothelial cells (BMVEC) constitute the morphological basis of the blood-brain barrier (BBB) by the formation of tight junction (TJ) complexes. The presence of TJ prevents paracellular transport of molecules and cells and maintains brain homeostasis via elaborately regulated transport mechanisms. Loss of BBB function under inflammatory conditions favors the development of neurodegenerative diseases.
We propose that inflammation-induced alterations in sphingolipid (SL) homeostasis in brain endothelial cells drive BBB dysfunction. At the BBB, SLs are essential components of lipid rafts that contribute to TJ formation, cellular adhesion and correct transporter patterning. Pro- and antiapoptotic SL species, namely ceramide (Cer) and sphingosine-1-phosphate (S1P), regulate cell fate via the so called “sphingolipid rheostat”.
Using in vitro, ex vivo, and in vivo models we will clarify the impact of cold and hot inflammatory conditions on brain endothelial sphingolipid composition and synthesis and the impact on BBB function. Pharmacological modulation of SL synthesis and signaling will reveal whether this approach holds promise to normalize brain endothelial SL patterns and rescue BBB function under inflammatory conditions in vivo.

From Structure to Function – Metagenomics for Functional Analyses and Modeling of Microbiome Data

Contact person:
Univ.-Prof. Dr.med.univ. Gregor Gorkiewicz
Institute of Pathology
E-mail: gregor.gorkiewicz(at)medunigraz.at
Tel.: +43 (0)316 316 380 – 7655

BioTechMed-Graz Postdoc: Bettina Halwachs, Dipl.-Ing. Dr.techn. BSc

Research partners:

Dr. Gerhard G. Thallinger, Bioinformatics Group, Institute for Knowledge Discovery, Graz University of Technology
Ao. Univ.-Prof. Dr. Christoph Högenauer, Division of Gastroenterology and Hepatology Department of Internal Medicine, Medical University of Graz

The human microbiota is a complex community of microbes with enormous implications for health and disease. Up to now microbiota analysis has mainly focused on the phylogenetic composition of the microbiota and its alteration during disease (e.g. by means of 16S rDNA analysis). Although tremendous variation exists between the microbiotas of healthy individuals, clear associations to host phenotypes including inflammatory (e.g. rheumatoid arthritis, IBD) and metabolic (e.g. obesity, diabetes) diseases, as well as cancer (e.g. colorectal cancer) were demonstrated.
The project’s aim is to deepen our understanding of “what is a physiologic vs a pathologic microbial community type” by using the results of previous 16S rDNA-based microbiota studies and associate them with higher levels of microbiota-host interactions (e.g. by means of metabolomic modeling).
Therefore, it is necessary to identify and to describe the main community characteristics within physiologic and pathologic community types. In addition, microbiome analysis has to be expanded to a functional, i.e. metagenomic level (sequencing of the whole genetic information of the microbial community). This allows for the assessment of the genetic coding potential of the microbial community, which gene products or metabolites are produced or not produced under certain (e.g. disease) conditions.

Brain, Ears & Eyes - Pattern Recognition Initiative

Contact person:
Peter B Marschik, Assoc. Prof. PD Mag. DDr.
Research Unit iDN – interdisciplinary Developmental Neuroscience
Institute of Physiology, Center for Physiological Medicine
E-mail: peter.marschik(at)medunigraz.at
Phone:+43 (0)316 380 – 4276

BioTechMed-Graz Postdoc: Robert Peharz, Dipl.-Ing. Dr.techn.

Research partners:

Christian Enzinger, Assoc. Prof. PD Dr., Research Unit Neuronal Plasticity & Repair, Department of Neurology and Division of Neuroradiology, Department of Radiology, Medical University of Graz
Andreas Fink, Assoc. Prof. Mag. Dr., Institute of Psychology, University of Graz
Ralf Vollmann, Ao. Univ.-Prof. Mag.Dr., Institute of Linguistics, University of Graz
Franz Pernkopf, Assoc. Prof. DI Dr., Signal Processing and Speech Communication Laboratory,Graz University of Technology
Barbara Schuppler, Mag. Dr., Signal Processing and Speech Communication Laboratory, Graz University of Technology

The “Brain, Ears & Eyes – Pattern Recognition Initiative” (BEE-PRI) aims to contribute to the early/earlier identification of neurological disorders to enhance intervention and counseling. Our objective is to break new ground in a broad interdisciplinary approach with a life-span perspective: we will focus on neurodevelopmental but also neurodegenerative phenomena and hence refrain from labeling BEE-PRI as a single research project. This initiative should be understood as a growing interdisciplinary research network and synergetic conglomerate of scientists covering a multitude of disciplines: cognitive sciences, education, linguistics, speech-language pathology, neurology, pediatrics, physiology, psychiatry, psychology, radiology, signal processing, and machine learning. BEE-PRI will combine established methods, such as fMRI, EEG, ERP, eye-tracking, and audio-video analysis, with novel interdisciplinary approaches (e.g., Observing-the-Observer, automated detection of behavioral biomarkers, probabilistic modeling). BEE-PRI-BioTechMed is an endeavor to learn about and better understand neuro(mal)development and neurodegenerative processes, detect new neurofunctional and neurostructural biomarkers to enhance earlier diagnosis, predict developmental trajectories, and facilitate earlier intervention.

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Postdoc-Pool Projects Medical University of Graz