My major contribution to teaching, as professor emeritus, is the organization and active participation in the course “Advanced Cell Biology” which I had initiated early on during my tenure. The course consists of a lecture series given by a dozen experts (from in- and outside the Max Perutz Labs) about their research area in the field of molecular cell biology. Their talks (2 x 90 min each) include background knowledge, scientific concepts, recent advances, current research from their own labs, open questions, and visions for the future. In addition, the course comprises student literature seminars on topics related to the lectures. This format enables first-hand presentations of ongoing research projects to students prior to their specialization and at the same time provides a platform for intense mutual personal exchange between students and lecturers. I am also Erasmus coordinator for outgoing students and supervisor for student internships.
The cytolinker protein plectin dictates global cytoskeleton organization and dynamics by recruiting and anchoring intermediate filaments (IF), the mechanically most robust cytoskeletal network component, to strategic cellular structures, such as cell-cell and cell-matrix junctions, nucleus, mitochondria, contractile apparatus, etc. Plectin-mediated IF interlinking affects tissue integrity, polarization and migration potential of cells, mechanotransduction, and stress response. Of special interests to us are the molecular mechanisms that lead to plectinopathies, such as skin blistering, muscular dystrophy, neuropathies, vascular system disorders, and fibrillar protein aggregation. Together with collaborating groups, current emphasis is on plectin’s recently discovered role in brain and sensory neuron, its involvement in invasion and malignant progression of cancer cells, and epigenetic regulation of plectin expression. We apply mouse genetics combined with cell and structural biology.
Gerhard Wiche (Professor Emeritus) studied Biochemistry/Chemistry at the University of Vienna (PhD 1971). After 5 years as postdoctoral fellow and research associate in the USA (Roche IMB, NJ; UC Berkeley, CA), he started his own group at the Medical School and in 1990 took a position as Full Professor for Molecular Cell Biology at the University of Vienna (sabbaticals: Chicago, Paris, Madrid).
Contributions to Science: 174 publications (up to 2020), plus 15 book chapters and invited reviews
Bibliography: https://pubmed.ncbi.nlm.nih.gov/?term=Wiche+G%5BAuthor%5D&sort=pubdate
Orcid ID: 0000 0001 9550 5463
Plectin’s isoform diversity is based on alternative splicing of multiple first exons leading to the expression of protein variants with unique N-terminal domains. These domains specify distinct interaction partners, enabling differential isoform targeting. As all isoforms are endowed with a universal, high affinity IF-binding domain at their C termini, they recruit and anchor IF networks of any type to their target sites. The cell type and developmental stage dependent expression of isoforms in different combinations and proportions leads to isoform-dependent interlinking of different cellular structures and organelles, with consequences for cytoarchitecture, cell-cell and cell-matrix interactions, signaling, and migration potential of cells. In addition, plectin consolidates IF networks physically by filament crosslinking. (Wiche et al, Curr Opin Cell Biol 2015)
Plectin deficiency in skeletal muscle leads to myopathies manifesting with IF network collapse, protein aggregate formation, misalignment and sarcolemma-decoupling of myofibrils, dislocation and dysfunction of mitochondria, as well as structural and functional distortions of nuclei and neuromuscular synapses. These pleiotropic effects are due to the loss of one, or more, of the four major plectin isoforms that in mature myofibers are differentially targeted and recruiting desmin IFs to the sarcolemma, contractile apparatus, myonuclei, and mitochondria. Using differentiation competent myoblast cell cultures established from plectin-KO mouse muscle, we found a chemical chaperon (4-PBA) that alleviates protein aggregation and increases muscle strength in mice, setting the stage for clinical studies. (Winter et al, J Clin Invest 2014)
Skin blistering is the hallmark of most plectinopathies. We showed that plectin is a crucial component of the hemidesmosome (HD) junctional complex and a direct binding partner of integrins. The loss of isoform P1a leads to disruption of the connection between the intracellular keratin filament bundles (K) and the extracellular matrix, resulting in nonfunctional and less HDs. The analysis of transgenic mice mimicking the dominant human plectin EBS-Ogna mutation provided new insights into pathomechanisms and revealed a general HD-stabilizing mechanism based on lateral self-association of plectin’s ~200 nm long α-helical rod domains (see oligomerized plectin molecules). (Walko et al, PloS Genet 2011)
Astrocytes play a prominent role in many brain activities. With their unique star-shaped morphology, astrocytes enwrap synapses and assume various anatomical links with neuronal processes, thereby affecting the formation and stability of synapses in their response to neuronal activity. There is evidence for an involvement of plectin in astroglia disorders, such as Alexander disease, and a significant upregulation of plectin has been observed in patients with temporal lobe epilepsy or a history of psychosis; plectin is also substantially increased in Alzheimer’s hippocampus. We have shown that P1c, the plectin isoform associating with microtubules, is implicated in axonal vesicle transport and long-term memory formation (Valencia et al, Neuropathol Appl Neurobiol. 2021). Thus, it will be a challenging task to establish mechanistic links between astrocyte-based neurologic diseases, cognitive dysfunctions, and plectin-related cytoskeleton deregulation.
I am currently involved in several collaborations with research groups working on plectin, and I am particularly committed to sharing knowledge and passing on laboratory made materials (transgenic mice, cell lines, antibodies, recombinant expression constructs) to junior colleagues.
John Loughlin, Tony Sorial, Farshid Guilak
Skeletal Research Group, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
Department of Orthopedic Surgery, Washington University in St. Louis, St. Louis, Missouri, USA
Robert Zorec, Jernej Jorgacevski, Maja Potokar
LN - MCP, Institute of Pathophysiology, School of Medicine, University of Ljubljana, Slovenia
Kimberley Kelly
Department of Biomedical Engineering and Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia, USA
Gijsje Koenderink
TU Delft Faculty of Applied Sciences, Department of Bionanoscience, Kavli Institute of Nanoscience, Amsterdam, The Netherlands
Martin Gregor
Laboratory of Integrative Biology, Institute of Molecular Genetics of the ASCR, Prague, Czech Republic
Ryan Petrie
Department of Biology, Drexel University, Philadelphia, Pennsylvania, USA
Lilli Winter
Neuromuscular Research Department, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria
Richard Hayward
Department of Pathology, University of Cambridge, Cambridge, UK
Voyage of the Starships: giant transposons as crucibles of evolution
Parthenogenesis, cryptobiosis, and the survival in extreme environmental conditions
Evading ageing: Mitochondrial and proteostatic adaptations in oocytes
Genomes in Rhodnius prolixus symbiotic system
Stem cells, immune evasion and metastasis in colorectal cancer
Ubiquitin & Friends Symposium 2024
The Ubiquitin & Friends Symposium is an annual international meeting taking place in the beautiful capital of Austria, aiming to bring together scholars from various fields studying ubiquitin/Ubl biology and protein degradation in a personal, family-like atmosphere, as suggested by the name.
The evolution and development of mollusc shells
Unraveling the Complexity of Crossover Regulation in C. elegans
Dynamics of 3D Genome Structure and Function
How superworms can help to solve our plastic waste crisis
Title to be announced
New players in an old pathway: biology of methanogens of the TACK superphylum
Shaping morphogen gradients: from molecules to tissues and back
Title to be announced
Studying stressed cells by in situ structural biology
Exploring Microbial Resilience: Unravelling Escherichia coliand#x27;s Stress Response at the Level of Protein Synthesis
Arbuscular mycorrhiza development and function
Deep homology and deep diversity: Evolving genetic toolkits for making and sensing light
The evolution of cell type identity and tissue microecology at the fetal-maternal interface
The unanticipated roles of PICIs and phages in bacterial evolution
Chemical targeting of subcellular protein localization
Origin and diversification of gut-derived organs in chordates
Job's Dilemma for the Genome: Why Bad Things Happen to Good Chromosomes
Connections between carbon and nitrogen cycling in the ocean
Understanding how the DNA-loop-extruding protein complex Condensin folds a chromatinized genome into mitotic chromosomes
DrugMap: A quantitative pan-cancer analysis of cysteine ligandability
From Roads to Rivers? Occurrence and environmental fate of tire and road wear particles and of tire-related chemicals
FENS 2024 Satellite event: Home cage behavior monitoring at the interface of animal welfare and neuroscience
Striking physiology and cell biology of (marine) environmental microorganisms
Mechanisms controlling maintenance of cohesin dependent loops
Title to be announced