The recent coronavirus pandemic vividly demonstrated the importance of virus research; not only must we understand viruses’ functioning to fight emerging threats but viruses are also useful model systems for the interpretation of complex cellular processes. Being dependent on the host cell for their multiplication, viruses developed diverse strategies to usurp the cellular synthetic machinery for their own benefit. We decided to work on the comparably harmless and simple common cold viruses that belong to the large picornavirus family. Our findings could thus occasionally be extrapolated to more serious human and animal pathogens belonging to the same family.
The common cold usually remains limited to the nasal mucosa, as indicated in the name ‘rhinoviruses (RVs)’. Numerous students were involved in working out how RVs specifically bind to the target cells, which pathways they exploit for gaining access to the cell and how they release their RNA genome for infection. From the released viral RNA ribosomes produce tiny amounts of a viral proteinase that specifically shuts down the synthesis of cellular proteins and exclusively viral proteins are being made. Although tiny, of simple architecture and with a small RNA genome, RVs still leave us open questions to be addressed. My students collaborated with specialists in fields including Structural Biology, Analytical Chemistry, and Biophysics, to just name a few. Work with viruses thus conveys profound general knowledge and training in diverse techniques. Noteworthy, my students came from numerous different countries enriching the mutual understanding of cultures and societies.
Electron microscopy and X-ray crystallography has shown that the attachment points of the viral genomic RNA to the inner wall of the protein shell change on expansion of the particle in vitro. To find out whether the same happens in vivo we shall isolate intermediates of the process from cells shortly after infection and analyse their 3D-structure by cryo-electron microscopy image reconstruction. As we already saw particles lacking a pentamer in negative stain we shall attempt isolating and analysing such particles from infected cells. In parallel, we shall compare the secondary structure of the RNA inside the virion, in the expanded particle, and in refolded RNA by selective chemical modification followed by deep sequencing. Finally, we shall explore the possibility to inhibit RNA exit with compounds binding defined structural elements of the RNA; such compounds might be useful as novel antivirals.
Doctorate at the Université Montpellier, France, Venia Legendi at the Medical Faculty, University of Vienna (Biochemistry), Fellowship of the French Governement, Fellowship of the Ligue Française de la Lutte contre le Cancer, Höchst Preis, Th. Körner Preis, sabbatical in Structural Biology at the IBMB-CSIC, Barcelona, Spain, 176 peer reviewed publications in scientific journals.
Insights into minor group rhinovirus uncoating: the X-ray structure of the HRV2 empty capsid.
Garriga, Damià; Pickl-Herk, Angela; Luque, Daniel; Wruss, Jürgen; Castón, José R; Blaas, Dieter; Verdaguer, Núria
Productive entry pathways of human rhinoviruses.
Fuchs, Renate; Blaas, Dieter
Characterization of rhinovirus subviral A particles via capillary electrophoresis, electron microscopy and gas-phase electrophoretic mobility molecular analysis: Part I.
Weiss, Victor U; Subirats, Xavier; Pickl-Herk, Angela; Bilek, Gerhard; Winkler, Wolfgang; Kumar, Mohit; Allmaier, Günter; Blaas, Dieter; Kenndler, Ernst
Dissecting the turgor sensing mechanisms in the blast fungus Magnaporthe oryzae
Pikobodies: What does it take to bioengineer NLR immune receptor-nanobody fusions
scRNA and phylogenetics
Gene regulatory mechanisms governing human development, evolution and variation
Regulation of Cerebral Cortex Morphogenesis by Migrating Cells
Phage therapy for treating bacterial infections: a double-edged sword
Suckers and segments of the octopus arm
Using the house mouse radiation to study the rapid evolution of genes and genetic processes
CRISPR jumps ahead: mechanistic insights into CRISPR-associated transposons
SLiMs and SHelMs: Decoding how short linear and helical motifs direct PPP specificity to direct signaling
Title to be announced
Enigmatic evolutionary origin and multipotency of the neural crest cells - major drivers of vertebrate evolution
Visualising mitotic chromosomes and nuclear dynamics by correlative light and electron microscopy
Engineered nanocarriers for imaging of small proteins by CryoEM
Bacterial cell envelope homeostasis at the (post)transcriptional level
Title to be announced
Hydrologic extremes alter mechanisms and pathways of carbon export from mountainous floodplain soils
Dissecting post-transcriptional gene expression regulation in humans and viruses
Polyploidy and rediploidisation in stressful times
Prdm9 control of meiotic synapsis of homologs in intersubspecific hybrids
Title to be announced
RNA virus from museum specimens
Programmed DNA double-strand breaks during meiosis: Mechanism and evolution
Title to be announced