Alwin Köhler reappointed as scientific director of the Max Perutz Labs
Alwin Köhler has been appointed as scientific director of the Max Perutz Labs for an additional four-year term. Since starting in 2020, he has successfully led the institute through a period of significant transformation. His second four-year term will begin on October 1, 2024.
Disordered by design
During periods of protein folding stress, the transmembrane protein IRE1 detects misfolded proteins in the endoplasmic reticulum (ER) and initiates a transcriptional relay as part of the unfolded protein response (UPR). In order to signal the presence of unfolded proteins in the ER, IRE1 oligomerizes, but the molecular mechanisms behind this process remain unknown. In a recent study from the Karagöz lab published in EMBO Journal, first authors Paulina Kettel, PhD student and Max Perutz Fellowship awardee 2022, and Laura Marosits, then research associate, provide the first evidence that disordered regions in IRE1’s ER luminal sensor domain regulate its self-assembly. Their discoveries could help pave the way for the development of drugs that target diseases associated with protein misfolding.
DOC fellowships for Perutz PhD students
The DOC Fellowship program of the Austrian Academy of Sciences (ÖAW) is designed to support highly qualified PhD students by providing funding for their scientific projects. Congratulations to this year’s Max Perutz Labs awardees, Milica Mihailovic and Raquel Silva. Milica investigates ubiquitin-like modifiers as post-translational modifications and their importance for protein quality control. Raquel's work focuses on endothelial cells and their mechanical stress response during the development of cardiovascular diseases.
Man is but a worm (with some small differences)
Gene silencing via RNA interference (RNAi) pathways, a defense mechanism against transposable elements, is evolutionarily conserved and mediated by small RNAs (sRNAs). The exoribonuclease MUT-7 plays a key role in generating the sRNAs. In a recent study published in Nucleic Acids Research, first author Virginia Busetto, a post-doctoral researcher in the lab of Sebastian Falk, characterized MUT-7, revealing that its C-terminal domain exhibits species-specific variations that may serve unique functions.
Vallee Scholarship for Perutz group leader Irma Querques
Congratulations to Irma Querques on being named a 2024 Vallee Scholar. The Vallee Foundation recognizes outstanding, young, independent investigators and supports career development in basic biomedical research. Over the next four years, the foundation will provide funding of $340,000 to support Irma's study on how transposons, also known as ‘jumping genes’, operate, and on exploring their potential technological applications.
Nuclear pore basket - octopus-like arms unveiled
The nuclear pore basket is a filamentous structure attached to the nucleoplasmic side of the nuclear pore complex (NPC), crucial for regulating transport between the nucleus and cytoplasm. In a paper published in Nature Cell Biology, Edvinas Stankunas and Alwin Köhler revealed the structural basis of the basket filaments and their docking mechanism to the main body of the NPC. They explain how the basket can dynamically change its shape, much like the arms of an octopus, to accommodate transport needs, offering new insights into its flexibility and functional plasticity.
A collaborative ORFventure
A Vienna BioCenter campus-wide collaboration involving Perutz group leader Stefan Ameres, Julius Brennecke and Ulrich Elling from the Institute of Molecular Biotechnology (IMBA), and Alexander Stark from the Research Institute of Molecular Pathology (IMP), has developed a method called ‘ORFtag’ to systematically tag proteins and investigate their function in mammalian cells. The innovative, time- and resource-efficient technique enables genome-wide screens of protein functionality. The study is published in Nature Methods.
Two negatives make a positive
Antagonists that are themselves antagonized play a common regulatory role in molecular biology. Peter Schlögelhofer, along with first author Ignacio Prusén Mota and their team, has now identified that the WAPL antagonist SORORIN is not confined to vertebrates but evolutionarily conserved, also to be found in Arabidopsis thaliana and Schizosaccharomyces pombe. Furthermore, they obtained the first in vivo evidence that SORORIN antagonizes WAPL, which is in turn a cohesin antagonist. The study, published in Nature Communications in collaboration with the lab of Jan Michael Peters (Institute of Molecular Pathology), provides valuable insights into the molecular regulation of chromosome segregation in mitotic and meiotic cells.
Finding needles in haystacks: The FACS facility
The Perutz has a range of cutting-edge scientific facilities designed to support its research groups. Among these, the BioOptics Fluorescence Activated Cell Sorting (FACS) facility provides state-of-the-art cell and large particle sorting technologies, analysis tools, and expert support. The second part of our ‘Scientific Facilities - Behind the Scenes’ series features the Perutz FACS facility, showcasing the team and equipment that supports cutting-edge research at the Perutz.
Max Perutz PhD fellowship for pioneering projects
The most ambitious and ground-breaking PhD projects at the Perutz are honored with the Max Perutz PhD Fellowship. Lucas Piëch (Leonard lab) and Clara Schimmer (Ellis lab) have been awarded this year’s fellowship. Lucas will investigate the regulatory mechanisms that control cellular and organismal growth, while Clara will study the cellular mechanics which enable cell competition in mouse epidermal development.
Damage control: Targeting mitochondria
Deficiency in mitophagy, a process by which damaged mitochondria are selectively degraded to maintain cellular health and homeostasis, is a hallmark of neurodegenerative diseases such as Parkinson’s. The molecular mechanisms that govern the initiation of mitochondrial degradation and subsequent autophagosome biogenesis, however, are not well understood. In their new publication in Nature Structural and Molecular Biology, first author Elias Adriaenssens, a post-doctoral researcher in the Martens lab, shows that the TBK1 kinase adaptors NAP1 and SINTBAD play crucial roles during mitochondrial degradation by controlling pathway initiation and driving its efficient progression.
You shall not pass
Communication between organelles and the nucleus is crucial for cellular processes, yet it remains almost entirely enigmatic. In a new study published in EMBO Reports, Shotaro Otsuka and his PhD student Helena Bragulat-Teixidor, Max Perutz PhD Fellowship awardee 2021, reveal the morphology of junctions between the endoplasmic reticulum (ER) and the nucleus. These junctions have a distinctive hourglass shape, which differentiates them from junctions within the ER, implying a putative gatekeeper function between the ER and the nucleus.
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