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.
Survival of the filamentous
Organisms often have to ensure their survival during periods of unfavorable environmental conditions. Through the process of meiosis, budding yeast cells haploidize their genome and package it into environmentally resistant spores. In their publication in Cell, Joao Matos and his team discovered that metabolic enzymes essential for the recovery from spore dormancy form protein filaments during meiosis. In collaboration with the Pilhofer lab at the Eidgenössische Technische Hochschule (ETH) in Zurich, Matos and his team developed a novel workflow that combines the preparation of cell spreads with multimodal imaging that enabled the study of these filaments with unprecedented detail. The work implicates a previously unanticipated organization of proteins in the cell that permits long periods of dormancy.
All eyes on the proteome
Sexual reproduction involves the formation of gametes, specialized male and female reproductive cells. Gamete formation involves a process called meiosis where DNA is segregated into daughter cells, each containing half the genomic content of the adult cells. In their study published in Developmental Cell, Joao Matos and his collaborators characterized the composition and phosphorylation status of the proteome during meiosis, using budding yeast as a model system. They found that sequential waves of protein expression and phosphorylation rewire the proteome to enable gametogenesis. They also discovered that mitochondrial enzymes, such as ATP synthase and Aldehyde dehydrogenase, are regulated by phosphorylation during gametogenesis.
Unrecyclable: how protein aggregates evade clearance
Protein aggregates are a common hallmark of neurodegenerative diseases. These aggregates accumulate despite dedicated cellular surveillance mechanisms to prevent the build-up of unfolded or damaged cellular components. In a study published in Science Advances, Luca Ferrari, a postdoctoral researcher in the Martens group, compared how monomeric and pathological Tau proteins are targeted by this surveillance machinery. The team found that while Tau monomers are degraded normally, Tau fibrils, a hallmark of Alzheimer’s Disease, evade clearance by preventing the binding of a crucial mediator, TAX1BP1, which helps to recruit the autophagy machinery.
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