Time for lunch
Aggregated, misfolded proteins need to be removed by cells to avoid their build-up. Failure to do so often leads to disease. During a process called aggrephagy, aggregated proteins are marked with ubiquitin and clustered into molecular condensates, which are then degraded with the help of the autophagic machinery. In a new study published in EMBO Journal, Bernd Bauer, a PhD student in the Martens group, reveals how the cargo receptor protein TAX1BP1 facilitates the switch from cargo collection to autophagosome formation. Bernd’s findings show that TAX1BP1 recruits pro-autophagic factors to initiate autophagosome biogenesis by sensing the amount of ubiquitin within the cargo.
Controlling condensation by phosphorylation
Condensate formation as an organizing principle is rapidly gaining traction in many biological processes. However, the mechanisms by which the size, composition and subcellular localization of these condensates are regulated are largely unknown. Harald Hornegger, a PhD student in the Karagöz lab, has revealed that phosphorylation of the RNA-binding protein IGF2BP1 significantly impacts the biogenesis, size and number of stress granules. The study, published in Nature Communications, shows that post-translational modification of intrinsically disordered regions of IGF2BP1 alters its condensation properties, a mechanism which the authors propose allows cells to tune their transcriptional output in response to specific environmental conditions.
Kristina Djinovic-Carugo named Ambassador of Science of Slovenia
This award recognizes significant achievements in the field of scientific research and development by Slovenians abroad. By appointing distinguished researchers as Science Ambassadors, the Ministry of Science of the Republic of Slovenia seeks to foster cross-border partnerships and inspire future generations of scientists.
Staying mobile
Lamins are proteins that provide structural support to the cell nucleus by forming a fibrous mesh beneath the nuclear membrane called the nuclear lamina. In addition to providing structural support, soluble lamins and lamin-associated proteins (LAPs), play a crucial role in organizing chromatin and regulating gene expression. The molecular mechanisms that underlie these processes, however, remain unclear. In a recent Nucleic Acids Research publication, the Foisner lab revealed that LAP2α drives muscle cell differentiation by controlling the distribution of lamins A and C on chromatin.
Arndt von Haeseler retires at the Max Perutz Labs
Throughout his career, Arndt von Haeseler studied two fundamental questions in evolutionary biology: What are the evolutionary forces that have shaped the genomes of contemporary organisms, and how can we infer the relevant parameters from multiple sequence alignments? He has focused on developing mathematical, statistical, and computational tools to analyze the vast amounts of data generated by high-throughput technologies.
“Humans evolved to be storytellers”
Erinc Hallacli, originally from Türkiye, obtained his PhD at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. For his postdoctoral studies, he moved to the Whitehead Institute for Biomedical Research in Cambridge, USA to work on protein aggregation sensors and RNA binding prions. Erinc shifted his focus to investigate Parkinson’s Disease when he relocated to Brigham and Women’s Hospital in Boston, USA, where he also was appointed Assistant Professor in Neurology in 2023. Now based in Vienna, Erinc is a junior group leader at the Perutz and Assistant Professor at the Medical University of Vienna. In our interview, he shares insights into his research and passion for science.
Who let the FoxO in?
Pluripotent embryonic stem cells eventually give rise to the development of a healthy organism, complete with more than 300 fully differentiated cell types. The mechanisms by which they undergo differentiation, however, are not fully understood. In a new study published in Nature Communications, first author Laura Santini, a former PhD student in the Leeb lab, investigated how naïve pluripotent stem cells execute the first cell fate decision of the early post-implantation embryo. The researchers discovered a crucial role of FoxO transcription factors in ensuring the orderly and timely shift from the naïve to the formative state during embryonic stem cell development.
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.
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