Network-based approaches open a new avenue to classify and treat rare diseases
Scientists at CeMM, the Max Perutz Labs, and St. Anna Children’s Cancer Research Institute have achieved a significant advancement in the research of rare immune system disorders. Through a network-based approach, they have reclassified approximately 200 rare diseases. Initial comparisons with clinical data already demonstrate how this can enhance the prediction of treatment efficacy. Moreover, the study reveals for the first time the strong similarities between the molecular mechanisms of rare diseases and autoimmune and autoinflammatory conditions, such as chronic inflammatory bowel disorders, multiple sclerosis, and specific types of diabetes. The study has now been published in Science Advances.
Prestigious fellowships awarded to Max Perutz Labs PhD students
Congratulations to Johannes Benedum, Elisabeth Holzer, and Alexandra Shulkina who have been awarded DOC Fellowships by the Austrian Academy of Sciences (ÖAW). Furthermore, congratulations to Anzhela Pavlova, who has received a BIF Fellowship from the Boehringer Ingelheim Fonds. Both programs offer funding for highly qualified doctoral candidates. This year’s fellowships support projects on DNA repair mechanisms, regulation of RNA polymerases, and mammalian autophagy.
Lipid Chemistry Empowers Nuclear Shape
The cell nucleus is surrounded by a spherical double membrane called the nuclear envelope. Scientists have long been intrigued by how this envelope can be elastic enough to accommodate shape changes that cells experience as they move through tissues, but also rigid enough to maintain nuclear integrity. A study by Anete Romanauska and Alwin Köhler, published in Nature Cell Biology, uncovers that the chemistry of membrane lipids is key for this versatility. When this chemistry is perturbed, the nuclear membranes become stiff and prone to rupture, and nuclei lose their typical round shape and morph into a polyhedron.
"In science, you can’t get bored"
Irma Querques studied Biotechnology at the University of Bologna and received a PhD at the European Molecular Biology Laboratory (EMBL) in Heidelberg. Before joining the Max Perutz Labs in 2023, she worked in the lab of Martin Jinek at the University of Zurich as a postdoctoral fellow, studying CRISPR-guided transposons. We talked to her about the medical potential of her research on transposons, what science has to do with a good TV series, and how she gave up her dream of becoming a book author to tell stories about how molecular processes work.
START grant for Stephanie Ellis
Congratulations to Stephanie Ellis, who has been awarded a START grant totaling € 1.05 million by the Austrian Science Fund FWF. Together with the Wittgenstein Award, the FWF START grant is one of the most prestigious and highly endowed scientific awards in Austria. The funding will support Stephanie’s work on cell competition over the next five years.
Many roads lead to Rome
Cilia are hair-like projections on the surface of eukaryotic cells that perform essential sensory and motile functions. Defects in cilia are associated with a wide range of human diseases, collectively known as ciliopathies. In work recently published in The EMBO Journal, the lab of Alex Dammermann has identified the core set of genes associated with cilium biogenesis and function, which includes an additional 152 previously uncharacterized genes. The authors’ compendium of ciliogenesis factors provides an invaluable inventory for the further investigation of this important cellular organelle.
€1.2 million in grants awarded to Max Perutz Labs scientists
Thomas Leonard, Shotaro Otsuka, and Gijs Versteeg have been awarded individual project grants, amounting to approximately €400.000 each, by the Austrian Science Fund FWF. The scientists’ projects will deal with kinases involved in neurodevelopmental disease, the regulation of viral restriction factors, and intra-cellular communication. Congratulations!
Alwin Köhler named a Moore Distinguished Scholar at Caltech
Scientific Director Alwin Köhler has been selected by the California Institute of Technology for its prestigious Moore Distinguished Scholar Program. The scholarship was established in 2000 by Gordon Moore and his wife Betty. Moore, a pioneer of the modern electronics industry and a philanthropist, was cofounder of Intel and instrumental in establishing Silicon Valley.
HFSP grant awarded to Kristina Djinovic and Jonas Ries
The Human Frontier Science Program (HFSP) has awarded a research grant amounting to €1.5 million over the next three years to Kristina Djinovic-Carugo, incoming group leader Jonas Ries, and scientists from the University of Connecticut (USA) and the University of Yamanashi (Japan). The project team will combine their expertise to understand the role of liquid-liquid phase separation in the biogenesis of the complex protein assemblies found in striated muscle.
Keeping the immune system in check
Tristetraprolin (TTP) is an important regulator of the innate immune system that modulates the inflammatory response. How TTP is regulated, however, is poorly understood. In new work published in eLife, the lab of Gijs Versteeg has gained insight into how this critical immune regulator is kept in check. The team, which includes the labs of Pavel Kovarik (Max Perutz Labs), Tim Clausen and Johannes Zuber (Research Institute of Molecular Pathology, IMP), identified the ubiquitin E3 ligase HUWE1 as an important factor that controls the degradation of TTP.
Elucidating the mechanism behind the medicine
The precursor of UCB0599, a potential drug to treat Parkinson’s disease, has been shown to reduce aggregation of the protein alpha synuclein in mice. Although currently being evaluated in a phase 2 clinical trial in human patients, UCB0599’s mode of action is unknown. The lab of Robert Konrat has determined high-resolution structures of membrane-bound alpha synuclein. Their findings, published in the Proceedings of the National Academy of Sciences, reveal a putative mechanism by which UCB0599 interferes with pathogenic protein aggregates.
Win some – lose some: how cells adapt to aneuploidy
An abnormal number of chromosomes, known as aneuploidy, is a common feature of many human cancers. Most cancer types harbor specific patterns of these chromosomal abnormalities, but why certain chromosomes are selected for gain or loss while others are not is poorly understood. In work published in Genes & Development, the lab of Christopher Campbell has now managed to recapitulate some of the aneuploidy patterns seen in cancer cells in the lab. They were able to identify specific genes that are responsible for the selection of certain aneuploidies for the first time in human cells.
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