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.
Learning from viruses
Marco Hein obtained his PhD under the supervision of Matthias Mann at the Max Planck Institute of Biochemistry (Germany), where he used proteomics to map the human interactome. Working as an EMBO postdoctoral fellow with Jonathan Weissman at the University of California, San Francisco (USA), he became interested in virus-host interactions. Marco joined the Max Perutz Labs from the Chan Zuckerberg Biohub (USA), where he was a research fellow. We talked with him about the excitement of discovering something new and what we can learn from viruses about our cells and from viral pandemics about science.
Embryos gaining independence
After fertilization, the genome of the embryo is transcriptionally inactive and maternally deposited RNA and proteins perform cellular functions. During a process called maternal-to-zygotic transition (MZT) the zygotes’ own transcriptional program is activated and maternal transcripts are cleared. The labs of Stefan Ameres (Max Perutz Labs, Institute of Molecular Biotechnology, IMBA) and Andrea Pauli (Research Institute of Molecular Pathology, IMP) have developed a method that allowed the scientists to gain detailed insights into the organization of gene expression during this first major developmental transition in the life of vertebrates. Their findings have now been published in Cell Reports.
Do it yourself – kinase activation revisited
The transmission of information in cells often involves the modification of proteins by the addition of phosphate groups, a process termed phosphorylation. Phosphorylation is catalyzed by protein kinases, which themselves often require phosphorylation for their activation. Some kinases auto-activate by phosphorylating their own activation loop, a process that is usually accomplished by a second copy of the same protein. In work published in Proceedings of the National Academy of Sciences (PNAS), the lab of Thomas Leonard has discovered, unexpectedly, that protein kinase D (PKD) activates itself without the need for another copy of PKD.
Stressing out the immune system
During infection, specialized cells of our innate immune system mount an immediate response to combat invading pathogens. The activation of these immune cells by interferon signaling is key to the resolution of infection. How interferon signaling interacts with other cellular signaling pathways is unclear. The lab of Thomas Decker has now studied the interaction between interferon and stress signaling. Their findings, published in Science Signaling, show that cross-talk between the two pathways modulates immunity in response to infections.
Grant strengthens life science IT infrastructure at the Max Perutz Labs
The Austrian Federal Ministry of Education, Science and Research has awarded a ‘Data Life’ grant to the Max Perutz Labs and the University of Vienna. The €1.9 million grant will be used to provide high-performance data storage capacity over the next few years.
Coping with chromosomal stress
Chromosomal instability (CIN) is detrimental for cellular fitness and is a hallmark of the majority of solid tumors. How cells adjust to this instability to ensure survival is poorly understood. The lab of Christopher Campbell has now studied the long-term adaptation to CIN using yeast cells. They found that cells accumulate mutations over time that help them to alleviate the negative effects of CIN. The work is published in The EMBO Journal.
Portrait of a protein family
SPOC domains are protein domains found across eukaryotes. SPOC containing proteins are associated with transcription regulation, development and differentiation. In their latest study, the lab of Dea Slade has now studied all known SPOC containing human proteins. They discovered that the SPOC domain is universally able to read phosphorylation marks in the C-terminal domain of RNA polymerase II, but that subfamilies of SPOC proteins recognize different patterns of CTD marks and bind to additional proteins. The study is published in Nature Communications.
Punching holes in the nucleus
Nuclear pore complexes (NPCs) are the gateways between the nucleus and the cytoplasm. How the individual components assemble into a functional pore is not understood. In a new study, published in Nature, Max Perutz Labs group leader Shotaro Otsuka and the lab of Jan Ellenberg (European Molecular Biology Laboratory, EMBL) provide the first step-by-step guide to NPC assembly. In the future, their approach could be applied to investigate the assembly mechanisms of other molecular machines in the cell.
New funding for Max Perutz Labs scientists
The Austrian Science Fund FWF has allocated €2 million in funding to a joint doc.funds initiative coordinated by Javier Martinez. The course will provide training to doctoral students in RNA biology and includes scientists from the Max Perutz Labs, the Institute of Molecular Biotechnology (IMBA), the Research Institute of Molecular Pathology (IMP), the Gregor Mendel Institute (GMI), and the Medical University of Vienna. Congratulations also to Sebastian Falk, who is part of a Weave Cross Border project and Gijs Versteeg, who has been awarded a stand-alone project grant.
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