Investigation of the mechanism of the CRISPR/Cas9 bacterial defense system has revolutionized biology, triggering applications in gene editing for basic and applied research in every organism imaginable. The basis for the revolutionary application of the CRISPR-Cas9 system was developed by Emmanuelle Charpentier at the Max Perutz Labs, whose work was published in Nature and Science.
To initiate the exchange of genetic material during meiotic recombination, cells introduce double strand breaks into chromosomes with an enzyme called Spo11, which cuts the DNA. Reporting in Nature, the team of Franz Klein has discovered that approximately 20% of initiation events are actually closely positioned pairs of DSBs. The scientists mapped the resulting fragments with single nucleotide precision across the yeast genome. This precision led to the discovery that Spo11 preferentially cleaves DNA at sites of topological stress. Intriguingly, double DSBs often correspond to promoter regions. While clearly a risk to genome integrity, the creation of gaps in chromosomes may represent an evolutionary mechanism by which to reshuffle genetic control elements.
Autophagy ensures cellular health by removing harmful material from the cytoplasm. Defects in autophagy are suspected to be involved in several human diseases. During autophagy damaged or surplus material is sequestered by double membrane vesicles, called autophagosomes, which form de novo around the cargo. The factors involved in autophagosome formation are known, but how they cooperate to initiate the formation of these membranes has so far been enigmatic. In a study published in Science, the Martens lab shows how vesicles loaded with the protein Atg9 form seeds on which the autophagy machinery assembles to form the autophagosome.
RNA molecules are frequently modified with a terminal 2’,3’-cyclic phosphate group when processed in the cell. This modification influences the stability of RNA molecules and is important for pre-tRNA splicing, the unfolded protein response and the ribosome quality control (RQC) pathway. During investigations into how this modification is carried out in the cell, Javier Martinez’ group discovered a reaction that removes RNA cyclic phosphate groups in human cells. This activity was previously known only in bacteria and viruses. The enzyme catalyzing this reaction in human cells has, until now, remained enigmatic. Reporting in Science, the researchers identified an enzyme predicted to have deadenylase activity, ANGEL2, as a 2’,3’ cyclic phosphatase. The role of ANGEL2 in pre-tRNA processing and mRNA splicing during the unfolded protein response has exciting implications for the pathology of neurodegenerative diseases.
Genetic information is tightly packed in chromatin, a material consisting of DNA strands weaved around histone proteins. Enzymes that modify histones by adding or removing specific chemical marks, alter the chromatin structure and thereby the activity of a gene. A key question in biology is how these enzymes are targeted to a specific gene to turn it on or off. Reporting exciting new findings in Nature, Alwin Köhler’s group found that one of these genetic switches behaves like a liquid. In the nucleus the protein Lge1 forms liquid droplets that act as a scaffold for Bre1, a histone-modifying enzyme that is sequestered on the surface of the liquid droplets. When dispersed, Lge1 quickly fuses together like oil droplets in water. This phenomenon, known as liquid-liquid phase separation, creates molecular crucibles where the necessary enzymes for gene regulation are condensed.
Our genetic material is safeguarded by not one, but two membranes surrounding the cell nucleus. Communication between the cytoplasm and the nucleus is gated by nuclear pore complexes, which facilitate the regulated transport of molecules in and out. While the outer nuclear membrane has long been known to be metabolically active and is contiguous with the endoplasmic reticulum, the inner nuclear membrane has been regarded as a backwater of the endomembrane system. However, Max Perutz Labs scientist Alwin Köhler and his student Anete Romanauska now seek to overturn this notion. Köhler and his team have observed that the inner nuclear membrane is in fact metabolically active and have elucidated the genetic circuit for the synthesis of nuclear lipid droplets. The work, published in Cell, has implications for fat storage, gene transcription, and understanding human diseases such as congenital lipodystrophy.
Important biological processes, including feeding and reproduction, rely on accurate timing. Many organisms therefore possess internal clocks that enable them to coordinate their activities with the environment. Adaptation of the organism’s clock, or clocks, is key to survival. A team of Max Perutz Labs scientists, led by Kristin Teßmar-Raible, has identified genes relevant for this adaptation. Intriguingly, a signaling protein that is highly abundant in the brain, calcium/calmodulin-dependent kinase, appears to be the main effector of this adaptation. The results of the study, published in the journal Nature, offer a glimpse into potential molecular candidates for calibrating an organism’s internal clock.
Gene transcription is a highly dynamic process and correct export of messenger RNAs is key to the synthesis of the correct arsenal of proteins in the cytoplasm that the cell needs. Nuclear pore complexes have long been known to be the key transport routes for molecules in and out of the nucleus, but their role in gene transcription has been somewhat enigmatic. Max Perutz Labs scientist Alwin Köhler and a team of international collaborators now show that nuclear pore complexes make use of adaptor proteins to link actively transcribed regions of the genome to their export from the nucleus and translation in the cytosol. The work, published in Cell, provides the first mechanistic insight into how nuclear pore complexes communicate directly with the transcription machinery.
Most animals require muscles to feed, flee, or fight. Force generation during skeletal muscle contraction requires that actin filaments are firmly anchored in a structure called the Z-disc, an essential component of the sarcomere, which is the repeating building block of muscle fibres. An essential and major component of the Z-disc, α-actinin, is responsible for cross-linking actin filaments as well as anchoring the protein Titin, which controls sarcomere length. Mutations in α-actinin cause muscular dystrophies and cardiomyopathies. In work published in Cell, scientists at the Max Perutz Labs, led by Kristina Djinovic, have determined the three-dimensional structure of α-actinin, shedding new light on its regulation.
To survive, bacteria must adapt to changing and often stressful environments. Adaptation strategies often center on changes in gene expression, which enable the bacteria to cope with the new environment. In work published in Cell, Isabella Moll and her team at the Max Perutz Labs show that the stress-induced endoribonuclease, MazF, selectively cleaves both a subset of mRNAs and the 16S rRNA in the decoding center of the 30S subunit of the ribosome. These modified ribosomes selectively translate the leaderless mRNAs produced by MazF and thereby tune the expression of genes required for stress adaptation.
Phenotypic diversity in sexually reproducing organisms arises from the exchange of genetic material during the formation of gametes, or germ cells. In a process called meiotic recombination, the paternal and maternal chromosomes replicate, pair, and exchange parts of their DNA by forming double-strand breaks, which are later repaired. The organization of the double-strand break machinery that carries out this essential process has long been a mystery. Franz Klein and his team at the Max Perutz Labs show, in work published in Cell, that rather than visiting recombination hotspots, the DNA break machinery lurks at the chromosome axis to break DNA-sequences that come within reach.
How to do proteomics better, faster, smarter - recent developments and opportunities in mass spectrometry
Biomechanics of Muscle Morphogenesis
Control of cell fate and morphogenesis in the developing brain
Activation and regulation of plant immunity by secreted signaling peptides
Transcription start site selection is environmentally controlled to diversify the proteome in eukaryotes
How evolutionary interplay between sexes can help us define phenotypes and develop drugs
Mining for protein-protein interactions with AlphaFold: Lessons from Genome Maintenance
Probing life at the nanoscale - one molecule at a time
The Underworld of Deep-Sea Hydrothermal Vents
Epigenetic regulation of germline development
Sister chromatid cohesion is mediated by individual cohesin complexes
Capturing conformational transitions in the ubiquitin conjugation cascade
18th Microsymposium on RNA Biology
The „Microsymposium on RNA Biology“ is an international conference that brings together young scientists, junior and senior group leaders, and company representatives from all over the world to present and discuss their latest findings in the exciting field of small RNAs and beyond. The Microsymposium was founded in 2005 and has established itself as the major small RNA meeting in Europe. It is organized by the four research institutions IMBA, IMP, GMI and the Max Perutz Labs as well as by the RNA community of the Vienna BioCenter.
Parthenogenesis, cryptobiosis, and the survival in extreme environmental conditions
Ubiquitin & Friends Symposium 2024
The Ubiquitin & Friends Symposium is an annual international meeting taking place in the beautiful capital of Austria, aiming to bring together scholars from various fields studying ubiquitin/Ubl biology and protein degradation in a personal, family-like atmosphere, as suggested by the name.
The evolution and development of mollusc shells
Unraveling the Complexity of Crossover Regulation in C. elegans
Dynamics of 3D Genome Structure and Function
How superworms can help to solve our plastic waste crisis
Shaping morphogen gradients: from molecules to tissues and back
Studying stressed cells by in situ structural biology
Exploring Microbial Resilience: Unravelling Escherichia coliand#x27;s Stress Response at the Level of Protein Synthesis
Deep homology and deep diversity: Evolving genetic toolkits for making and sensing light
The evolution of cell type identity and tissue microecology at the fetal-maternal interface
Origin and diversification of gut-derived organs in chordates
Job's Dilemma for the Genome: Why Bad Things Happen to Good Chromosomes
Understanding how the DNA-loop-extruding protein complex Condensin folds a chromatinized genome into mitotic chromosomes
Striking physiology and cell biology of (marine) environmental microorganisms
Mechanisms controlling maintenance of cohesin dependent loops
Title to be announced