Highlights

During meiosis, the formation of DNA double-strand breaks by the catalytic complex SPO11/TOPOVIBL and their repair through meiotic recombination are crucial mechanisms for the precise segregation of homologous chromosomes and the formation of gametes. However, the formation of these breaks can be dangerous and lead to undesirable chromosomal rearrangements if they are not introduced at the appropriate time and repaired correctly. Therefore, the activity of the SPO11-TOPOVIBL complex is (...)

Find the September 2023 issue (in french only).

Avian influenza viruses represents a recurring threat to human health. In particular highly pathogenic zoonotic avian strains, such as the currently circulating H5N1, can adapt to infect humans with high mortality, posing a catastrophic pandemic threat. Host adaptation is necessary for efficient replication and sustained human-to-human transmission. Amongst other adaptations, efficient replication in human cells requires mutations on the surface of the viral polymerase - the machine (...)

Researchers at the Institute of Structural Biology (IBS), in collaboration with the Laboratory of Metal Chemistry and Biology (LCBM), are investigating how the immune system responds when it encounters a threat. They are studying how certain substances, known as "alarmins," communicate with the complement defense system to alert and assist in repairing damage once the threat is under control. In their work, they are focusing on HMGB1, a protein normally located in the cell nucleus. However, (...)

The order Bunyavirales includes a large number of viruses that have a segmented negative-stranded RNA genome (sNSV). Divided into 12 families, some Bunyaviruses are major human pathogens, such as Lassa virus and Crimean Congo virus. Other viruses are emerging, such as Hantaviruses, which mainly infect arthropods and rodents, but can also infect humans, causing encephalitis or haemorrhagic fevers. There are currently no drugs or vaccines available to counter these viruses. In this context, (...)

Structural biology methods have often benefited from their cryogenic version. X-ray crystallography and electron microscopy have been revolutionized by the possibility to flash cool biological samples, reducing radiation damage or better preserving the native state of the investigated macromolecules, respectively. With the development of super-resolution microscopy (nanoscopy), the question now arises of moving towards cryo-nanoscopy. The approach has already been demonstrated by several (...)

Modifications in the exposure of molecules at surface of abnormal cells, or those dying by apoptosis, ordinarily lead to their elimination by macrophages (phagocytosis). These changes are impaired in the tumor context and this can impede phagocytosis and cause resistances to therapies. Using super-resolution fluorescence microscopy, also known as nanoscopy, because it can achieve a resolution of a few nanometers, researchers of the IBS/I2SR group have studied the distribution, diffusion (...)

Single-molecule localization microscopy (SMLM) is the most popular super-resolution fluorescence imaging technique. It is also the technique providing the best resolution enhancement, therefore being most suited for integrating structural biology into the cellular context. Like all super-resolution methods, SMLM fundamentally relies on specific fluorophore photophysical properties, like photoswitching. Its limitations, however, are also largely bound to –unwanted- fluorophore photophysics. (...)

Liquid-liquid phase separation, a ubiquitous phenomenon underlying the formation of membraneless compartments, is currently revolutionizing our understanding of cell biology. Flexible molecules, such as intrinsically disordered proteins (IDPs) are essential to maintaining the liquid properties of these highly concentrated organelles. Understanding the modulation of the structural and dynamic properties of these proteins upon phase transformation is essential to understanding this ubiquitous (...)

The traditional IBS annual scientific day took place on June 13, 2023, in the auditorium of the Fédération du BTP de l’Isère. The program offerd a large overview of the Institute’s scientific news, with a variety of formats: plenary scientific presentations, duo presentations, 180s ANR presentations as well as quizz and a video about services supports. Two doctoral students, who took part in the Ma Thèse en 180s competition in 2022 and 2023, also presented their research topic, in three minutes, (...)

Pathogenic bacteria are becoming increasingly resistant to antibiotics. Alternatives must be found and validated to avoid falling back into the pre-antibiotic era. The use of bacteriophages, natural enemies of bacteria, is one of the most promising alternatives, both in agriculture/veterinary medicine and in human health. 60% of known phages consist of a capsid protecting the viral DNA and a long flexible tail, which serves to recognise the host via one or more receptor binding proteins (...)

Congratulations to the "Entry and budding of enveloped viruses group" labelled ’FRM 2023 group’ for its project "Structure and function of ESCRT-III polymers” The prestigious "FRM team" label is awarded for three years and finances innovative work in biology and health. The research program of Winfried Weissenhorn’s group aims to understand the structural and function of “endosomal sorting complexes required for transport” (ESCRT), a highly conserved membrane remodeling machinery present in all (...)

Fluorescent proteins are widely used in biological research to make all kinds of cell types or structures visible. A research team from the University of Amsterdam has developed a new bright red fluorescent protein, mScarlet3, which combines maximum brightness with fast and complete folding. They sent their creation to the Institut de Biologie Structurale in Grenoble, where structural biologist Antoine Royant mapped the molecular structure of the protein, using the European Synchrotron (...)

From Galileo Galilei and Robert Hooke in the 17th century to David Julius and Ardem Patapoutian, who won the 2021 Nobel Prize in Physiology or Medicine, stiffness and elasticity have been a cornerstone of classical physics and now in biology. To characterize a mechanical role in biology, one task is to quantify the elasticity of a sample. In common terms, the elasticity of a material is characterized by measuring its stiffness, or the resistance of an object to the deformation under an (...)

HSP90 is a fundamental chaperone protein for many cellular processes. Through its involvement in the folding of many oncoproteins, it is a therapeutic target against cancer. HSP90 is affected by complex structural rearrangements associated with ATP binding and hydrolysis during its functional cycle. However, these structural rearrangements remain poorly described for the apo protein. In this study, researchers from IBS and ILM-Lyon have, for the first time, identified a metastable excited (...)

The C-type lectin receptor DC-SIGN has been highlighted as co-receptor for the spike protein of the SARS-CoV-2 virus. A multivalent glycomimetic ligand, Polyman26, has been found to inhibit DC-SIGN-dependent trans-infection of SARS-CoV-2. The molecular details underlying avidity generation in such systems remain poorly characterized. In an effort to dissect the contribution of the known multivalent effects - chelation, clustering and statistical rebinding –, researcher of the IBS in Grenoble (...)

Nucleotide excision repair (NER) is a conserved and versatile DNA repair pathway found in all domains of life that is responsible for eliminating a wide diversity of DNA lesions from the genome. These include UV-induced pyrimidine dimers, but also bulky adducts caused by smoking or chemotherapeutic agents. In bacteria, NER is initiated by the UvrA and UvrB proteins that together locate the lesion before recruiting a third factor, the dual endonuclease, UvrC, that cleaves the DNA on either (...)

What mechanisms are behind the appearance of flowers? To answer this question, a 25-year-old enigma has just been solved: The role of the UFO protein in this formation process. While its nature suggested that it destroys its partners, this protein is in fact an aid to the birth of a flower when it is coupled to the LEAFY protein. This was revealed by researchers from several Grenoble institutes* in a new study published in Nature Plants. Scientists already knew that LEAFY, by binding to (...)

Elke de Zitter (IBS/Dynamics and kinetics of molecular processes Group) has been awarded the European XFEL Young Scientist Award 2023, which aims at recognizing outstanding contributions to research at European XFEL by young researchers in the early stages of their career. This prize rewards De Zitter’s research on processing serial-crystallography data taken by the SPB/SFX instrument at European XFEL. To know (...)

The endosomal sorting complex required for transport (ESCRT) machinery catalyzes many divergent membrane-remodeling processes such as membrane repair, enveloped virus budding and cytokinesis, amongst others. Dysfunction of the ESCRT machinery is associated with a diverse set of pathologies such as cancer or neuronal deficiencies. Notably members of the ESCRT-III protein family are conserved in all kingdoms of life and have been proposed to polymerize on membranes and remodel them to the (...)