The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation


Despite the key proposed function of Hop/Stip1/Sti1 for protein folding and maturation, it is not essential in a number of eukaryotes and bacteria lack an ortholog. Didier Picard’s group has explored why Hop is present in eukaryotes, what its critical functions are, and whether and how the eukaryotic Hsp70-Hsp90 molecular chaperone machines may function without Hop to ensure proteostasis. Their studies on the functions of Hop as a co-chaperone of the Hsp70-Hsp90 molecular chaperone machines led them to the discovery of alternative cellular strategies that ensure proper protein folding and proteostasis in human and yeast cells lacking this co-chaperone. These findings highlight the persistence of evolutionarily more ancient mechanisms in eukaryotic cells that may contribute to balance protein folding and degradation under certain conditions.

This study was published in Nature Communications on November 25th 2020.


Snakes reveal the origin of skin colours


The skin colour of vertebrates depends on chromatophores — cells found in the deep layers of the skin. The group of Athanasia Tzika in Michel Milinkovitch’s laboratory, specialists in genetic determinism and colour evolution in reptiles, is studying the wide variety of colours sported by different individuals within the corn snake species. The research demonstrates that the dull colour of the lavender variant of corn snake is caused by a mutation in the LYS gene involved in forming lysosomes, the “garbage disposal” vesicles of cells. This single mutation is enough to affect every skin colour, demonstrating that both the reflective crystals and pigments are stored in lysosome-related vesicles. The UNIGE study marks a significant step forward in our understanding of the origin of colours and patterns in the skin of vertebrates.

The article was published in PNAS on October 5th, 2020.

Press release from UNIGE.

Wildcats threatened by their domestic cousins


European wildcats, thought to be extinct 50 or so years ago in the Jura mountains, have since recolonised part of their former territory. This resurgence in an area occupied by domestic cats has gone hand-in-hand with genetic crosses between the two species. The hybridisation between wild and domesticated organisms is known to endanger the gene pool of wild species.

Mathias Currat‘s and Juan Montoya‘s groups, in collaboration with the University of Zurich and the University of Oxford, modelled the interactions between the two species to predict the future of the wildcat in the mountainous region of the Swiss Jura. The different scenarios modelled by the scientists show that within 200 to 300 years —a very short time in evolutionary terms— hybridisation will entail the irreversible genetic replacement of wildcats, making it impossible to distinguish them from their domestic cousins, as is already the case in Scotland and Hungary.

This article was published in Evolutionary Applications on Sept. 2, 2020.

Press release

This study is also covered by other media :

Le chat sauvage va tendre à disparaître selon une étude Léman Bleu Télé / Le Journal, 29.09.2020
Le chat sauvage du Jura bientôt avalé par son cousin domestique RTS La 1ère / Journal 10h / CQFD*, 30.09.2020
Le chat sauvage est menacé de disparition… RTS La 1ère / La Matinale / Journal 7h / L’invité 7.38, 30.09.2020
Sauvage contre domestique: la bataille des chats est déclarée Tribune de Genève, 30.09.2020
Le chat sauvage, victime de son cousin domestique Le Temps, 30.09.2020

Mitochondrial RNA granules are fluid condensates positioned by membrane dynamics


Mitochondria contain the genetic information and expression machinery to produce essential respiratory chain proteins. Within the mitochondrial matrix, newly synthesized RNA, RNA processing proteins and mitoribosome assembly factors form punctate sub-compartments referred to as mitochondrial RNA granules (MRGs). Despite their proposed importance in regulating gene expression, the structural and dynamic properties of MRGs remain largely unknown. EPFL biophysicist Suliana Manley’team and Jean-Claude Martinou’s group investigated the internal architecture of MRGs and found that the MRG ultrastructure consists of compacted RNA embedded within a protein cloud. They revealed that MRGs rapidly exchange components and can undergo fusion, characteristic properties of fluid condensates. Furthermore, MRGs associate with the inner mitochondrial membrane and their fusion coincides with mitochondrial remodelling. Together, these findings reveal that MRGs are nanoscale fluid compartments, which are dispersed along mitochondria via membrane dynamics.

This study was published in Nature Cell Biology on September 28th 2020.


We’re not all equal in the face of the coronavirus


Are there differences in immunity to the SARS-CoV-2 coronavirus between populations from different geographic regions? Part of the answer to this question is to be found in the genomes of these groups of people and, more specifically, in the HLA genes responsible for the adaptive immune system. These genes are special in that they often differ between individuals. Thousands of possible variants (or alleles) have been identified, and not all of them are equally effective in fighting a new virus. The frequency of these alleles varies from one population to another due to past migrations and their adaptation to different environments. Alicia Sanchez-Mazas group,  – working in collaboration with the Max Planck Institute in Jena (Germany) and the University of Adelaide (Australia) – has pinpointed the HLA variants that are potentially the most effective against seven viruses, including the new coronavirus. They have also brought to light significant differences between populations.

This article was published in HLA on May 31st, 2020.

Press release from UNIGE.


This study is also covered by other media :

Des populations inégales face au coronavirus Avis d’Expert, RTS, 11.06.2020

Les humains pas tous égaux face au coronavirus Le Temps, 11.06.2020

UNIGE: les humains pas tous égaux face au… Radio Lac, 11.06.2020

Différences d’immunité face au coronavirus / Choisir Revue Culturelle Online, 10.06.2020

Les humains pas tous égaux face au coronavirus L’, 11.06.2020

Coronavirus: les humains ne sont pas tous…, 11.06.2020

We’re not all equal in face of coronavirus MirageNewsCom / Mirage News, 11.06.2020

Our immune systems are not all equal in the… Technology Networks, 11.06.2020

A history of the medical mask and the rise of throwaway culture


What are the causes of the shortage of face masks during the COVID-19 pandemic? Research by Bruno J. Strasser of the University of Geneva and Thomas Schlich of McGill University on the origin of the medical mask answers this question from a historical perspective.

The authors show that masks were developed at the end of the 19th century to prevent surgeons from infecting their patients. But it was during the influenza pandemic of 1918-1919 that their use became widespread to protect against infectious people. All masks, made of fabric and metal, were reusable. In the 1960s, the industry developed and vigorously promoted disposable masks. Experimental studies showed that they were no more effective than reusable masks. However, they eventually replaced reusable masks, creating a dependence on a constant supply. The recent shortage of masks, with sometimes tragic consequences for medical workers, shows the cost of this historic choice.

This article was published in The Lancet, on May 22nd 2020.

On the same topic:

” L’élimination des masques réutilisables est un choix historique discutable” : Interview from Bruno Strasser in Le Monde, published on May 25th 2020.

“2020, année de la science citoyenne?” : Le grand débat with Bruno Strasser on RTS on May 25th 2020.

“Et si l’erreur c’était de vouloir des masques jetables”: Emission radio Superfail on France Culture, June 1st 2020.

The CzcCBA Efflux System Requires the CadA P-Type ATPase for Timely Expression Upon Zinc Excess in Pseudomonas aeruginosa


Zinc (Zn) is a trace element essential for life but can be toxic if present in excess. While cells have import systems to guarantee a vital Zn intracellular concentration, they also rely on export systems to avoid lethal Zn overload. In particular, the opportunistic pathogen Pseudomonas aeruginosa possesses four Zn export systems: CadA, CzcCBA, CzcD, and YiiP. In this work, Karl Perron’s group compares the importance for bacterial survival of each export system at high Zn concentrations and shows that the P-type ATPase CadA, and the efflux pump CzcCBA are the main efflux systems affecting the bacterium tolerance to Zn.

The present data show that the fast responsiveness of cadA to Zn excess is due to its transcriptional activator, CadR, which is constitutively present on its promoter and promptly activating cadA gene expression upon Zn binding. Finally, they observed an induction of cadA and czcCBA efflux systems upon phagocytosis of P. aeruginosa by macrophages, in which a toxic metal boost is discharged into the phagolysosome to intoxicate microbes. Importantly, they demonstrated that the regulatory link between induction of the CzcCBA system and the repression of the OprD porin responsible for carbapenem antibiotic resistance, is maintained in the macrophage environment.

This study was published in Frontiers in Microbiology on the 15th May 2020.


UVR8-mediated inhibition of shade avoidance involves HFR1 stabilization in Arabidopsis


Sun-loving plants perceive the proximity of potential light-competing neighboring plants as a reduction in the red:far-red ratio (R:FR), which elicits a suite of responses called the “shade avoidance syndrome” (SAS). Changes in R:FR are primarily perceived by phytochrome B (phyB), whereas UV-B perceived by UV RESISTANCE LOCUS 8 (UVR8) elicits opposing responses to provide a counterbalance to SAS, including reduced shade-induced hypocotyl and petiole elongation.

Here Roman Ulm’s group show at the genome-wide level that UVR8 broadly suppresses shade-induced gene expression. A subset of this gene regulation is dependent on the UVR8-stabilized atypical bHLH transcription regulator LONG HYPOCOTYL IN FAR-RED 1 (HFR1), which functions in part redundantly with PHYTOCHROME INTERACTING FACTOR 3-LIKE 1 (PIL1). In parallel, UVR8 signaling decreases protein levels of the key positive regulators of SAS, namely the bHLH transcription factors PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and PIF5, in a COP1-dependent but HFR1-independent manner. We propose that UV-B antagonizes SAS via two mechanisms: degradation of PIF4 and PIF5, and HFR1- and PIL1-mediated inhibition of PIF4 and PIF5 function. This work highlights the importance of typical and atypical bHLH transcription regulators for the integration of light signals from different photoreceptors and provides further mechanistic insight into the crosstalk of UVR8 signaling and SAS.

This study was published in PLOS Genetics on the 11th May 2020.


Fine chromatin-driven mechanism of transcription interference by antisense noncoding transcription


While the spotlight has been for a long time on coding transcription, it turns out that noncoding transcription is largely predominant in a eukaryotic cell. This pervasiveness of noncoding transcription might have functional consequences: many noncoding transcripts overlap with promoter regions of coding genes. This might lead to the repression of the corresponding coding gene in a mechanism named transcription interference. It was known that this mechanism involves chromatin regulation, however the precise sequence of events triggering transcription interference was not yet defined.

The laboratory of Françoise Stutz proposes a fine mechanism of transcription interference by antisense noncoding transcription. Jatinder Kaur Gill, Julien Soudet and colleagues show that the induction of antisense noncoding transcription through the promoter region of the associated coding gene results in nucleosome repositioning. This leads to a decrease of transcription initiation of the coding gene. Based on highly resolutive sequencing technics, this study also shows that some histone modifications induce a differential positioning of nucleosomes. At last, the authors conclude that 1/5 of the coding genes are regulated through a process compatible with their model.

Considering the conservation of the involved factors, it appears likely that the regulation of many human coding genes may depend on the mechanism proposed in this publication.

This study was published in Cell Reports on the 5th May 2020.