Toxoplasmosis rids its host of all fear

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Toxoplasma gondii is a neurotropic parasite that infects all warm-blooded animals, including humans. Its objective is to reach the intestines of felids, the definitive host in which it reproduces sexually. To do so, the parasite first infects mice and drastically alters their behaviour. The natural aversion of mice toward cats is decreased – a phenomenon called fatal attraction – making them easy preys.

Using a set of complementary behavioral tests, Ivan Rodriguez and Dominique Soldati-Favre groups showed that T. gondii lowers general anxiety in infected mice, increases explorative behaviors, and surprisingly alters predator aversion without selectivity toward felids.

Their findings refute the myth of a selective loss of cat fear in T. gondii-infected mice and point toward widespread immune-related alterations of behaviors.

The study was published in Cell Reports on January 14, 2020.

Article

A novel protease contributes to the repair of DNA-protein crosslinks

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DNA-protein crosslinks (DPCs) are formed in the course of normal cell metabolism. However, their prolonged persistence can be extremely toxic, cause genome instability and promote diseases such as cancer.

The Stutz laboratory, together with the Kornmann (University of Oxford) and Loewith groups,describes a new mechanism required for the efficient DPC disassembly. Through a yeast genetic screen, Serbyn and collaborators identified the enigmatic Ddi1 protease as a new candidate degrading the protein moiety of DPCs. The authors show that Ddi1 helps to resolve a broad variety of DNA-protein crosslinks and functions independently of the known pathways involved in proteolytic DPC elimination.

Loss of Ddi1 sensitizes cells to several compounds that trap DPCs, including approved anti-cancer drugs. The latter provides novel insights into the putative mechanisms of drug resistance often observed in therapeutics.

The study was published in Molecular Cell on January 2, 2020.

Article

The elephant’s trunk will inspire a revolutionary robot

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An international team, including the group of Professor Michel Milinkovitch, will analyse the African elephant’s trunk, and its exceptional agility and versatility, to create a new generation of manipulative robots capable of operating in unstable environments, adapting quickly to unexpected situations and performing a multitude of concrete tasks.

Read the press release

Topoisomerases promote replication fork pausing at proteinaceous barriers

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Living organisms have to faithfully duplicate all the DNA in their chromosomes once and only once during every cell division. Replication forks pause/slow/arrest/stall during progression through chromosomes at certain tight DNA/protein complexes known as Replication Fork Barriers (RFB).  This pausing is promoted by the Fork Pausing Complex (FPC, composed of the Tof1 and Csm3 proteins in budding yeast) and opposed by Rrm3 helicase, a motor-like protein believed to displace obstacles.

Maksym Shyian and collaborators in the Shore laboratory have now discovered that the Tof1-Csm3 complex promotes fork pausing independently of Rrm3 helicase, in contrast to an old model. Instead the Fork Pausing Complex was found to mediate topoisomerase I (Top1) association with the replisome, which, together with Top2, is essential for fork slowdown (replisome sTOP mechanism).

The study was published in Genes & Development on December 5, 2019.

Article

Preprint

Plant phosphate homeostasis is regulated by an inositol pyrophosphate signaling molecule

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Phosphorus is an essential building block for nucleic acids and membranes, forms an important energy currency of the cell and can act as a signaling molecule. Soil-living organisms take up phosphorus in the form of inorganic phosphate. How cells ‘measure’ phosphate concentrations to maintain sufficient phosphate levels in their cells and tissues is poorly understood. The group of Michael Hothorn has now elucidated that phosphate homeostasis in plants is regulated by an inositol pyrophosphate signaling molecule, which is generated by a bifunctional kinase/phosphatase enzyme in response to changing ATP and phosphate levels. The signaling molecule then binds to a cellular receptor, which in turn inactivates a transcription factor regulating phosphate starvation responses. Thus, a signaling molecule relays the nutrient status of the plant to a signaling cascade, allowing for nutrient uptake, storage and redistribution. The groups of Dorothea Fiedler (Leibniz Institute for Molecular Pharmacology, Berlin, Germany), Alisdair Fernie (Max Planck Institute for Molecular Plant Physiology, Golm, Germany) and Gabriel Schaaf (University of Bonn, Germany) contributed to this study that was published in eLife on August 22.

Pushing and pulling nucleosomes to control transcription initiation

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Chromatin remodelers are protein machines that move or eject nucleosomes from the chromatin template to regulate gene expression. Kubik et al. show how two distinct classes of remodelers, which they call « pushers » and « pullers », interact genome-wide at promoter regions to determine both the frequency of gene transcription and the precise site of initiation.

Michel Milinkovitch and Robbie Loewith receive an ERC Advanced Grant

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After receiving an ERC Starting Grant in 2008 and an ERC Consolidator Grant in 2014, Robbie Loewith has been awarded an ERC Advanced Grant for his research project entitled “Tension of ENDOmembranes maintained by TORC1 (TENDO)”. The aim is to understand how TORC1 regulates, and is regulated by, vacuolar membrane tension.

The grant is endowed with 2.25 million Euros over 5 years.

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An ERC Advanced Grant has been awarded to Michel Milinkovitch for his research project entitled “Identifying how Evolution exploits physical properties of tissues to generate the complexity and diversity of Life (EVOMORPHYS)”. The aim is to identify the drivers of Life’s morphological complexity and diversity.

The grant is endowed with 2.5 million Euros over 5 years.

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Summary of the research projects

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Details (pdf)