A new hope for a therapy against retinitis pigmentosa

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Retinitis pigmentosa, a degenerative genetic disease of the eye, is characterized by progressive vision loss, usually leading to blindness. In some patients, structural defects in the photoreceptor cells have been observed, but the molecular mechanisms involved are not understood. The group of Virginie Hamel and Paul Guichard, in collaboration with the University of Lausanne (UNIL), has identified the essential role played by a molecular zipper formed by four proteins. The absence of this zipper leads to cell death in retinal cells. This discovery could lead to the development of therapeutic approaches for retinitis pigmentosa.

This article was published in the journal PLOS Biology on June 16, 2022.

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Olfactory neurons adapt to the surrounding environment

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Cross-section of the nasal cavity of a mouse (wide view). Within the dense population of olfactory neurons (in blue), the olfactory neurons expressing a specific type of receptor (Olfr151) are marked in bright green. © Madlaina Boillat

Olfactory receptors, present on the surface of sensory neurons in the nasal cavity, recognize odorant molecules and relay this information to the brain. How do these neurons manage to detect a large variability of signals and adapt to different levels of stimulation? Ivan Rodriguez‘s and Alan Carleton‘s groups investigated the gene expression profile of these neurons in the presence or absence of odorant stimulation. The scientists discovered an unsuspected variability in these profiles depending on the expressed olfactory receptor and previous exposure to odors. These results highlight a wide range of identities of olfactory neurons, and their adaptation to the surrounding environment.

The article was published in the journal Nature Communications on May 25, 2022.

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Antisense-mediated repression of SAGA-dependent genes involves the HIR histone chaperone

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Non-coding transcription through SAGA-dependent gene promoters stimulates chromatin closing.

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. The pervasiveness of non-coding transcription might have functional consequences: many non-coding transcripts overlap with promoter regions of coding genes. This might lead to the repression of the corresponding coding gene via a mechanism of transcription interference. What are the coding genes affected by transcription interference?

The team of Françoise Stutz from the Department of Molecular and Cellular Biology proposes that the targeted coding genes belong to a specific class called SAGA-dependent genes. These genes, representing 15% of coding genes, show a closed yet very dynamic chromatin at their promoter, and are more subject to expression heterogeneity in the cell population. This work reveals the importance of non-coding transcription in proper gene regulation.

This study has been performed using the baker’s yeast as a model organism. However, considering the conservation of the involved factors, it is likely that the regulation of many human coding genes may depend on the proposed mechanism.

This article was published in the journal Nucleic Acids Research on April the 27th.

Breast cancer: why metastasis spreads to the bone

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3D image showing the invasion of breast cancer cells (green) expressing ZEB1 into mouse bone tissue (red).

When cancer cells break away from a primary tumor and migrate to other organs, this is called «metastatic cancer». The organs affected by these metastases, however, depend in part on their tissue of origin. In the case of breast cancer, they usually form in the bones. In an attempt to identify what determines the organs affected by metastasis, the group of Didier Picard from the Molecular and Cellular Biology Department, in collaboration with researchers from ETH Zurich, has identified a protein involved in this phenomenon. This discovery could lead to the development of therapeutic approaches to suppress metastasis.

This article was published in the journal Nature Communications on April 19, 2022.

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Limiting energy in neurons exacerbates epilepsy

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Mitochondria (tubular structures) within the cytoskeleton filaments of neurons observed by fluorescence microscopy.

Epilepsy, one of the most common neurological disorders, is characterized by the spontaneous repetition of seizures caused by the hyperactivity of a group of neurons in the brain. Could we therefore reduce neuronal hyperactivity, and treat epilepsy, by reducing the amount of energy supplied to neurons and necessary for their proper functioning? This was tested by the group of Jean-Claude Martinou from the Molecular and Cellular Dpt in collaboration with the EPFL. The researchers discovered that, in mice, the seizures were actually exacerbated. They observed that a reduction in the amount of energy led to an increase in the level of calcium in neurons, making them hyperexcitable. These dysfunctions could be corrected when mice were fed a ketogenic diet, which is rich in lipids and has been used since antiquity.

This article was published in the journal eLife on Feb. 21, 2022.

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Paul Guichard awarded ERC Consolidator Grant

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After receiving an ERC Starting Grant in 2016, Paul Guichard, Associate Professor in the Department of Molecular and Cellular Biology, has once again been recognized for the excellence of his work with an ERC Consolidator Grant from the European Research Council, worth nearly 2.4 million euros.

This prestigious grant for researchers in the consolidation phase of their careers, awarded by the European Research Council, will support the project entitled “Integrated Structural Analysis of the Centriole (ISAC)” of the laboratory of Paul Guichard and Virginie Hamel for a period of five years.

This project aims at analyzing at both the structural and functional levels the mechanisms governing centriole assembly. To do so, they will use advanced structural proteomic approaches, hybrid techniques of cryo-microscopy, expansion microscopy, fluorescence microscopy and cell biology.

Paul’s background in brief

Paul completed a Master’s degree in Biochemistry in Paris and his PhD between 2007 and 2010 at the Institut Curie under the supervision of Sergio Marco and Anne-Marie Tassin. He then did a post-doctoral fellowship in Pierre Gönczy’s group at EPFL between 2011 and 1015. He joined the UNIGE in 2015 as Assistant Professor in the Department of Cell Biology and became Associate Professor in 2021.

He was awarded the EMBO Young Investigator in 2020 and the Friedrich Miescher Award in 2022.

A gene could prevent Parkinson’s disease

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Parkinson’s disease is a neurodegenerative disorder characterized by the destruction of a specific population of neurons: the dopaminergic neurons. The degeneration of these neurons prevents the transmission of signals controlling specific muscle movements and leads to tremors, involuntary muscle contractions or balance problems characteristic of this pathology. Emi Nagoshi‘s group form the Genetics & Evolution’s Dpt has investigated the destruction of these dopaminergic neurons using the fruit fly as study model. The scientists identified a key protein in flies, and also in mice, which plays a protective role against this disease and could be a new therapeutic target.

This article was published in the journal Nature Communications on March 17, 2022.

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Overcoming resistance to breast cancer treatment

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The combination of two drugs could overcome resistance to standard treatment.

Many breast cancer patients develop resistance to standard drug treatments aimed at preventing the growth of cancer cells. Didier Picard‘s group form the Molecular and Cellular Department has identified a molecular regulator involved in these resistance mechanisms. The loss of this regulator leads to the proliferation of cancer cells – even if they are treated – through a signaling pathway that can itself be inhibited by another treatment. The team’s findings make it possible to consider dual therapy for certain patients whose tumors no longer respond to standard treatment.

The article was published in the journal Cancers on Feb. 14th 2022.

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A mathematical secret of lizard camouflage

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The shape-shifting clouds of starling birds, the organization of neural networks or the structure of an anthill: nature is full of complex systems whose behaviors can be modeled using mathematical tools. The same is true for the labyrinthine patterns formed by the green or black scales of the ocellated lizard.  A multidisciplinary team led by Michel Milinkovitch explains, thanks to a very simple mathematical equation, the complexity of the system that generates these patterns. This discovery contributes to a better understanding of the evolution of skin color patterns: the process allows for many different locations of green and black scales but always leads to an optimal pattern for the animal survival.

The article was published in the journal Physical Review Letters on Jan. 28, 2022.

Visualizing the native cellular organization by coupling cryofixation with expansion microscopy (Cryo-ExM)

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Cryofixation has proven to be the gold standard for efficient preservation of native cell ultrastructure compared to chemical fixation, but this approach is not widely used in fluorescence microscopy owing to implementation challenges.

The Guichard-Hamel‘s group developed Cryo-ExM, a method that preserves native cellular organization by coupling cryofixation with expansion microscopy. This method bypasses artifacts associated with chemical fixation and its simplicity will contribute to its widespread use in super-resolution microscopy.

The article was published in Nature Methods on Jan. 13, 2022.