Recent publications
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CIG-DNF joint seminar: Prof. Frank Kooy, DNF Aud., Bugnon 7-9, Jan. 28, 2020

Abstract: Many pathways have been involved in pathophysiology of the fragile X syndrome, one of the more frequent genetic causes of intellectual disability and autism. This review highlights the recent insights in the role the abnormalities in the GABAergic system play in the disorder. Since the initial observations made that the expression of specific subunits of the GABA(A) receptor were underexpressed in the fragile X knockout mouse model more than a decade ago, evidence has accumulated that the expression of approximately half of the GABAergic system is compromised in multiple species, including in fragile X patients. Functional consequences of the GABAergic deficiencies could be measured using whole-cell voltage clamp recordings. In an in vitro model of  cortical microcircuitry we observed that the loss of FMRP largely affected the electrophysiological   correlates  of  network  development  and  maturation  but  caused  less  alterations  in  single  –  cell   phenotypes Pharmalogical treatment with agonist of the receptor was been able to restore several behavioral deficits in the fragile X mouse model, including seizures, marble burying and, in part, prepulse inhibition. Trials in patients with the same agonist have demonstrated encouraging post-hoc results in the most severely affected patients, although no effect could be demonstrated in the patient group as a whole.. In conclusion, there can be little doubt that the GABAergic system is compromised in the fragile X syndrome, but also in other neurodevelopmental disorders,  and that these abnormalities contribute to the clinical abnormalities observed.

 

You can access the DNF using public transportation. If you arrive by car, as we have no available parking places on site (Bugnon 7-9), please find a parking place at the Hospital parking or in a blue parking zone along the road.

 

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Bioinformatics.: co-auth.: group Fajas

 2020 Jan 10. pii: btz858. doi: 10.1093/bioinformatics/btz858. [Epub ahead of print]

PamgeneAnalyzeR: open and reproducible pipeline for kinase profiling.

Protein phosphorylation – catalyzed by protein kinases – is the most common post-translational modification. It increases the functional diversity of the proteome and influences various aspects of normal physiology and can be altered in disease states. High throughput profiling of kinases is becoming an essential experimental approach to investigate their activity and this can be achieved using technologies such as PamChip® arrays provided by PamGene for kinase activity measurement. Here we present “pamgeneAnalyzeR”, an R package developed as an alternative to the manual steps necessary to extract the data from PamChip® peptide microarrays images in a reproducible and robust manner. The extracted data can be directly used for downstream analysis.

AVAILABILITY AND IMPLEMENTATION:

PamgeneAnalyzeR is implemented in R and can be obtained from https://github.com/amelbek/pamgeneAnalyzeR.

PMID: 31922550

 

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Clin Investig Arterioscler.: co-auth.: W.Wahli

 2019 May – Jun;31(3):111-118. doi: 10.1016/j.arteri.2019.01.004. Epub 2019 Apr 13.

Pharmacological PPARβ/δ activation upregulates VLDLR in hepatocytes.

[Article in English, Spanish]

Abstract

The very low-density lipoprotein receptor (VLDLR) plays an important function in the control of serum triglycerides and in the development of non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the role of peroxisome proliferator-activated receptor (PPAR)β/δ activation in hepatic VLDLR regulation. Treatment of mice fed a high-fat diet with the PPARβ/δ agonist GW501516 increased the hepatic expression of Vldlr. Similarly, exposure of human Huh-7 hepatocytes to GW501516 increased the expression of VLDLR and triglyceride accumulation, the latter being prevented by VLDLR knockdown. Finally, treatment with another PPARβ/δ agonist increased VLDLR levels in the liver of wild-type mice, but not PPARβ/δ-deficient mice, confirming the regulation of hepatic VLDLR by this nuclear receptor. Our results suggest that upregulation of hepatic VLDLR by PPARβ/δ agonists might contribute to the hypolipidemic effect of these drugs by increasing lipoprotein delivery to the liver. Overall, these findings provide new effects by which PPARβ/δ regulate VLDLR levels and may influence serum triglyceride levels and NAFLD development.

KEYWORDS:

EHGNA; NAFLD; PPAR; VLDLR

PMID: 30987865

 

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PLoS One.: auth.: group Herr

 2020 Jan 6;15(1):e0224646. doi: 10.1371/journal.pone.0224646. eCollection 2020.

THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation.

Abstract

Twelve human THAP proteins share the THAP domain, an evolutionary conserved zinc-finger DNA-binding domain. Studies of different THAP proteins have indicated roles in gene transcription, cell proliferation and development. We have analyzed this protein family, focusing on THAP7 and THAP11. We show that human THAP proteins possess differing homo- and heterodimer formation properties and interaction abilities with the transcriptional co-regulator HCF-1. HEK-293 cells lacking THAP7 were viable but proliferated more slowly. In contrast, HEK-293 cells were very sensitive to THAP11 alteration. Nevertheless, HEK-293 cells bearing a THAP11 mutation identified in a patient suffering from cobalamin disorder (THAP11F80L) were viable although proliferated more slowly. Cobalamin disorder is an inborn vitamin deficiency characterized by neurodevelopmental abnormalities, most often owing to biallelic mutations in the MMACHC gene, whose gene product MMACHC is a key enzyme in the cobalamin (vitamin B12) metabolic pathway. We show that THAP11F80L selectively affected promoter binding by THAP11, having more deleterious effects on a subset of THAP11 targets, and resulting in altered patterns of gene expression. In particular, THAP11F80L exhibited a strong effect on association with the MMACHC promoter and led to a decrease in MMACHC gene transcription, suggesting that the THAP11F80L mutation is directly responsible for the observed cobalamin disorder.

PMID: 31905202
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Cell Microbiol.: co-auth.: GTF

 2020 Jan 8:e13156. doi: 10.1111/cmi.13156. [Epub ahead of print]

Blind killing of both male and female Drosophila embryos by a natural variant of the endosymbiotic bacterium Spiroplasma poulsonii.

Abstract

Spiroplasma poulsonii is a vertically transmitted endosymbiont of Drosophila melanogaster that causes male-killing, that is the death of infected male embryos during embryogenesis. Here we report a natural variant of S. poulsonii that is efficiently vertically transmitted yet does not selectively kill males, but kills rather a subset of all embryos regardless of their sex, a phenotype we call “blind-killing”. We show that the natural plasmid of S. poulsonii has an altered structure: Spaid, the gene coding for the male-killing toxin, is deleted in the blind-killing strain, confirming its function as a male-killing factor. We then further investigate several hypotheses that could explain the sex-independent toxicity of this new strain on host embryos. As the second non-male-killing variant isolated from a male-killing original population, this new strain raises questions on how male-killing is maintained or lost in fly populations. As a natural knock-out of Spaid, which is unachievable yet by genetic engineering approaches, this variant also represents a valuable tool for further investigations on the male-killing mechanism. This article is protected by copyright. All rights reserved.

KEYWORDS:

Spiroplasma; endosymbiosis; male killing; spaid

PMID: 31912942

 

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Mon Feb 10-Tues Feb 11, 2020 – Lausanne Genomics Days 2020

Lausanne Genomics Days 2020

is an annual event sponsored by the University of Lausanne and the Conférence Universitaire de Suisse Occidentale (CUSO). This 2-day event will bring to Lausanne investigators from Europe and the United States to present and discuss the newest developments in genomics and genomic technologies and their impact on biological research.

Download the flyer

Monday & Tuesday February 10  & 11, 2020

Génopode, Aud. C

Registration

Preliminary Program (with webpage links)

 

Monday February 10th

 

09:30-10:00 Welcome and coffee in the Génopode hall

 

10:00-11:45 Translation regulation session

Session’s chaiperson

Prof. Sven Bergmann

 

Keynote presentation speaker

10:00 Prof. Tamir Tuller

Computational deciphering and modelling of novel gene expression rules encoded in the mRNA

 

Local speakers

10:45 Dr. Anneke Brümmer (Prof. Sven Bergman group)

LincRNA sequences are biased to counteract their translation

11:00 Dr. Cedric Gobet (Prof. Felix Naef lab)

Modeling ribosome dwell times and relationships with aminoacyl-tRNAs in mouse liver

11:25 Prof. David Gatfield

Transcriptome-wide sites of collided ribosomes reveal sequence determinants of translational pausing

 

11:45-13:00 Lunch in the Génopode hall

 

13:00-14:45 RNA processing session

Session’s chaiperson

Dr. Julien Marquis

 

Keynote presentation speaker

13:00 Prof. Stefan Ameres

SLAMseq – Dissecting gene regulatory mechanisms by time-resolved RNA sequencing

 

Local speakers

13:45 Dr. Flora Brozzi (Prof. Romano Regazzi lab)

RNA-tagging to unveil beta-cell/immune cell crosstalk in diabetes pathogenesis

14:05 Dr. Rodrigo Siqueira Reis (Prof. Yves Poirier lab)

Complex mRNA-antisense lncRNA interaction revealed by SHAPE-MaP

14:25 Lina Worpenberg (Prof. Jean Yves Roignant lab)

Shaping the nervous system by m6A mRNA modification

 

14:45-15:15 Coffee break in the Génopode hall

 

15:15-16:55 Gene editing session

Session’s chaiperson

Prof. Julia Santiago Cuellar

Keynote presentation speaker

15:15 Prof. Martin Jinek

Molecular mechanisms of genome editors

 

Local speakers

15:55 Dr. Robertas Ursache (Prof. Niko Geldner lab)

CRISPR and the new age of genetic analysis in Arabidopsis

16:20 Dr. Lotte Spel (Prof. Fabio Martinon lab)

Understanding molecular mechanisms in autoinflammation using CRISPR screens

 

16:45 Apéro in the Génopode hall

 

Tuesday February 11th

09:30-10:00 Welcome and coffee in the Génopode hall

 

10:00-11:45 Microbiome analysis session

Session’s chaiperson

Prof. Philipp Engel

 

Keynote presentation speaker

10:00 Prof. Colin Hill

A voyage through the gut virome

 

Local speakers

10:45 Dr. Kirsten Ellegaard (Prof. Philipp Engel lab)

Getting quantitative on the Microbiome: vast differences in strain-level diversity among host-associated bacterial communities

11:05 Paddy Gibson (Prof. Jan-Willem Veening lab)

Deciphering the origins of amoxicillin resistance in Streptococcus pneumoniae through experimental evolution and NGS

11:25 Prof. Guillem Salazar Guiral

Disentangling the effects of gene expression changes and community turnover in the global ocean

 

11:45-13:30 Lunch in the Génopode hall

 

13:30-15:15 Evolution Session

Session’s chaiperson

Prof. Tanja Schwander

 

Local speakers

13:30 Prof. Anne Roulin

Transposable element evolution in small genomes What can we learn from population genomics in B. distachyon?

13:50 Jelisaveta Djordjevic

Sexual conflict and the ontogeny of sex-biased gene expression in stick insects

14:10 Tom Kay

Position in the social network is a central driver of behavior and gene expression in ants

 

Keynote presentation speaker

14:30 Prof Detlev Arendt

Evolution of neurons and of the nervous system