Recent publications

Bioinformatics.: auth.: C.Dessimoz

Bioinformatics. 2017 Aug 30. doi: 10.1093/bioinformatics/btx542. [Epub ahead of print]

Gearing up to handle the mosaic nature of life in the quest for orthologs.


The Quest for Orthologs (QfO) is an open collaboration framework for experts in comparative phylogenomics and related research areas who have an interest in highly accurate orthology predictions and their applications. We here report highlights and discussion points from the QfO meeting 2015 held in Barcelona. Achievements in recent years have established a basis to support developments for improved orthology prediction and to explore new approaches. Central to the QfO effort is proper benchmarking of methods and services, as well as design of standardized datasets and standardized formats to allow sharing and comparison of results. Simultaneously, analysis pipelines have been improved, evaluated, and adapted to handle large datasets. All this would not have occurred without the long-term collaboration of Consortium members. Meeting regularly to review and coordinate complementary activities from a broad spectrum of innovative researchers clearly benefits the community. Highlights of the meeting include addressing sources of and legitimacy of disagreements between orthology calls, the context dependency of orthology definitions, special challenges encountered when analyzing very anciently rooted orthologies, orthology in the light of whole-genome duplications, and the concept of orthologous versus paralogous relationships at different levels, including domain-level orthology. Furthermore, particular needs for different applications (e.g. plant genomics, ancient gene families, and others) and the infrastructure for making orthology inferences available (e.g. interfaces with model organism databases) were discussed, with several ongoing efforts that are expected to be reported on during the upcoming 2017 QfO meeting.

PMID: 28968857




Expert Rev Proteomics.: auth.: PAF

Expert Rev Proteomics. 2017 Oct 9. doi: 10.1080/14789450.2017.1389649. [Epub ahead of print]

Proteomic interrogation of HSP90 and insights for medical research.


Heat shock protein 90 (HSP90) regulates protein homeostasis in eukaryotes. As a “professional interactor”, HSP90 binds to and chaperones many proteins and has both housekeeping and disease-related functions but its regulation remains in part elusive. HSP90 complexes are a target for therapy, notably against cancer, and several inhibitors are currently in clinical trials. Proteomic studies have revealed the vast interaction network of HSP90 and, in doing so, the extent of cellular processes the chaperone takes part in, especially in yeast and human cells. Furthermore, small-molecule inhibitors were used to probe the global impact of its inhibition on the proteome. Areas covered: We review here recent HSP90-related interactomics and total proteome studies and their relevance for research on cancer, neurodegenerative and pathogen diseases. Expert commentary: Proteomics experiments are our best chance to identify the context-dependent global proteome of HSP90 and thus uncover and understand its disease-specific biology. However, understanding the complexity of HSP90 will require multiple complementary, quantitative approaches and novel bioinformatics to translate interactions into ordered functional networks and pathways. Developing therapies will necessitate more knowledge on HSP90 complexes and networks with disease relevance and on total proteome changes induced by their perturbation. Most work has been done in cancer, thus a lot remains to be done in the context of other diseases.


HSP90 interactome; HSP90 networks; cancer; chaperome; chaperones; epichaperome; human disease; proteomics

PMID: 28990809




Welcome to the First-Step students!

Welcome to Charline Carron and Anthony Elia (group Thorens), Julien Dénéréaz and Lucien Roesch (group Dion), as well as Marie-Pierre Meurville (group Fankhauser-Vital IT), who are joining the CIG for a period of 10 weeks, in order to pursue a research project.



Elife.: co-auth.: P.Franken

Elife. 2017 Oct 5;6. pii: e28751. doi: 10.7554/eLife.28751. [Epub ahead of print]

Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment aftersleep deprivation.


Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability aftersleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain’s coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep.


human; mouse; neuroscience

PMID: 28980941




Cell Mol Life Sci.: auth.: group Fajas

Cell Mol Life Sci. 2017 Oct 7. doi: 10.1007/s00018-017-2668-9. [Epub ahead of print]

Role of cell cycle regulators in adipose tissue and whole body energy homeostasis.


In the course of the last decades, metabolism research has demonstrated that adipose tissue is not an inactive tissue. Rather, adipocytes are key actors of whole body energy homeostasis. Numerous novel regulators of adipose tissue differentiation and function have been identified. With the constant increase of obesity and associated disorders, the interest in adipose tissue function alterations in the XXIst century has become of paramount importance. Recent data suggest that adipocyte differentiation, adipose tissue browning and mitochondrial function, lipogenesis and lipolysis are strongly modulated by the cell division machinery. This review will focus on the function of cell cycle regulators in adipocyte differentiation, adipose tissue function and whole body energy homeostasis; with particular attention in mouse studies.


Adipose tissue; CDKs; Cell cycle; Cyclins; Insulin resistance; Metabolism; Obesity

PMID: 28988292

Cell Rep.: co-auth.: W.Wahli

Cell Rep. 2017 Oct 10;21(2):403-416. doi: 10.1016/j.celrep.2017.09.065.

A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response.


While the physiological benefits of the fibroblast growth factor 21 (FGF21) hepatokine are documented in response to fasting, little information is available on Fgf21 regulation in a glucose-overload context. We report that peroxisome-proliferator-activated receptor α (PPARα), a nuclear receptor of the fasting response, is required with the carbohydrate-sensitive transcription factor carbohydrate-responsive element-binding protein (ChREBP) to balance FGF21 glucose response. Microarray analysis indicated that only a few hepatic genes respond to fasting and glucose similarly to Fgf21. Glucose-challenged Chrebp-/- mice exhibit a marked reduction in FGF21 production, a decrease that was rescued by re-expression of an active ChREBP isoform in the liver of Chrebp-/- mice. Unexpectedly, carbohydrate challenge of hepatic Pparα knockout mice also demonstrated a PPARα-dependent glucose response for Fgf21 that was associated with an increased sucrose preference. This blunted response was due to decreased Fgf21 promoter accessibility and diminished ChREBP binding onto Fgf21 carbohydrate-responsive element (ChoRE) in hepatocytes lacking PPARα. Our study reports that PPARα is required for the ChREBP-induced glucose response of FGF21.


ChREBP; FGF21; PPARα; glucose intake; sucrose preference

PMID: 29020627