Quickscan IV

7 January 2020
#ChemoProteomics #S-sulfenylation #PlantRedox #Signalling 
In plants, the full repertoire of redox switches regulating cellular signals remained largely underexplored. Now, the labs of Frank Van Breusegem (VIB-UGent Center for Plant Systems Biology), Joris Messens (VIB-VUB Center for Structural Biology), and Kris Gevaert (VIB-UGent Center for Medical Biotechnology) applied state-of-the-art chemoproteomics to intact Arabidopsis cells and reported an inventory of protein S-sulfenylated cysteine sites in plants for the first time. This is a giant leap forward and entails an important resource that is of high interest for the plant redox community and beyond.
Huang et al., PNAS 2019

#Ubiquitin #Enzyme #ImmuneCell #MTor
The ubiquitin-editing enzyme A20 is a well-known regulator of immune cell function and homeostasis. Here, the labs of Bart Lambrecht, Hamida Hammad and Sophie Janssens (VIB-UGent Center for Inflammation Research) identify a novel component in the A20-mediated decision between life and death. Unexpectedly, rapamycin, a well-established inhibitor of mTOR, strongly protected NK-A20-/- cells from death, and further studies revealed that A20 restricts mTOR activation in NK cells. This study therefore maps A20 as a crucial regulator of mTOR signaling and underscores the need for a tightly balanced mTOR pathway in NK cell homeostasis.
Vetters et al., Journal of Experimental Medicine 2019

#Inflammation #Glucocorticoidblackout #Sepsis #TranscriptionFactor
In acute inflammation and sepsis, the Glucocorticoid Receptor (GR) loses the competition with inflammatory transcription factor NFkB for the cofactor p300. By this mechanism, found by the Claude Libert lab (VIB-UGent Center for Inflammation Research), GR loses function in the liver. This is a problem because it causes numerous metabolic changes and a lack of anti-inflammatory effects of glucocorticoids. 
Dendoncker et al., PNAS 2019

#BackPain #Inflammation #Spondyloarthritis #Diagnosis
Inflammatory back pain (IBP) is considered so essential in the axial spondyloarthritis (axSpA) diagnostic process that it is recommended as referral parameter in primary care. However, axSpA patients without IBP do exist as well as patients with IBP that do not have an axSpA diagnosis. In this study, scientist from the Dirk Elewaut lab (VIB-UGent Center for Inflammation research) report on the diagnostic utility of IBP according to the ASAS criteria and the individual IBP parameters in several rheumatology settings throughout Europe. Their results suggest that the distinctive impact of IBP is almost fully expressed when physicians refer their patient to the rheumatologist
de Hooge et al., Annals of the Rheumatic Diseases 2019

#Alzheimer #Microglia #MouseModel #StemCell
Genetics highlight the central role of microglia in Alzheimer’s disease but at least 36% of AD-risk genes lack good mouse orthologues. Here, the Bart De Strooper lab (VIB-KU Leuven Center for Brain & Disease Research) shows that embryonic stem cell (ESC)-derived human microglia successfully engraft the mouse brain. Upon exposure to oligomeric Aβ, a wide range of AD-risk genes are expressed that are not readily studied in current mouse models for AD. This work provides a unique humanized animal model that will allow elucidating the role of genetic risk in the pathogenesis of AD.
Mancuso et al., Nature Neuroscience 2019

#Leukemia #Mutation #CRISPR #GeneExpression
Analysis of sequence data from 419 T-cell acute lymphoblastic leukemia (T-ALL) cases demonstrated a significant association between SUZ12 and JAK3 mutations. The Jan Cools lab (VIB-KU Leuven Center for Cancer Biology) shows that CRISPR/Cas9-mediated inactivation of Suz12 cooperates with mutant JAK3 to drive T-cell transformation and T-ALL development. Among the broad genome and gene expression changes observed upon Suz12 inactivation, the integrated analysis identified specific pathways as vulnerabilities in T-ALL cells with combined JAK3 and SUZ12 mutations.
Broux et al., Blood 2019

#ALS #MotorNeuron #Metabolism #CRISPR
Energy metabolism has been linked to amyotrophic lateral sclerosis (ALS). Yet, motor neuron (MN) metabolism remains poorly studied and it is unknown if ALS MNs differ from healthy MNs. To address this question, the Ludo Van Den Bosch lab (VIB-KU Leuven Center for Brain & Disease Research) compared MNs from ALS patients carrying FUS mutations to their CRISPR/Cas9-corrected counterparts. They show that ALS-causing mutations in FUS did not affect glycolytic or mitochondrial energy metabolism of human MNs in vitro. These data show that metabolic dysfunction is not the underlying cause of the ALS-related phenotypes previously observed in these MNs.
Vandoorne et al., Nature Communications 2019

#CharcotMarieTooth #Myelin #ExomeScreening #Neuropathy
Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder characterized by wide clinical, genetic and pathomechanistic heterogeneity. Recently, the gene encoding peripheral myelin protein 2 (PMP2) was identified as a novel cause for CMT neuropathy. The Albena Jordanova lab (VIB-UAntwerp Center for Molecular Neurology) used whole exome sequencing and cohort screening to identify two novel missense substitutions in PMP2 in Bulgarian and German families. This finding significantly expands the genetic and phenotypic spectrum of PMP2-related peripheral neuropathy. 
Palaima et al., Orphanet Journal of Rare Diseases 2019

#NeuralCircuit #BrainDevelopment #CorticalNeuron #MouseHumanChimera
How neural circuits develop in the human brain has remained almost impossible to study at the neuronal level. Here, a collaboration between the labs of Pierre Vanderhaeghen (VIB-KU Leuven Center for Brain & Disease Research) and Vincent Bonin (NERF, empowered by VIB, imec and KU Leuven) investigated human cortical neuron development, plasticity and function, using a mouse/human chimera model in which xenotransplanted human cortical pyramidal neurons integrate as single cells into the mouse cortex. Their findings provide new insights into human neuronal development, and open novel experimental avenues for the study of human neuronal function and diseases.
Linaro et al., Neuron 2019

#Probiotic #Yeast #GenomeSequencing #AceticAcid
The Johan Thevelein lab (VIB-KU Leuven Center for Microbiology) has identified a trait of the yeast Saccharomyces boulardii, sold world-wide as probiotic, that can explain its probiotic potency. The yeast accumulates unusually high amounts of acetic acid, causing strong antibacterial activity. The better-known baker’s, beer and wine yeast, Saccharomyces cerevisiae, produces negligible amounts of acetic acid. Despite their similar genome sequence, two specific mutations were identified in S. boulardii responsible for high acetic acid production, providing the first reliable genetic signature for S. boulardii.
“The genetic signature and antibacterial potency of S. boulardii will, for the first time, allow us to identify new S. boulardii strains from nature.”
Offei et al., Genome Research 2019

#AllergicAsthma #MouseModels #Sphingolipids #ORMDL3 
Since 2007, many studies revealed a close association between polymorphisms in the ORMDL3 gene locus and allergic asthma. In yeast, ORMs are well-known regulators of sphingolipid metabolism. This led to the dogma that ORMDL3 controls allergic asthma by modulating sphingolipid metabolism. Nincy Debeuf and colleagues from the groups of Bart Lambrecht, Hamida Hammad and Sophie Janssens (VIB-UGent Center for Inflammation Research) evaluated the effect of modulating Ormdl3 levels in mice by using transgenic models. No effects on cardinal features of allergic asthma were found. This cautions against an overinterpretation of GWAS studies and shows that the role of ORMDL3 in asthma is far from established.
Debeuf et al., The Journal of Allergy and Clinical Immunology 2019