Quickscan 2019

9 October 2019
#Pain #TRPA1 #Cholesterol #CellMembrane
The cation channel TRPA1 transduces a myriad of noxious chemical stimuli into pain signals and neurogenic
inflammation. Karel Talavera and colleagues in the Thomas Voets Lab (VIB-KU Leuven Center for Brain & Disease Research) found that mouse TRPA1 localizes preferably to cholesterol-rich domains of the cell membrane and that cholesterol depletion decreases the channel’s sensitivity to chemical agonists. Understanding the impact of such interactions on TRPA1 gating mechanisms helps to understand the puzzling harmacology and pathophysiology of this important ion channel.
Startek et al., elife 2019

#PeptideSignaling #Metacaspase #DAMP #PlantImmunity
As a universal process in all multicellular organisms, damaged cells send out signals to alert the surrounding
tissue during wounding. A new discovery, in collaboration with the University of Basel (Switzerland) and led by Simon Stael, a joint postdoc in the labs of Frank Van Breusegem (VIB-UGent Center for Plant Systems Biology) and Kris Gevaert (VIB-UGent Center for Medical Biotechnology), sheds light on the cleavage and release of the damage associated molecular pattern (DAMP) Pep1 peptide upon physical damage to plants. These findings contribute to the understanding of plant immunity and may be used to improve plant breeding and crop immune response.
Hander & Fernández-Fernández et al., Science 2019

#NanoporeSequencing #StructuralVariants #Sequencing #Software
Millions of small genetic variants have been identified using short read next-generation sequencing. But the majority of the structural variants which play a role in e.g. dementia and cancer are systematically missed. Wouter De Coster and colleagues from the Christine Van Broeckhoven lab (VIB-UAntwerp Center for Molecular Neurology) showed that per human genome about 27,000 structural variants can be detected using long read sequencing on the Oxford Nanopore PromethION, co-funded by VIB TechWatch. The researchers evaluated software tools and have developed a bioinformatic workflow for efficient and sensitive structural
variant calling from long read sequencing, paving the way to reveal missing genetic variation.
De Coster et al., Genome Research 2019

#Arabidopsis #Endocytosis #Clathrin #ChemicalGenetics
Through chemical genetics, researchers from the Jenny Russinova lab (VIB-UGent Center for Plant Systems Biology) identified a specific inhibitor of endocytosis in plants. This small molecule binds to clathrin, a protein that plays a major role in the formation of coated vesicles. Such compound offers a new chemical scaffold for designing even more specific and potent endocytosis blockers that can be used in different species.
Dejonghe & Sharma et al., Nature Chemical Biology 2019

#Tuberculosis #ImprovedVaccine #ChronicInfection #Mutation
The Mycobacterium bovis Bacille Calmette Guérin (BCG) vaccine shows variable efficacy in protection against adult tuberculosis (TB). Nele Festjens and Nico Callewaert (VIBUGent Center for Medical Biotechnology) show that a live attenuated TB vaccine behaves more like an acute, rapidly immune-controlled infection, rather than the protracted chronic infection caused by the current BCG vaccine. This is likely critical to yield an immune status that affords more prolonged control of a subsequent TB infection.
Festjens et al., Vaccine 2019

#BrainAnatomy #Macrophage #Microglia #SingleCell
Even a century after their discovery, brain macrophages continue to spark fascination. Hannah Van Hove, Kiavash Movahedi and colleagues at the Jo Van Ginderachter lab (VIB-VUB Center for Inflammation Research) and the Yvan Saeys lab (VIB-UGent Center for Inflammation Research) combined single-cell transcriptomics with high-dimensional cytometry, fate-mapping and microscopy to reveal the origin and diversity of brain macrophages. This showed that macrophage phenotypes strongly varied depending on their anatomical niche.
Van Hove et al., Nature Neuroscience 2019

#Alzheimer #γ-Secretase #Nicastrin #AmyloidPrecursor
γ-Secretase complexes are multimeric membrane proteases involved in a variety of physiological processes and linked to Alzheimer’s disease. The Lucía Chávez-Gutiérrez lab (VIB-KU Leuven Center for Brain & Disease Research) found that the extracellular interface between the amyloid precursor protein and Nicastrin, one of the gamma-secretase subunits, has an important role in modulating Aβ. These findings may guide future drug discovery efforts.
Petit et al., EMBO Journal 2019

#AntiviralProteins #Influenza #HematopoeticCells #VirusTransmission
Mx proteins are evolutionary conserved dynamin-like GTPases that can suppress the replication of a large number of viruses. The possible contribution of Mx proteins in protecting immune cells against virus infection is largely unknown. Jan Spitaels and colleagues from the Xavier Saelens lab (VIB-UGent Center for Medical Biotechnology) found that Mx in hematopoietic cells plays a crucial role in the control of Thogoto virus, an influenza-like virus that is transmitted by ticks.
Spitaels et al., Journal of Virology 2019

#IntrinsicStructuralDisorder #MultifunctionalProteins #ProteinAbundance #Yeast
Properties of intrinsically disordered regions (IDRs) in Saccharomyces cerevisiae have adapted to enable functional diversity while limiting interference from promiscuous interactions in the cellular environment. Results from the Tompa and Wodak labs (VIB-VUB Center for Structural Biology) reveal that the IDR content and the frequency of ‘sticky’ amino acids (AA) in IDRs decrease with increasing protein cellular concentration. This implies that the IDR content and AA composition experience negative selection as the protein concentration increases.
Macossay-Castillo et al., Journal of Molecular Biology 2019