Quickscan-2018-II

10 August 2018
#Natural killer cells #Allergic asthma
The Bart Lambrecht and Hamida Hammad Lab (VIB-UGent Center for Inflammation Research) focused on the role of innate natural killer (NK) cells in house dust mite-allergic asthma. They used genetically engineered Ncr1-DTA or Ncr1-DTR mice, which constitutively or temporarily lack NK cells, and showed that these mice still developed a robust and intact allergic inflammatory response. Similar results were obtained by injecting NK cell-depleting antibodies, and by interfering with the NK cell-activating receptor NKG2D. Thus, their findings comprehensively demonstrate that NK cells are not required for asthma development in mice.
Haspeslagh et al., EMBO Mol. Med. 2018

#GRN founder family #Clinical heterogeneity #Onset age modifiers #Neuropathology
The Christine Van Broeckhoven lab (VIB-UAntwerp Center for Molecular Neurology) performed a 10-year follow-up on the Flanders-Belgian GRN founder family. The GRN founder mutation reduces levels of GRN protein by 50% and leads to a high risk of frontotemporal dementia (FTD). The updated pedigree comprises 29 branches and includes 85 patients and 40 unaffected mutation carriers. Most patients were diagnosed with FTD while others were diagnosed with Alzheimer’s dementia or Parkinson’s disease. At autopsy, the brains of 11 patients showed the typical FTLD-TDP type A pathology. Patients had onset ages ranging from 45 to 80 years, with some surviving till advanced ages without symptoms. Reported modifiers could not explain the onset age variability. The availability of this well-documented GRN founder pedigree will be key in the search for the main onset age modifiers using different omics technologies. Finding such a modifier might contribute to the development of a disease-delaying therapy.
Wauters, Van Mossevelde et al., Neurobiology of Aging 2018
Sieben et al., Alzheimers Res. Ther. 2018

#Plant growth-promoting hormones #Ubiquitination #Endocytosis
Brassinosteroids, plant growth-promoting hormones, are perceived by a cell surface-localized receptor kinase, BRI1. The BRI1 signaling intensity is mainly determined by receptor abundance in the plasma membrane. A collaborative study performed by the labs of Jenny Russinova (VIB-UGent Center for Plant Systems Biology) and Libo Shan (Texas A&M University, USA) discovered that plant U-box E3 ubiquitin ligases PUB12 and PUB13 control endocytosis of BRI1 by ubiquitination, which is driven by hormone perception. This work provides a molecular link between BRI1 ubiquitination, endocytosis, signaling regulation and plant
growth control.
Zhou, Liu et al. Proc. Natl. Acad. Sci. USA 2018

#N-terminal proteoforms #Initiator methionine excision
Protein biogenesis is a fundamental and complex biological process with important implications for human health and disease. In the case of eukaryotic cytosolic protein synthesis, typically for more than half of all nascent protein chains, the initiator methionine (iMet) is cotranslationally removed by the action of methionine aminopeptidases (MetAPs). Petra Van Damme (VIB-UGent Center for Medical Biotechnology) and her team studied the omics-wide effects of human MetAP1 deletion, thereby revealing that MetAP1 is a potential target for the discovery of new anti-obesity and anticancer therapeutic strategies.
Jonckheere et al., Mol. Cell. Proteomics 2018

#Lignin engineering #Dwarfism #Bio-based economy
To ease the industrial processing of plant biomass into fermentable sugars, plants are engineered to contain less lignin. Unfortunately, this intervention typically leads to reduced yield. The Wout Boerjan Lab (VIB-UGent Center for Plant Systems Biology) has now found a way to overcome this problem. Unexpectedly, the strategy used increased the yield beyond that of wild-type plants. These findings are an important step in the development of feedstock for biofuels and other bio-based materials.
De Meester et al. Plant Physiol. 2018

#Libraries #NGS #Toolbox
The paramount role of accurate nucleic acid library construction for deep sequencing is often underappreciated. Recent years have seen an explosion of new tools and enzymatic tricks to counter biases associated with library generation, but these are often scattered across literature or hidden in methods or supplementary sections. Armed with their own experience in customizing library construction for high-throughput experiments, the Nico Callewaert Lab (VIB-UGent Center for Medical Biotechnology) reviewed the vast expanse of tools and recent developments in the field to guide researchers in building their own
high-quality libraries.
Boone et al, Nucleic Acids Res. 2018

#Proteinaggregation #Antibiotics
Aggregation is a sequence-specific process, nucleated by short aggregation-prone regions, (APRs) that can be exploited to induce aggregation of proteins. Researchers from the VIB Switch Laboratory, led by Joost Schymkowitz and Frederic Rousseau (VIB-KU Leuven Center for Brain & Disease Research), found that while most of these regions are unique within a proteome, a small minority exist in many proteins. When they
nucleate aggregation in bacteria, massive and lethal inclusion bodies are formed, indicating that targeting these redundant APRs may be an attractive antibacterial strategy.
Khodaparast et al., Nature Communications 2018

#Respiration #Thermography
Measurements of respiratory rate are essential in biomedical research and in clinical practice, but most techniques require the attachment or implantation of sensors. Infrared thermography, on the other
hand, is noninvasive, but analysis can be complex. Researchers from the Sebastian Haesler Lab (NERF)
developed a novel algorithm that extracts respiration signals based on pixel time series, eliminating the
need for nose tracking and image segmentation. The algorithm allows the reliable detection of inhalation onset with high temporal precision, both in mice and humans.
Mutlu et al. Journal of Neuroscience Methods 2018

#Atlastin-3 neuropathy mutations #ER tethering
The ER is a complex network of sheets and tubules that is continuously being remodeled. The relevance
of this membrane dynamic is underscored by the fact that mutations in atlastins (ATL), ER fusion proteins in mammals, cause neurodegeneration. Joint efforts from the Janssens Lab and Savvides Lab at VIB-UGent Center for Inflammation Research, the Timmerman Lab at VIB-UAntwerp Center for Molecular Neurology and the Bioimaging Core in Ghent have unraveled how defects in atlastin-3 disrupt neuronal homeostasis. By using volume EM in patient fibroblasts, neuronal cells and transfected cell lines, they revealed that HSAN-causing ATL3 mutants promote aberrant ER tethering hallmarked by bundles of parallel-running ER tubules. This was caused by a defect in an intermediate step in the functional cycle of the ATL3 GTPase, leading
to excessive tethering of membranes. These data reveal that the effects of ATL3 mutations on ER
network organization stretch beyond a loss of fusion, shedding new light on atlastin neuropathies.
Krols et al., Cell Reports 2018

#Frontotemporal dementia #Genetic association #Sortilin
An international group of scientists led by researchers from the Christine Van Broeckhoven Lab (VIB-UAntwerp Center for Molecular Neurology) used genetic screening of the coding region of the sortilin 1 gene (SORT1) to identify missense mutations that are associated with an increased risk for frontotemporal dementia (FTD). SORT1 is a neuronal receptor for granulin (GRN) and mutations in the latter gene are the most frequent genetic defects in Flemish FTD patients. The risk association of SORT1 missense mutations was confirmed in three FTD patient groups in Spain, Italy and Portugal, within the frame of the European Early-Onset-Dementia (EU EOD) consortium. Several mutations were located in the SORT1 binding domain of GRN. The study’s data established SORT1 as a risk factor for FTD.
Philtjens et al., Neurobiology of Aging 2018

#Molecular details # Protein crystal nucleation
A team of researchers led by Mike Sleutel (VIB-VUB Center for Structural Biology) in collaboration with scientists from the Institute for Complex Molecular Systems of the Eindhoven University of Technology and the CNRS in Grenoble, have uncovered for the first time the molecular details of protein crystal nucleation, a process with great medical and scientific relevance. The team also developed a new methodology to study a broad class of systems that have remained elusive to date.
Van Driessche et al., Nature 2018

#Hybrid sterility #Hybrid vigor
Claude Libert and Tino Hochepied from the VIB-UGent Center for Inflammation Research have collaborated with a group of geneticists in Tubingen, Germany to study genetic problems. Crossing animals of different species leads to the extreme genetics of hybrid vigor (robust resistances and fitness), but also hybrid male sterility. Tino and Claude generated embryonic stem cells from crosses of the house mouse (Mus musculus) and the Algerian mouse (Mus spretus). By modulating the Bloom gene, it has become possible to force mitotic recombination in male hybrid cells and generate mice from these cells. In this way, recombination
in these infertile male hybrids became possible via a detour, allowing genetic studies to address
hybrid vigor and sterility.
Lazzarano et al., PNAS 2018
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