Quickscan II

4 August 2019
#Climate change #Plant growth #Thermosensing
Plant growth and flowering time are in part determined by environmental temperature. The combined expertise of the labs of Ive De Smet (VIB-UGent Center for Plant Systems Biology) and Kris Gevaert (VIB-UGent Center for Medical Biotechnology) allowed setting criteria for plant thermosensors that recognize a temperature cue and that trigger a specific response. To identify novel thermosensors structural analysis of DNA, RNA or proteins will be crucial.
Vu et al., Trends Plant Sci. 2019​

#SpatialMemory #Replay #Reward
Hippocampal neural replay patterns support learning in novel environments, but how replay contributes to the consolidation of experiences in a familiar context is unknown. Researchers led by Fabian Kloosterman (NERF, empowered by VIB-KU Leuven-imec) have now demonstrated that large rewards can selectively enhance performance during familiar but demanding spatial memory tasks. Post-learning hippocampal replay thus selectively reinforces spatial memory of highly rewarded locations in a familiar context.
Michon et al., Current Biology 2019

#Antibiotics #Persistence #Resistance
Bacterial persistence often prolongs antibiotic therapy, as it results in a subpopulation of tolerant cells that
survive treatment and potentially cause a relapse of the infection. Research by the group of Jan Michiels (VIB - KU Leuven Center for Microbiology) recently showed that the consequences of persistence reach even further, by promoting the development of genetic resistance. These findings highlight the importance of anti-persistence strategies, as these could reduce the emergence of antibiotic resistance.
Windels et al., ISME Journal 2019

#TOR kinase #Nutrient signalling #Plant growth
The target of rapamycin (TOR) kinase is an ancient metabolic sensor that orchestrates growth at the cellular,
tissue and organismal level. To elucidate how TOR functions in plants, the Functional Interactomics lab of
Geert De Jaeger (VIB-UGent Center for Plant Systems Biology) combined an extensive protein complex screen with phosphoproteomics for the proteome-wide discovery of upstream regulatory mechanisms and downstream targets, revealing both conserved as well as plant-specific TOR signalling events.
Van Leene et al., Nature Plants 2019
 
#Vaccine #Mice #Immunization
Vaccination is one of the most efficient and cost-effective disease prevention strategies. However, most vaccines are administered by needle injection, which requires trained medical staff. In collaboration with a Dutch biotech company, the group of Xavier Saelens (VIB-UGent Center for Medical Biotechnology) demonstrated that nanoporous ceramic microneedle arrays can be used to effectively deliver an influenza vaccine intradermally, which resulted in a robust, protective immune response in mice. Microneedle patches thus represent a promising, selfapplicable pain-free device to deliver vaccines.
Schepens et al., Eur J Pharm Biopharm 2019

#ErrorsofMetabolism #Nutritional therapy #Metabolomics
Congenital disorders of glycosylation (CDG) are rare genetic metabolic disorders arising from defects in how
the body processes sugar. One of the main treatments currently used is D-Galactose therapy which exerts its
beneficial effects in individuals diagnosed with a mutation in Phosphoglucomutase-1. PhD student Silvia Radenkovic and colleagues from the Metabolomics Core led by Bart Ghesquière (VIB-KU-Leuven Center for Cancer Biology), used tracer metabolomics to discover that D-Galactose rewire​s cellular metabolism and replenishes the pools of critical UDPsugars, causing a restoration of the protein glycosylation processes. These findings open new avenues for improved nutritional therapy for other individuals diagnosed with
similar defects.
Radenkovic et al., American Journal of Human Genetics 2019​

#Cistopic #Single cell #Heterogeneity
The Stein Aerts lab (VIB-KU Leuven Center for Brain & Disease Research) developed cisTopic, a probabilistic
framework that provides insight into the mechanisms underlying regulatory heterogeneity within cell populations. The team’s results show the value of topic modelling in the analysis of large-scale single-cell epigenomics data sets. It allows to jointly optimize cell clustering and enhancer categorization, to identify subpopulations of cells and co-accessible enhancers that represent shared epigenomic programs.
Stein’s response when interviewed by Nature Methods about how he felt when he realized the method worked: “Great! Now we have a topic matrix, we can cluster the cells on the topics and we can cluster the regions on the topics.”
Bravo Gonzalez-Blas et al., Nat Methods 2019

#Dementia #DPP6 #Neuronal hyperexcitability
Rita Cacace, a postdoc in the group of Christine Van Broeckhoven (VIB-UAntwerp Center for Molecular
Neurology), investigated a neurodegenerative dementia family previously linked to chromosome 7q63. She observed a genomic inversion which dislocated the coding sequence of the dipeptidyl peptidase 6 gene (DPP6) from its regulatory region causing loss of DPP6 protein. Resequencing of DPP6 in patients identified rare mutations leading to premature termination codons predicting transcript degradation. Additionally, rare coding variants were enriched in patients. Protein expression studies in autopsy brain tissue and in vitro assays, revealed variant-dependent DPP6 loss. It was shown in primary neurons of mice that loss of DPP6
causes neuronal hyperexcitability. These findings pave the way to the study of the homeostasis of neuronal firing in neurodegenerative dementia.
Cacace R et al. Acta Neuropathologica 2019
 
#DSCAM #Nuclear import #Down syndrome
Down syndrome cell adhesion molecule (DSCAM) receptors serve important neurodevelopmental functions including control of axon growth, branching, neurite self-avoidance, and neuronal cell death, but their signal transduction mechanisms remain poorly understood. The Dietmar Schmucker lab (VIB-KU Leuven Center for Brain & Disease Research) has identified a novel membrane-to-nucleus signaling mechanism by which DSCAM receptors can alter the expression of regulators of neuronal differentiation and synapse formation and function. Considering that chromosomal duplications lead to increased DSCAM expression in trisomy 21, these findings may help uncover mechanisms contributing to intellectual disability in Down syndrome.
Sachse et al., EMBO J 2019

#Morphology #Peptide #Inflammation
Candida albicans, a common fungal commensal residing mostly on mucosal surfaces, becomes a deadly pathogenin immunocompromised patients, partly as a result of its capacity to change morphology. A collaborative study performed in the labs of Andy Wullaert (VIB-UGent Center for Inflammation Research) and Patrick Van Dijck (VIB-KU Leuven Center for Microbiology) discovered that a small pore-forming
peptide only produced on hyphae of C. albicans activates the Nlrp3 inflammasome resulting in pro-inflammatory cytokine production. This work provides a molecular link between C. albicans morphogenesis, host recognition and immune response in the control of fungal infections.
Rogiers et al., mBio 2019

#Single cell #Trajectories #Benchmarking
By combining single-cell profiling and computation trajectory inference tools, it is now possible to investigate the dynamics of individual cells at an unprecedented and purely datadriven detail. The Yvan Saeys Lab (VIB-UGent Center for Inflammation Research) has done a comprehensive benchmark of 45 different methods for trajectory inference. They highlight the complementarity of tools, provide guidelines for method users, and indicate open challenges in the field. All software tools are freely available from dynverse.org.
Saelens et al., Nat Biotech 2019

#Asthma #Allergen immunotherapy #GM-CSF
Allergic asthma is caused by an aberrant immune response to airborne allergens, such as proteins derived from house dust mites (HDM). The Hamida Hammad and Bart Lambrecht Lab (VIB-UGent Center for Inflammation Research) showed in mice that prophylactic inhalation of one HDM allergen, Der p 2, completely prevented asthma development induced by the full HDM extract containing multiple allergens.
Der p 2 treatment mediated tolerance by blocking the release of lung GM-CSF, a cytokine crucial to endow dendritic cells with an allergy-promoting function. These insights might be exploited to improve allergen-specific immunotherapy.
Haspeslagh et al., J Allergy Clin Immunol 2019

#Spinal cord injury #Proprioception #Locomotion
Spinal cord injury disconnects communication between the brain and the spinal cord, but proprioceptive feedback (on the position and movement of the body) can contribute to locomotor recovery and the establishment of detour circuits. New work by Aya Takeoka (NERF, empowered by VIB-KU Leuven-imec) reveals that functional proprioceptive afferents caudal to the site of injury serve as a continued driving force
to initiate and maintain locomotor output after injury.
Takeoka & Arber, Cell Reports 2019
 
#Liquid chromatography #Machine learning #Data-driven modelling
Liquid Chromatography (LC) separates molecules based on their physicochemical properties and plays a key role in the analysis and identification of peptides and metabolites.​ Predicting how an analyte will behave in LC systems therefore eases its identification. Members of the Lennart Martens lab (VIB-UGent Center for Medical Biotechnology) investigated which machine learning algorithms and analyte feature representations are best at predicting LC separations, and found that the most commonly used model is not optimal, instead proposing a rarely used but superior alternative. They also found evidence for the usefulness of combination learning techniques for LC predictions.
Bouwmeester et al., Anal Chem 2019​



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