Quickscan - End of 2018

8 January 2019

#AD&FTD Mutation Database #Data mining #Progranulin
The online AD&FTD Mutation Database was conceived by the Christine Van Broeckhoven lab (VIB–UAntwerp Center for Molecular Neurology) and currently provides curated, referenced information of 764 genetic variants associated with monogenic forms of Alzheimer’s disease (AD) and frontotemporal dementia (FTD). In addition, the database stores demographic and clinicogenetic data of 1,646 dementia families associated with these mutations. In FTD, the granulin gene (GRN) has the highest number of different mutations (34%) and the second-highest number of associated FTD families after C9orf72.
Cruts & Van Broeckhoven, Methods in Molecular Biology 2018

#Endoreplication #Root development #Computational biology
Many plants undergo endoreplication, an alternative cell cycle resulting in polyploidy. In a joint effort the labs of Lieven De Veylder and Steven Maere (VIB-UGent Center for Plant Systems Biology) computationally predicted and experimentally verified the DNA ploidy level of all cells in the complete Arabidopsis root tip, revealing that endoreplication is spatiotemporally regulated, stress responsive, and likely important in coordinating cell expansion with structural stability.
Bhosale et al., Plant Cell 2018

#Mutations #Mouse #C57BL/6J
The lab of Claude Libert (VIB-UGent Center for Inflammation Research) has generated a searchable database (mousepost.be) unlocking all sequence polymorphisms of all protein-coding genes of all 36 sequenced mouse inbred lines, as compared to the reference genome of C57BL/6J (Timmermans et al., PNAS 2017). But the reference genome is not perfect. They have now provided an overview of ‘errors’ and their impact on protein function in the reference genome itself. Important defects were found, some explaining typical C57BL/6J
phenotypes. These errors could be of importance for scientists using C57BL/6J mice, and people could consider correcting some of them.
Timmermans & Libert, JCI Insight 2018
Timmermans & Libert, Trends Genetics 2018


#Mumps #Outbreaks #Vaccine failure
Recently, new mumps outbreaks have occurred in highly vaccinated populations, including in Belgium in 2012. A possible explanation could be an antigenic mismatch between the vaccine and wild-type mumps virus. Tessa Vermeire of the Lennart Martens Lab (VIB-UGent Center for Medical Biotechnology) studied the surface HN and F proteins of the mumps virus. Scop3D was used for visualization and to map amino acid changes and important functional regions on the protein structures. Differences were mainly found in HN, with eight differences in five B-cell epitopes between vaccine and wild type virus. This could lead to a decreased recognition of the wild type virus by vaccine-induced antibodies.
Vermeire et al. Scientific Reports 2018

#Candida albicans #Protein-protein interaction
The group of Patrick Van Dijck (VIB-KU Leuven Center for Microbioloy) is involved in the transfer of a complete ORFeome collection of Candida albicans genes in specific two hybrid vectors for C. albicans. They already provided a proof of concept. C. albicans translates CUG mostly in serine instead of leucine which means the classical yeast two-hybrid cannot be used. The team then performed a genome-wide mating based protein-protein interaction (PPI) which may later on result in a complete PPI map of all proteins, but more interestingly, they can screen for small compound inhibitors of PPIs that are important for the virulence of this human fungal pathogen.
Schoeters et al., mSphere 2018

#Monocyte #Inflammation #Single cell sequencing
Novel experimental approaches such as fate-mapping and single-cell sequencing have thoroughly redefined
the monocyte field. Monocytes are now known to consist of multiple subsets generated through distinct
developmental pathways with diverse functional specializations in healthy and inflamed tissues. Martin
Guilliams (VIB-UGent Center for Inflammation Research), Simon Yona (University College London) and Alexander Mildner (Max Delbrück Center for Molecular Medicine, Berlin) highlight how novel concepts in monocyte heterogeneity, emergency monopoiesis and trained immunity are bringing exciting new perspectives to monocyte research in a review article published in Immunity.
Guilliams, Mildner, Yona et al., Immunity 2018

#Plant-specialized metabolism #Transcriptional regulation #Anti-cancer compounds
The medicinal plant Catharanthus roseus produces specialized metabolites of the monoterpenoid indole
alkaloid class, including the anti-cancer compounds vinblastine and vincristine. The Alain Goossens Lab
(VIB-UGent Center for Plant Systems Biology) recently discovered a combinatorial module of transcription
factors that boosts the production of these bioactive compounds. The findings pave the way towards metabolic engineering programs for the production of these anticancer compounds in C. roseus plants.
Schweizer et al., Metabolic Engineering 2018

#CR4-NOT #Tumor #Eye cancer
CNOT3 is a protein involved in mRNA degradation and recurrently mutated in T-cell acute lymphoblastic
leukemia (T-ALL). The lab of Jan Cools (VIB-KU Leuven Center for Cancer Biology) has now shown that CNOT3 and the entire CCR4-NOT complex act as a tumor suppressor in a fruit fly eye cancer model.
Mechanistically, this could be linked to regulation of the stability of transcripts involved in DNA replication and ribosome biogenesis.
Vicente et al., Journal of Hematology & Oncology 2018

#Metastasis #Metabolic #Cancer cells
Metastasis to distant organs is a predictor of poor prognosis. Therefore, it is of paramount importance to understand the mechanisms that impinge on the different steps of the metastatic cascade. Recent work
of Elia Lacchini and Ginevra Doglioni of the Sarah-Maria Fendt Lab (VIB-KU Leuven Center for Cancer Biology) has revealed that metabolic rewiring is a hallmark of cancer cells that transition through the metastatic cascade. Their results provide mechanistic concepts concerning how metabolic rewiring supports the ability of cancer cells to undergo metastasis formation.
Elia et al., Trends Cell Biology 2018

#Early-onset dementia #Genetic testing #Clinical diagnosis
Patients suffering from early-onset dementia (EOD) are often excluded from genetic research studies because they lack a clear clinical diagnosis of a specific dementia subtype. The lab of Christine Van Broeckhoven
(VIB–UAntwerp Center for Molecular Neurology) has investigated a group of EOD patients from a larger
prospective study of dementia in Flanders by screening the known causal genes of dementia. Multiple known
pathogenic mutations have been found in this patient group. These findings suggest that genetic screening of
patients with an unclear phenotype can both improve our understanding of disease etiology and help in formulating a genetically based diagnosis.
Perrone et al., Neurobiology of Aging 2018

#Immunotherapy #mRNA coding #Tumor #Metastases
It is now clear that successful treatment of cancer will require the induction of anti-tumor immunity in addition to killing tumor cells. By inducing immunogenic cell death in tumor cells, the dying tumor cells can be recognized by antigen-presenting cells and become their own vaccine. The Xavier Saelens lab (VIB-UGent Center for Medical Biotechnology) found that direct intra-tumor delivery of mRNA encoding the mixed lineage kinase domain-like (MLKL) protein, an executioner of necroptosis, results in a systemic cellular anti-tumor immune response that can eliminate the treated tumor as well as distal nontreated tumors.
Van Hoecke et al., Nature Communications 2018

#GWAS #Adaptive immune system
While scientists have studied the links between genetic variations and a whole range of different diseases, the
characterization of this genotype-phenotype relationship for the immune system itself has received far less
attention. In a collaboration with An Goris (KU Leuven), the team of Adrian Liston (VIB-KU Leuven Center for
Brain & Disease Research) undertook a large genomewide association study to probe more than 10 million
genetic variations for links to 54 different traits relevant to adaptive immunity. They found eight previously unknown associations, all providing important biological insights into what drives variation in our immune systems.
Lagou et al., Cell Reports 2018

#Flavor production #Yeast
Flavor compounds are important for the pleasant taste of alcoholic beverages. The yeast Saccharomyces
cerevisiae is a major producer of flavor compounds in alcoholic fermentations. In beer, yeast contributes to
more than 80% of the flavor. The genetic basis of yeast flavor production is only partially understood. Research by Sylvester Holt in the group of Johan Thevelein (VIB-KU Leuven Center for Microbiology), on polygenic analysis of ethyl acetate production, a compound with a solventlike flavor, using a strain lacking already-known enzymes, revealed a new enzyme in ethyl acetate biosynthesis. Mutant alleles identified in this way can be used for cisgenic genome editing of production yeast strains.
Holt et al., MBio. 2018

#Falcon #Real-time decoding
Researchers from the lab of Fabian Kloosterman (NERF, VIB-KU Leuven-imec) have developed a new software framework to measure and interpret the replay activity of hippocampal neurons in real time. The brain-computer interface—aptly named Falcon, after the fastest moving creature on earth—was validated in an experimental setup with freely moving rats, analyzing the activity of spatial neuronal firing patterns. Because Falcon measures in real time, the system allows for the selective manipulation of specific neuronal firing sequences at a millisecond timescale, a game-changer for studies on memory and other complex brain processes.
Ciliberti et al., eLife 2018



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