Title Promoter Affiliations Abstract "Identification of gene clusters and microbial biosynthesis of iminosugars" "Paco Hulpiau" "Researchgroup Bio-Informatics, New Mexico State University -> Department of Entomology, Plant Pathology & Weed Science, UGent -> Laboratory of Chemical Analysis (LCA), UGent -> Dep. Biotechnolgoy - Centre for Industrial Biotechnolgy and Biocatalysis (Inbio)" "The main goal of this IMINOGENE project is to develop a microbial production platform that introduces new iminosugars to the market and disrupts the current iminosugar market. The focus lies on the iminosugars themselves, which have versatile applications for various (chronic) diseases. However, the application of iminosugars is not limited to the pharmaceutical and veterinary markets but also extends to the agro-industry. Iminosugars have proven to be useful in plants' defense against certain microorganisms and predators. Furthermore, there are speculations about iminosugars serving as antioxidants or anti-inflammatory agents for food, feed, and cosmetics. The IMINOGENE project focuses on the microbial production of iminosugars. These special carbohydrates are studied in plants but rarely in terms of their microbial natural sources. Therefore, in the IMINOGENE project, the blueprints of their microbial biosynthesis are unraveled using advanced bioinformatics tools and high-throughput functionality-based screening to decipher genomic information. The latter leads to the production of these carbohydrates." "Identification of coding and non-coding cancer drivers from whole-genome re-sequencing data using gene regulatory network analysis." "Stein Aerts" "Laboratory of Computational Biology (VIB-KU Leuven), Laboratory of Molecular Biology of Leukemia (VIB-KU Leuven)" "Identification of coding and non-coding cancer drivers using gene regulatory network analysisRegulation of gene transcription is an essential process, governing complex spatio-temporal expression patterns in every living cell. Gene regulation underlies processes such as the development of embryonic stem cells into various differentiated cell types, or the reprogramming of normal cells into cancer cells. Cancer is characterized by high intra- and inter-tumor heterogeneity arising from the accumulation of protein-coding, non-coding and regulatory aberrations, mostly affecting the transcriptional program. Such heterogeneity may reflect for instance a variable response to therapy even if patients have been diagnosed with the same cancer type. This highlights the necessity to study gene regulation, to model the dysregulation in cancer which may help to identify novel targets for cancer therapy.We developed integrative methods and approaches to analyze different types of next-generation sequencing data (transcriptome, genome and epigenome) to study gene regulation in normal and cancer cells.First, we developed a human and mouse version of a computational tool i-cisTarget. This method uses motif and regulatory track enrichment analysis to detect master transcription factors (TFs) for a given set of co-expressed genes or co-regulated genomic loci. Importantly, i-cisTarget allows one to reconstruct gene regulatory networks underlying biological processes of the specific (cancer) cell types, since it provides also the TF-bound target regions that are linked to genes.Second, we combined several computational approaches, including i-cisTarget, to decode melanoma regulatory landscapes. By integrating gene expression and regulatory data, we reconstructed gene regulatory networks underlying proliferative and invasive melanoma states. Particularly, we identified MITF and SOX10 as a master regulators of a proliferative network and TEAD and AP-1 as essential regulators of an invasive network. Importantly, we found a relevant link between the invasive network and drug resistance, highlighting the potential benefit of such integrative analyses for the identification of novel therapeutic targets.Third, with the development of μ-cisTarget, we introduced a new computational approach to identify gain-of-function cis-regulatory mutations that create new “edges” in the sample-specific gene regulatory networks. This approach combines whole-genome-sequencing data with transcriptomic and/or regulatory data. This tool allowed us to predict new candidate non-coding cancer driver mutations for ten cancer cell lines for which we sequenced the transcriptome, genome and epigenome.Fourth, we performed a TF ChIP-seq meta-analysis for the genome-wide prediction of TF-binding sites. We applied this peak calling threshold-free approach on 83 publicly available TF ChIP-seq data sets representing the binding of seven different TFs. This allowed us to identify a core set of bound regions per TF that are strongly preserved across different experiments (different cell types and conditions). These sets of recurrently bound regions were further used to discover important enhancer features and to train machine learning models to predict genome-wide TF binding sites.Overall, our studies show how useful computational methods can be to resolve challenging questions in regulatory genomics. Our integrated approaches may help to better understand the rules governing oncogenic transcription, which may be relevant to the cancer therapy." "Identification of a novel gene causing frontotemporal lobar degeneration and amyotrophic lateral sclerosis through whole genome sequencing." "Ilse Gijselinck" "VIB CMN - Neurodegenerative Brain Diseases Group" "Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are lethal neurodegenerative disorders; however an appropriate therapy is not available. They belong to the same spectrum of disorders, suggesting that they share overlapping disease mechanisms. Although several genes have been identified, these do not fully explain the genetic aetiology so that other genes remain to be identified. One such gene resides at chromosome 9p13-p21 (ALSFTD2 locus), causally linked in 13 FTLD-ALS families worldwide. We also have described an FTLD-ALS family (DR14) significantly linked to the ALSFTD2 locus in which all genes were excluded, suggesting that the genetic defect resides outside the known genes or is undetectable using standard techniques. We also obtained linkage with chromosome 14q31-q32, suggesting a major modifier gene. Here, we propose to identify the genetic defect in the ALSFTD2 locus and the modifier gene at chromosome 14q. We will determine the complete genome sequence of selected patients of DR14 and follow up identified genetic variants in the linked regions. This strategy will allow for the detection of simple and complex DNA variations, maximizing the chance of identifying the genes. Characterization of these genes will contribute to the understanding of disease mechanisms for FTLD, ALS and related disorders." "NXT-EYE: integrated genomics and transcriptomics for gene identification in inherited retinal degeneration" "Inherited retinal degeneration (RD) is responsible for 5% of blindness worldwide. Geneticstudies have revealed underlying molecular defects in ~50% of individuals with RD, most ofwhich are located in the coding portion of the genome. The advent of next-generation sequencing (NGS) has revolutionized the genetic landscape. However, the massive amount ofdata produced by NGS hampers disease gene identification, requiring powerful prioritizationstrategies. In addition, there is accumulating evidence that an important fraction of genetic defects reside outside the coding regions. These are missed by genomic approaches such as exome sequencing. To overcome this, our project aims to:(i) Integrate genomics and transcriptomics NGS-based approaches, in order to uncoverboth coding and non-coding changes.(ii) Develop an extensive filtering strategy for NGS data analysis in RD, based on retinaspecific data - such as retinal expression sets of coding and non-coding RNAs andcis-regulatory mapping data of the retinal transcription factors CRX and OTX2 -combined with generic data based on homozygosity mapping.This integrated approach will be applied on 50 consanguineous families with Leber congenital amaurosis (LCA) and autosomal recessive retinitis pigmentosa (ARRP), the most severe and most common RDs, respectively. We expect that this project will push forward the limits of gene discovery in RDs, and will lead to the identification of coding and unconventional noncoding mutations in at least several new RD genes for LCA or ARRP." "Identification and characterization of gene functions involved in synergistic interactions in a pollutant degrading multi-species bacterial consortium." "Dirk Springael" "Division of Soil and Water Management, Centre of Microbial and Plant Genetics" "This project aims at determining functions at the genetic level which are important in the interactions between different bacterial members of a multispecies bacterial consortium (MBC) degrading synergistically the phenylurea herbicide linuron. The consortium consists of three bacterialstrains belonging  to three different species. Both the synergistic metabolic and physical interactions have been well-described previously. The project starts with the full-sequencing of the genomes of the three consortium members and their annotation. The identification of the inter-species signaling gene functions will be addressed by two approaches that both involve the growth of the consortium as a biofilm in continuous flow chambers. A first approach will be a differential transcription analysis of the member bacteria when grown as a consortium compared to individual biofilm growth, based on deep RNA sequencing. A second approach will involve the use of in vivo expression technology (IVET).IVET is a promoter-trapping technique that selects microbial promoters active in a specific niche which will be in this case the 3-membered consortium grown as a biofilm. The role of the identified inter-species signaling gene functions will be assessed by analyzing the effect of knocking out those genes on synergistic interactions in the MBC.  " "Gene identification in female patients with intellectual disability and skewed X-inactivation." "Guy Froyen" "Human Genome Laboratory, Department of Human Genetics" "Intellectual disability (ID), with a prevalence of 2 % in thegeneral population, is one of the leading socio-economical problems of the Western world today and yet in 40 to 60 % of cases the etiologyis still unknown. ID is often associated with aberrations on the X-chromosome (X-linked ID, XLID). Traditionally, XLID studies were focused on male patients from XLID families. Females can be carrier of a mutation but are generally not affected because of inactivation of the mutant X-chromosome in all their cells (skewing). Mutations in X-linked genes are therefore generally not searched for in female ID patients. My project however, will focus on the identification and characterization of (novel) female-specific ID genes in sporadic female ID patients, using skewing of X-inactivation as a first selection criterion for further research. This choice is based on our recent finding that the severe syndromic clinical phenotype of two females is due to unfavorable skewed X inactivation i.e. the genetic defect is located on the active X chromosome. Therefore, the masking effect caused by random X-inactivation no longer plays a role. We will first define the X-inactivation status in female ID patients. Next, DNA samples from females with skewing will be genetically analyzed with high-resolution X-oligo-array and X-exome sequencing to identify mutations that could have led to the ID. Potential causality of confirmed mutations will be subjected to functional analysis including genotype/phenotype correlation studies and tissue expression/endophenotype correlation studies. " "Identification of the major determinants that explain intolerance to gene duplication in the flowering plants" "Yves Van de Peer" "Department of Plant Biotechnology and Bioinformatics" "Genomes are dynamic entities that change over time. An important mechanism by which genomes evolve novel functions is gene and genome duplication. However, not all cellular processes are equally malleable by evolution through gene duplication. Studies in human genomes have revealed that certain genes might be intolerant to duplication, leading to human disease. Similarly, we recently discovered that many flowering plant (angiosperm) genes appear preferentially as single copy in all angiosperm genomes sequenced. This is surprising given the duplication-rich history of the angiosperms. The basis of this intolerance for duplication remains unknown. A popular hypothesis is that duplication directly influences the amount of protein that gets produced and as such disturbs key pathways in which these ‘dosage-sensitive’ genes are involved. Alternatively, putative mutations in the duplicate copy might interfere with the essential wild-type function of the corresponding single copy gene, as such promoting fast removal of duplicated copies from the genome. Here, we will leverage the availability of large collections of omics data, to pinpoint key determinants underlying intolerance to duplication. We believe that obtaining a deep understanding in a widespread evolutionary process such as gene duplication, will have wide-ranging applications from understanding the role of duplication in adaptation to understanding how it can impact plant fitness." "Identification of the gene regulatory networks controlling vascular development in plants – a comparative approach at single-cell resolution" "Klaas Vandepoele" "Department of Plant Biotechnology and Bioinformatics" "When plants colonized the land evolved specialized structures which enabled anchorage and movement of nutrients and water throughout the whole plant, the root and the vascular system. Large evolutionary changes such as this are the result of modifications of the gene regulatory network (GRN), composed of regulators controlling the expression of target genes, that controls organ development. In order to unravel the key changes which led to the evolution of vascular tissue, I will use comparative network biology and Single Cell technologies (scRNA-, scATAC-Seq) to obtain a detailed overview of the regulatory networks in different cell-types of three plant species, including non-vascular and vascular plants. By following the changes of the cell-type specific sub-networks in the different species, I will identify conservation and differences in network organization which can eventually explain morphological evolution. While the use of distantly related species will offer the possibility to unravel master regulators and new molecular players which contributed to the transition from non-vascular to vascular plants, the comprehensive datasets will provide an important resource for the whole plant community to study both gene expression and regulation at single cellular level." "Inter-species identification of gene functions in plants based on RNA expression data Seq-" "Klaas Vandepoele" "Department of Plant Biotechnology and Bioinformatics" "The abstract for ""Inter-species identification of gene functions in plants based on RNA expression data Seq-"" is missing. Please contact the promotor for more information" "Identification of the key gene of 18q deletions: human embryonic stem cells as a research model in oncogenetics" "Claudia Spits" "Department of Embryology and Genetics" "Identification of the key gene of 18q deletions: human embryonic stem cells as a research model in oncogenetics"