Research Filip Lemière

Abstract

The Center for Proteomics was founded about a decade ago as a UAntwerpen/VITO state-of-the-art mass spectrometry platform as a continuation of the former UAntwerpen CeProMa Core facility. Since 2017, the main focus of the UAntwerpen/VITO team was the use of proteomic approaches to identify biomarkers for early diagnosis of disease. Over the years, we have built up a multi-disciplinary team of lab technicians, mass spectrometry experts, biologists, biochemists, (bio)medical experts, mathematicians and (bio)-informaticians to set up good experimental designs, develop quality control tools, develop additional data analysis software, … Moreover, the close interactions we now have with clinical and academic partners (with complementary expertise and biobanks) give us access to high quality clinical samples and medical expertise. Today, we have the team's expertise, the network and the infrastructure that will help us bridge the gap between discovery, translation and clinical applications. Mass spectrometry based proteomics of biofluids and tissues is complementary to other techniques that are currently available at UAntwerpen. It has the advantage that it can detect modifications and discern various proteoforms. This is not possible with PCR based techniques and even new and promising techniques like single molecule protein sequencing have limitations compared to MS based techniques. Therefore, we make a combination of these techniques in our aim to create an as complete and accurate proteome profile as possible for (bio)medical applications. Besides proteomics, we also specialize in peptidomics, covering the analysis of naturally occurring small peptides which play important regulatory roles in all multicellular organisms and is especially relevant to study cellular interactions of the immune system. This type of analysis requires specialized technological skills, especially in terms of sample preparation, analytical techniques and data analysis. Some team members are worldwide pioneers in this field. This is the reason why several companies (J&J, MyNeo, …) collaborate with the CfP for exactly this type of expert scientific support. Thanks to investments from VITO and UAntwerpen (Hercules) we are equipped with state-of-the art mass spectrometers and hyphenated equipment that rival the best proteomics centers in Europe. Ours Tims-Tof mass spectrometer and Rapiflex maldi imager are unique in Flanders. With this proteomics and peptidomics platform, we focus on application driven research making it possible to work closer with the market than typical academic research groups do. This is a clear added value for both our University, VITO and the industrial partners.

Researcher(s)

• Promoter: Mertens Inge
• Co-promoter: Lemière Filip
• Co-promoter: Leroy Jo
• Co-promoter: Peeters Marc

Research team(s)

• Center for Oncological Research (CORE)

Project website

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Esmans Edgard
• Promoter: Lemière Filip
• Promoter: Lemière Filip
• Promoter: Sobott Frank
• Co-promoter: Lemière Filip

Research team(s)

Project type(s)

• Research Project

Abstract

The requested infrastructure (comprehensive liquid chromatograph-ion mobility-quadrupole time of flight mass spectrometer LCxLC-IM-QTOFMS) combines several state-of-the-art technologies into one platform which aims at bringing metabolomics research to the next level. As such, the infrastructure will deliver a combined five-dimension separation and detection technology, the first of its kind in Belgium. This instrument will be dedicated to metabolomics research, the science of endogenous metabolites in cells, tissues or organisms. The infrastructure will be able to optimally separate, detect and identify the very broad and complex chemical space of metabolites ranging from very polar (e.g. amino acids) to non-polar (e.g. lipids and hormones) at low nanomolar concentration range. Within UA, there is a growing need to combine the currently scattered efforts in metabolomics, an Emerging Frontline Research Domain in the UA research scene. Research ranges from drug discovery (mode of action and pharmacokinetic profiling), biomarker and toxicity studies to advanced data-analysis and systems biology approaches, but a dedicated metabolomics infrastructure to strengthen these studies is currently missing. As such, the investment in a core facility together with the gathering of nine research groups from five departments and two faculties would centralize the metabolomics research. This will position UA as a key player in the academic metabolomics research in the BeNeLux and worldwide.

Researcher(s)

• Promoter: Covaci Adrian
• Co-promoter: Augustyns Koen
• Co-promoter: Baggerman Geert
• Co-promoter: Bervoets Lieven
• Co-promoter: De Meester Ingrid
• Co-promoter: De Meyer Guido
• Co-promoter: Hermans Nina
• Co-promoter: Laukens Kris
• Co-promoter: Lemière Filip
• Co-promoter: Maes Louis
• Co-promoter: van Nuijs Alexander

Research team(s)

• Toxicological Centre

Project type(s)

• Research Project

Abstract

The functional levels of a biological system include the genome, transcriptome, proteome and metabolome, and the latter is considered as most representative of the phenotype. Tumors develop tumor-specific metabolism that endows them with more predominant proliferation, independent of tissue type, while retaining some metabolic traits of the tissue from which they originated. Exploring the cancer metabolome is considered as a promising way to reveal phenotypic changes related to cancer, and to establish specific biomarkers that may be used in screening for diagnostic and prognostic purposes. Many cancers have a higher cure rate if detected in early stages. Metabolomics is an analytical tool used in conjunction with pattern recognition approaches and bioinformatics to detect metabolites and follow their changes in biofluids or tissue. 1H-NMR spectroscopy and LCMS are the two major spectroscopic techniques used in metabolic analysis. This project focuses on colorectal cancer (CRC). It has been established that, apart from plasma, peripheral blood mononuclear cells (PBMC) may provide potential prognostic biomarkers for disease, and may constitute an excellent starting point for early CRC biomarker discovery. Therefore, the main objective of this project is the metabolomics analysis by 1H-NMR and LCMS of plasma and PBMC from diagnosed CRC patients in various stages and healthy controls, and to establish a set of early biomarkers for this cancer type.

Researcher(s)

• Promoter: Apers Sandra
• Promoter: Pieters Luc
• Co-promoter: Lemière Filip
• Co-promoter: Peeters Marc
• Co-promoter: Pieters Luc
• Fellow: Custers Deborah

Research team(s)

Project type(s)

• Research Project

Abstract

The instrument acquired in this project is a matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometer capable of mass spectrometry imaging (MSI). This technique is especially developed for the identification of biomolecules in a manner that retains cytological and histological patterning. This novel technical process, abbreviated to MALDI-MSI represents an interesting and extremely productive intersection between mass spectrometric and imaging platforms. Therefore, this grant is bridging 3 University of Antwerp CORE facilities (Center for Proteomics, Bio-Imaging lab and the Biomedical Microscopic Imaging Core). Using this MALDI-MSI platform, multiple research groups, brought together by a common interest in investigating molecular damage associated with aberrant aging mechanisms, will be able to identify a diverse range of small molecules (peptides and metabolites) as well as larger proteins directly on tissue slides, preserving the topological, histological and cytological data. This is not possible with routine proteomics and metabolomics technologies nor with advanced imaging techniques.

Researcher(s)

• Promoter: Maudsley Stuart
• Co-promoter: Baggerman Geert
• Co-promoter: Blust Ronny
• Co-promoter: Bogers John-Paul
• Co-promoter: Dewilde Sylvia
• Co-promoter: Husson Steven
• Co-promoter: Laukens Kris
• Co-promoter: Lemière Filip
• Co-promoter: Mertens Inge
• Co-promoter: Sobott Frank
• Co-promoter: Valkenborg Dirk
• Co-promoter: Van Der Linden Annemie
• Co-promoter: Van Ostade Xaveer

Research team(s)

Project type(s)

• Research Project

Abstract

Many of the functions of nucleic acids (DNA, RNA) depend on their precise 3D structure, and how they interact with proteins. If we want to understand the molecular basis of diseases or infection, we have to understand those interactions during the cell cycle and protein synthesis. The proteins that interact with nucleic acids typically play important roles in the structure and activity of the genome. In this PhD project we will work on protein assemblies that interact with nucleic acids and are involved in DNA structural and spatial organization and gene regulation. This includes analysis of the structure and composition of key cellular complexes as well as their mode of operation, with the help of native Mass Spectrometry (MS) and Ion Mobility (IM). These methods allow us to get information about the mass, charge and also about the size and shape of the molecular complexes. We will work within several international collaborations (Oxford, Bristol) which focus on Structural Maintenance of Chromosomes (SMC) proteins and their associated binding partners, which organize DNA during the cell cycle. This project also includes the development of novel methods for native MS of proteins and protein/nucleic acid complexes, and the use of modeling approaches to interpret the data and propose global structures of the assemblies. In this way, we hope to link information on genome management on a molecular level with mechanisms of inheritance and physiological adaptation.

Researcher(s)

• Promoter: Sobott Frank
• Co-promoter: Lemière Filip
• Fellow: Kotter (geb. Butterer) Annika

Research team(s)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Lemière Filip
• Co-promoter: Wijnants Marc
• Fellow: Goossens Eliane

Research team(s)

Project type(s)

• Research Project

Abstract

Organotin derivatives form a very important class of reagents in the organic synthetic chemistry. Due to the toxicity of the currently used organotin reagents, the difficult purification of the reaction products and the problem to recover and re-use the formed tin waste in a simple manner the industrial applications are hitherto limited. This project describes a simple though sustainable solution for the triple problem.

Researcher(s)

• Promoter: Maes Bert
• Co-promoter: Lemière Filip
• Co-promoter: Sobott Frank

Research team(s)

• Organic synthesis (ORSY)

Project type(s)

• Research Project

Abstract

Complex mixtures of mannosyl erythritol lipid (MEL) biosurfactants produced via fermentation will be purified and analytically characterized by liquid chromatography and mass spectrometry. The pure compounds will be screened for their activity against bacteria and fungi.

Researcher(s)

• Promoter: Lemière Filip
• Co-promoter: Wijnants Marc

Research team(s)

Project type(s)

• Research Project

Abstract

This project has two general objectives: (1) Increase the research potential of the UA by introduction of new state of the art techniques for the analysis of fragile molecular structures by using the novel ion mobility capabilities that have recently been integrated with high-mass high-resolution Q-TOF mass spetrometry ("Synapt", waters). (2) Maintain the current capacity to obtain Q-TOF data by replacing an existing system.

Researcher(s)

• Promoter: Sobott Frank
• Co-promoter: Guisez Yves
• Co-promoter: Lemière Filip
• Co-promoter: Maes Bert
• Co-promoter: Moens Luc
• Co-promoter: Tavernier Serge
• Co-promoter: Van Ostade Xaveer
• Co-promoter: Van Schil Paul
• Co-promoter: Wijnants Marc
• Co-promoter: Witters Erwin

Research team(s)

Project type(s)

• Research Project

Abstract

A fermentation based on feedstock sources from agro-food industry for the production of mannosylerythritol lipid biosurfactants (BIOMEL project) yields in a secretion of a complex blend of biomolecules with promising properties in food-, pharmaceutical, cosmetic and domestic housecare applications. The goal of this project is to define detailed protocols of standard procedures for isolation, purification, quantification and characterisation of current and novel MEL's from a complete fermentation broth.

Researcher(s)

• Promoter: Lemière Filip
• Co-principal investigator: Wijnants Marc
• Co-promoter: Covaci Adrian

Research team(s)

Project type(s)

• Research Project

Abstract

This project studies the regulation, phosphorylation and adduct formation of proteins in tumors upon melphalan treatment. LC-MS methods will be developed using a representative cell culture. An animal model (induced lung tumors) will be treated by melphalan isolated lung perfusion prior to analysis of human samples. Final goal is the selection of candidate biomarkers ((phospho-)protein, melphalan-proteinadduct, ...) with prognostic value for the treatment of lung metastases by melphalan-ILuP.

Researcher(s)

• Promoter: Lemière Filip
• Co-promoter: Van Schil Paul

Research team(s)

Project type(s)

• Research Project

Abstract

Mass spectrometry is a powerful analytical technique to elucidate the structure of molecules, like proteins. Until now a significant fraction of the data coming from MS analysis remains uninterpretable. This projects aims to apply state-of-the-art data mining techniques to a large set of mass spectra, aiming to find new relevant patterns that may point towards unknown structural modifications.

Researcher(s)

• Promoter: Goethals Bart
• Co-promoter: Laukens Kris
• Co-promoter: Lemière Filip

Research team(s)

• ADReM Data Lab (ADReM)

Project type(s)

• Research Project

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

• Promoter: Guisez Yves
• Co-promoter: Lambeir Anne-Marie
• Co-promoter: Lemière Filip
• Co-promoter: Maes Bert
• Co-promoter: Maes Louis
• Co-promoter: Moens Luc
• Co-promoter: Van Ostade Xaveer

Research team(s)

• Integrated Molecular Plant Physiology Research (IMPRES)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the Federal Public Service. UA provides the Federal Public Service research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Bervoets Lieven
• Promoter: De Coen Wim
• Co-promoter: Bols Peter
• Co-promoter: Lemière Filip
• Co-promoter: Maes Bert
• Co-promoter: Robbens Johan

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Lemière Filip
• Fellow: Smits Koen

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Lemière Filip
• Fellow: Henderickx Kim

Research team(s)

Project type(s)

• Research Project

Abstract

A: Urinary nucleosides It is known that some modified nucleosides originating from RNA degradation are excreted in abnormal levels in the urine of patients with malignant tumours and they have been proposed as tumour markers. Their measurement could provide a non-invasive diagnostic method, helpful for the identification of different cancers and in the monitoring of therapeutic effects. In this work the development of a fast on-line multi-column HPLC-ESMS(/MS) system for the selective sample clean up, preconcentration and subsequent analysis of the major and minor (modified) ribonucleosides in human urine will be the main objective. The high sensitivity and selectivity of miniaturised LC-MS(/MS) methods will provide us the means to isolate and detect unknown nucleosides. For the structure elucidation of those compounds MS/MS spectra will be generated and subsequently interpreted. If necessary further (spectroscopic) steps will be undertaken to offer assurance about the proposed structures. As the proposed analytical method tolerates direct administration of urine samples, it opens the opportunity for a relatively fast screening of samples. So we will use the method to generate urinary nucleoside patterns of both healthy volunteers and cancerpatients. Those patterns will be evaluated in order to discriminate, based on nucleoside concentrations, between healthy men and those suffering from ovarian, prostate or abdominal cancer. B: nucleotides A lot of nucleoside-analogues, which are intracellular metabolized to active nucleotide-analogues, are used as antiviral and cytostatic therapeutics. Therefore higher demands are placed on the technology for the analysis of nucleotides. In addition to this it may be necessary for studies of cell metabolism to separate, determine and quantify mixtures of nucleoside mono-, di- and triphosphates. A lot of chromatographic procedures for the analysis of nucleotides -all based on UV or radiometric detection- were developed in the past. However in order to acquire highly selective structural information the development of a sensitive HPLC-MS(/MS) system is required. Due to the incompatibility of mass spectrometry with the originally proposed separation methods, the development of new LC-MS compatible separations was warranted. Ion-suppression HPLC (-) ESMS and ion-pair HPLC (-) ESMS have been used for the analysis of selected analytes. Yet, a more universally applicable analytical procedure would be useful for future studies concerning the purity and biochemical/medical behaviour of nucleotide-analogues. Special concern will go to a selective on-line sample clean up and preconcentration of the nucleotides. The use of a miniaturized LC-ESMS system equipped with a column-switching technique will result in an amplified mass and concentration sensitivity.

Researcher(s)

• Promoter: Lemière Filip
• Co-promoter: Esmans Edgard
• Fellow: Tuytten Robin

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Lemière Filip

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Lemière Filip

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Esmans Edgard
• Co-promoter: Lemière Filip

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Lemière Filip

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Lemière Filip

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Lemière Filip
• Co-promoter: Esmans Edgard
• Fellow: Tuytten Robin

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Esmans Edgard
• Co-promoter: Lemière Filip
• Fellow: Geens Robin

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Lemière Filip

Research team(s)

Project type(s)

• Research Project