Research programmes and collaborations

Teams based at the Biopark Charleroi Brussels South are part of the following programmes:



Interuniversity Attraction Poles, IAP

Interuniversity Attraction Poles (IAP) have received funding from the federal Belgian government for a period of 5 years. They take the form of networks for excellence in fundamental research, and foster relationships between the best Belgian teams and those abroad. For the period running from 2012-2017, Biopark laboratories will coordinate two IAPs, and are partners in a third.


"T lymphocytes: from basic biology to immunotherapy"

The project is coordinated by Oberdan Leo (IMI, ULB) and involves Muriel Moser's team (IBMM, ULb) and labs of VUB; UCLouvain; ULg; UGent; KULeuven; UHasselt; Australian National University (ANU) and Radboud University Nijmegen Medical Centre (RU).

The major objective of the present proposal is to gain insights into the mechanism whereby antigen-stimulated T lymphocytes acquire and express adequate effector function during an immune response. The long term goal of this project is to devise novel and efficient strategies for the immunotherapy of cancer. To be effective, the “cancer vaccines” need to address two major challenges: vaccination needs to stimulate the clonal expansion and differentiation of tumour-specific effector lymphocytes toward the desired phenotype (cytotoxic / inflammatory); suppressor mechanisms limiting immunotherapy need to be overcome. This long term goal requires therefore a better understanding of the molecular linguistics governing immune cells interactions.

The project reuniting nine different teams with expertise in fundamental and clinical immunology is structured around 5 themes: Differentiation and function of T helper subsets ; Mechanisms of immune suppression by regulatory T cells ; Understanding and reverting functional impairment of effector T cells ; Interplay between innate immunity and T cell responses ; Novel strategies for the induction of anti-tumour T cells.

The overall objective of this project is to devise strategies that would enable us to selectively induce, in clinical settings, the differentiation of antigen-specific T cells toward a pre-determined functional status (effector or regulator depending on the aimed pathology), while minimizing toxicity to healthy tissues.

More about this project in video (in French):



Tolerance and resistance to parasite infection: trypanosomatidae as paradigm

The project is coordinated by Benoit Vanhollebeke (IBMM, ULB) and involves teams of VUB, Institut de Médecine Tropical (Antwerp), Ludwig Maximilian University" (Munich, Germany) and Université d'Orléans (France).

Unravelling the mechanisms used by parasites to actively perturb the immune response and hereby intrude their host, and the mechanisms by which the host balances the inflammatory immune response required to eliminate these parasites while avoiding inflammation-associated tissue damage, represent a major challenge for public health programs. Researchers propose to use Trypanosomatidae as model organisms to investigate the dialogue between the parasite and its hosts.

Their main objectives are: to study how parasites counteract the capacity of the (insect and mammalian) host to eliminate the pathogen (called resistance to infection); to investigate how parasite - and vector - derived molecules modulate host (patho)physiology; to address how the host in turn attempts to control the tissue pathogenicity during parasite infection (called tolerance of the host to infection). This project is a direct continuation of the previous collaborative IAP network « Molecular dialogue between parasite and hosts: the trypanosome model ».

This project is the straight extension of the previous IAP "Molecular dialogue between parasite and hosts: the trypanosome model".



Role of developmental processes in the virulence oh human pathogens: from molecular mechanisms to novel therapeutic targets

The coordinator of this project is UGent. The network involves teams of UGent, ULB (Laurence Van Melderen, IBMM), KULeuven, FUNDP, UCL and UoM (US).


Many of the microbial processes important for the establishment of infections by bacteria or fungi can be considered « developmental processes ». For example, the transition from a planktonic cell to a biofilm cell attached to the host mucosal surface requires an intricate network of regulatory processes that determine the expression levels of a large number of genes. Similarly, the differentiation of microbial cells with normal physiology into antimicrobial-tolerant persister cells is another example of a developmental process involving strict regulation of metabolism and gene expression. Lastly, the successful colonization and development of infection in a human host requires the spatio-temporal regulation of the expression of virulence genes. The tight regulation of gene expression required to successfully complete these developmental processes is often directly influenced by complex interactions between microbial cells.

The overall aim of this project is to elucidate the regulatory mechanisms involved in key developmental processes in microorganisms. The objectives of this IAP projects are : to develop a number of unique state-of-the-art tools and implement and/or optimize them ; to gain a better understanding of the role of nutrient sensing in the development of single and multispecies biofilms in different conditions ; to obtain a detailed view of the mechanisms underlying the development of highly tolerant persister cells ; to elucidate the role of sRNA and proteins interacting with sRNA in microbial developmental processes ; to understand the role of intercellular communication in microbial developmental processes ; to study the differentiation of and infection by L-Proteobacteria.


Strategic Research Actions (SRA)

Funded by the Wallonia-Brussels Federation, Strategic Research Actions (SRA) are granted every two years by the Brussels Alliance for Research and Higher Education (ULB-UMONS), and consist of five-year projects that showcase the excellence of the teams that run them. The labs are home to two SRAs.


"The nucleolus in Health and Disease" (2014-2019)

The projet involves the RNA molecular biology Lab (Denis Lafontaine, IBMM) and the Nucleus Biology Lab (Birthe Fahrenkrog, IBMM)

Ribosomes and nuclear pore complexes (NPCs) are essential cellular nanomachines responsible for protein synthesis and nucleocytoplasmic trafficking, respectively. Ribosome synthesis is initiated in the nucleolus, a prominent, highly dynamic nuclear organelle central to gene expression. The morphology of the nucleolus is indicative of its function and cell health, and as such a potent disease biomarker and a target for cancer therapeutics.

Specific nucleoporins, the building blocks of NPCs, relocalize to the nucleolus upon inhibition of ribosomal RNA synthesis and in pathological situations, such as leukaemia. This project aims at understanding the principles of maintenance of nucleolar integrity and at investigating the emerging connections between disease-associated nucleoporins and the nucleolus.



"Genetic control of brain vascular development" (2014-2019)

The projet is lead by the Molecular Parasitology lab (Benoit Vanhollebeke, IBMM)

Despite the importance of the neurovascular unit in a large set of central nervous system disorders, the mechanisms underlying brain angiogenesis and brain endothelial specialization are unclear. GPR124, an orphan member of the adhesion class of heterotrimeric G protein-coupled receptors (aGPCR) is a key, yet poorly characterized regulator of brain-specific vascular assembly and differentiation.

Through the analysis of GPR124-deficient zebrafish, this project aims to understand the nature of the brain-derived molecular cues triggering GPR124 activation, the molecular and cellular impact of this activation on cerebral endothelial cell physiology as well as the potential molecular and genetic interactions between GPR124 signaling and other brain-specific proangiogenic signals.



"Patho-physiological role, structural analysis and drug targeting of ammonium/ammonia transport proteins of the conserved Mep-Amt-Rhesus factors family" (2012-2017)

The project is coordinated by Biology of membrane Transport laboratory (IBMM, Anna Maria Marini) and involves René Wintjens'team (Faculté de Pharmacie, ULB).

The ammonium ion is a ubiquitous molecule, used as principal source of nitrogen by microbes and plants. This ion is however a cytotoxic metabolite occupying a central position in the control of acid-base homeostasis in animals. IBMM (ULB) researchers played a pioneering role in the discovery of ammonium transport systems of the Mep-Amt-Rhesus family and in the elucidation of the physiological function of Rhesus factors in mammals.

By combining two laboratories of ULB with complementary skills, this project aims to characterize the new family Mep-Amt-Rhesus of transport proteins in a global approach and to evaluate their potential as drug targets in therapeutic scope. The lab's complementary skills together cover various scientific disciplines such as patho-physiology, molecular biology, biochemistry, protein sciences, bioinformatics and X-ray radiocrystallography.



"NAD metabolism and the control of innate immune responses" (2012-2017)

This project is coordinated by Laboratoire de Biologie moléculaire du Gène (Véronique Kruys, Cyril Gueydan, IBMM), in collaboration with Laboratoire d'Immunobiologie (Fabienne Andris, Muriel Moser, Guillaume Oldenhove, Oberdan Leo, IBMM).

In addition to its well-known role in energy metabolism, the nicotinamide adeline dinucleotide (NAD) has been recently shown to play an important role in the regulation of a vast array of cellular responses. The involvement of NAD in these regulatory processes is based on its ability to act as a substrate for a series of enzymes. Theses enzymes have been shown to regulate gene expression at both transcriptional and post-transcriptional steps, suggesting that intracellular NAD levels can have profound effects on cell physiology well beyond cellular energetics. Researchers have recently demonstrated that intracellular NAD levels can modulate the capacity of innate immune cells to produce pro-inflammatory mediators, suggesting a novel regulatory pathway linking cell metabolism to inflammation.

By combining in vitro and in vivo studies using invertebrate, mouse and human models, researchers wish to further explore the mechanisms by which intracellular NAD can modulate an innate immune response, possibly paving the way to the development of novel anti-inflammatory strategies of clinical relevance.

More about this project in video (in French):



Biowin, the Wallonia health and competitiveness cluster

A number of labs and companies based at Biopark Charleroi Brussels South are involved in the Biowin health and competitiveness cluster for Wallonia, where the health sector industry calls upon academic labs to lead research and development projects that are 100% relevant to the market.


DNAVac

Delphi Genetics, a ULB spin-off based in the Aéropole, coordinates the DNAVac project in partnership with ULg and UCL. The teams involved aim to develop and produce “DNA” vaccines that contain no genes that resist antibiotics.
Ongoing.


Radiotarget

Radiotarget unites teams from the CMMI (Biopark, ULB-UMONS) with those from the Université de Lièges, coordinated by IRE-Elit (National Radioelements Institute - Environmental and Lifescience Technologies). The aim of the programme is to develop antibodies coupled with a radioactive particle for use in the treatment of hepatic metastases.

More about this project in video (in French):


Learn more about all of these projects at http://www.biowin.org.


Queen Elisabeth Medical Foundation (QEMF)

The QEMF provides support to university teams that study the nervous system. In principle, selected programmes are awarded funding for three years.


The role of doublesex/mab3 related transcription (DMRT) in regionalisation of the cerebral cortex

2011-2013 team: Developmental Biology Lab (Eric Bellefroid, IBMM)

The cerebral cortex is one of the major regions of the brain responsible for the coordination of cognitive, motor, and sensory functions. It is a complex structure made up of hundreds of different types of neuron and glial cells, divided into six layers, where cells in different areas play different roles. The molecular mechanisms that control its development are still little understood, in particular those involved in defining the cortical regions.

The Developmental Biology lab has shown that the DMRT5 gene is expressed as a curve in the cerebral cortex’s progenitor cells: it is found in higher concentrations in the posterior-medial cerebral cortex, and plays a role in the regionalisation of cortical progenitors. The QEMF backed research project aims to better understand how the DMRT5 concentration is established in cortical progenitors, and how this transcription factor controls early regionalisation of the cerebral cortex.


Welbio: Institut wallon virtuel de recherche d'excellence dans les domaines des sciences de la vie (the Walloon virtual institute for excellence in life sciences)


Private-public partnerships (PPP)

Backed by the Region of Wallonia, the private-public partnerships (PPPs) involve a 2-year privileged partnership between university research teams and industrial partners with the aim of promoting the development and exploitation of scientific innovations. Four PPPs are currently underway in the Biopark:

EMULVAC & SAPOVAC

Team involved (2013-2015): Groupe de recherche de Stanislas Goriely (IMI), en collaboration avec GSK-Biologicals

These two projects are focused on studying and understanding how vaccine adjuvants function. While EMULVAC concentrates on the emulsion-based adjuvants used in seasonal influenza vaccines, SAPOVAC is focused on saponins, used especially in the candidate vaccine against malaria. Though these two types of adjuvants are already being used by GSK-Biologicals, the company sponsoring the two programmes, the way they actually work remains unclear. The researchers will therefore be trying to understand which molecular pathways are activated by these adjuvants, thus having a stimulating effect on the innate immunity of cells. Gaining such an understanding could for example help us improve current vaccination strategies in terms of effectiveness and reactogenicity.

TREGCD70

Team involved (2013-2015): Laboratoire d'Immunobiologie (Muriel Moser, IBMM), en collaboration avec GSK-Biologicals

The TREGCD70 project is the continuation of CIBLES, the excellence programme completed in December 2012. In the course of this programme, researchers discovered that certain regulatory T lymphocytes were able to control the inflammatory immune response by decreasing the expression of the CD70 molecule on the surface of dendritic cells, the sentinels of our immune system. This reduction goes hand in hand with a transfer of the corresponding CD27 receptor to the surface to the same cells. The aim of this PPP, sponsored by GSK-Biologicals, the company which already sponsored the CIBLES programme, will be to understand this process and to find ways of leveraging it to control immune responses, in particular in the field of autoimmune diabetes.

OSCIRC

Team involved (2013-2015): Department of Rheumatology and Physical Medicine (Valérie Gangji, Erasmus Hospital), in collaboration with Bone Therapeutics

The project focuses on circulating osteoblasts, bone precursors found in the blood. When a bone is fractured, they have the ability to recognise the fracture, find their way to it and help set the bone. The aim of this PPP is to understand what makes these osteoblasts enter the blood and what guides them to the fracture. The baseline objective here is to try and develop cell therapies which can be administered intravenously to remedy such bone diseases as osteoporosis, osteonecrosis or pseudarthrosis - an interesting project with market potential for Bone Therapeutics, a company already involved in the development of cell therapy products for treating such diseases.


CIBLES Excellence Programme

The economic and social restructuring plan for Wallonia – the “Marshall Plan” for Wallonia – saw the launch of programmes for excellence that would serve to boost research and innovation in synch with business. The programmes for excellence must meet objective criteria that not only verify the project’s scientific foundations (interuniversity project involving internationally renowned research teams), but also to guarantee that the projects reach scientific and economic fruition, especially through partnerships with the private sector, patent applications, and the creation of spin-offs.

The second programme for excellence is known as CIBLES. Funded for five-years with a budget of €25m, the programme is coordinated by teams captained by the professors Etienne Pays (IBMM, ULB) and Marc Parmentier (Interdisciplinary Research in Human and Molecular Biology Laboratory - IRIBHM, ULB), and involves teams from UCL and ULg.

Its aim? To identify and validate innovative treatment strategies and targets, concentrating on pathologies related to chronic inflammation and the nervous system, with a view to developing new generations of drugs. The project benefits from a partnership with industry, enjoying the support of UCB, GSK, and the Biopark spin-off, Euroscreen. The CIBLES project is managed by the ULB professors Etienne Pays (IBMM) and Marc Parmentier (IRIBHM), and involves teams from the UCL and ULg.

CIBLES is focussed on three themes: research into receptors coupled with G proteins, research into selecting especially promising targets pertinent to inflammation, apoliprotein L and the IDO enzyme, and, finally, the applications of stem cells in the treatment of central nervous system diseases, as well as in cancer.


The European funds - ERDF and ESF


The Biopark participated in the European "Immunomarqueurs" (immunological markers) project and in two university-business collaboration projects, all co-financed by the European Regional Development Fund (ERDF). One should similarly not forget the role played by these funds in the setting up and functioning of IBMM and IMI. Biopark Formation is a further programme benefiting from European support, this time from the European Social Fund (ESF).

CWALity program


OSTEOMOD

Bone Therapeutics and CMMI

Funded by Wallonia, the CWALity OSTEOMOD project is the fruit of a partnership between Bone Therapeutics and the CMMI, and uses a combination of imaging techniques to provide a non-invasive alternative to histology. It can obtain reliable results with no need to sacrifice animals and provides truly dynamic in situ monitoring of repairs to bone defects.



Beware Academia


NEURON

Delphi Genetics et Laboratoire de Génétique du développement (Eric Bellefroid)

The “Neuron” BEWARE project led by Eric Bellefroid at the Developmental Genetics Laboratory sets out to examine neural differentiation and diversification mechanisms. The project’s aim is to obtain high quality antibodies that can be used in chromatin immunopreciptation against the Myt1L, Myt1 and NZF3 transcription factors that enable non-neural cells to trans-differentiate into neurons. The research should improve our understanding of how they work, and the origins of human diseases in which these genes play a role



First International


CORTEX

Laboratoire de Génétique du développement (Eric Bellefroid), Delphi Genetics, Erasmus Medical Center (Rotterdam), National Institute for Medical Research (London)

Funded by Wallonia for 3 years, this project focuses on Dmrt transcription factors in the development of the cerebral cortex. By working with Delphi Genetics, researchers hope to obtain high quality antibodies for Dmrt3-5 factors, as well as to validate their immunisation technique.



Previous projects

  • IAP project "Structural, biochemical and physiological analysis of amino acid transporters and sensors" - Physiologie Moléculaire de la Cellule (Bruno André) - Ended in 2015

  • WELBIO project "ApoL1 protein in renal physiology" - Molecular Parasitology Lab (Etienne Pays) - Ended in 2013

  • BioWin project "Keymarker" - IBMMand DNA Vision - Ended in 2014

  • BioWin project "Hope 4 PD" - Euroscreen - Ended in 2013

  • BioWin project "Join T-AIC" - Bone Therapeutics - Ended in 2013

  • BioWin project "Cantol" - Euroscreen and IBMM labs - Ended in 2012