ULB Neuroscience Institute

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The ULB Neuroscience Institute has been launched on May 2013 thanks to the financial support of notably the Fondation ULB.

Pr. MD. Pierre Vanderhaeghen is the Head of the ULB Neuroscience Institute, to know more about him and his laboratory

The cerebral cortex is one of the most complex and important structures in our brain. In correlation with its elaborate functions, it is characterized by a huge diversity of neuronal identities, each cortical neuron displaying specific patterns of gene expression and synaptic connectivity. The mechanisms of formation of cortical networks have direct relevance to several diseases, such as epilepsy, autism, and mental disorders, as well as for the development of rationally designed cell therapies for neurological conditions such as Alzheimer’s disease or stroke.

The ULB Neuroscience Institute

1. Overview of the Ulb Neuroscience Institute (UNI).

The Université Libre de Bruxelles (ULB) has a long standing tradition of excellence in biomedical research. With increasing competition at both European and non-European levels, it has become clear that ULB has to move forward in diversifying its means to maintain and develop excellence further, based on a approach that puts emphasis on (1) focus, and (2) critical mass. In this frame ULB has identified a few disciplines that were chosen because they already constitute an attractive critical mass of excellence, and Neuroscience is one of them. Neuroscience was thought to be particularly attractive also because of its intrinsic interdisciplinary nature, thus bridging together researchers from very different horizons, from molecular neurobiologists to cognitive scientists and neuroclinicians.

ULB aims at affirming neuroscience research as one of its primary poles, through the creation of a unifying structure, a ULB Neuroscience Institute (UNI), which enables to bring together and build up synergies between all ULB brain / cognition scientists from the Medical School, the Engineering School, the Faculty of Science, the Faculty of Psychological Sciences, and the Faculty of Mobility Sciences.

The ULB Institute of Neuroscience aims at:

• generating a critical mass of human resources and advanced technology through dynamic recruitment strategies;

• establishing new synergies between neuroresearchers from different backgrounds;

The UNI supports specific interdisciplinary programs or research focusing on brain development, degeneration, and repair. In this frame it will also aim at the recruitment of young promising Group Leaders, recruited from abroad (outside of ULB), who will build their own new laboratory, thus expanding in a coordinated fashion the skills and scientific strength of ULB Neuroscience Community. These new laboratories will undertake specific research activities along new lines of exploration of brain circuits formation and function, and will create new synergies with existing teams.

The assets of ULB: at the forefront in diverse areas of brain research.

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For many years, ULB has been at the forefront of brain research, from clinical neurosciences to molecular and cellular neurobiology, to cognitive sciences and neuropsychology. It currently groups about 20 different laboratories, located mostly in the Medical School and the Faculty of Psychological Sciences, but also in the Engineering School and in the Faculties of Science and of Mobility Sciences.

The research topics of ULB laboratories cover a wide range of today’s neurosciences, including neuropharmacology, neurobiology of addition, neurogenetics of epilepsy, mechanisms of neurodegeneration, brain development and its diseases, physiology of motor systems, physiology of learning and sleep, neural bases of consciousness, neural stem cells and brain repair, sensory-motor integration, neural basis of language acquisition, as well as fundamental research in cognitive sciences and artificial intelligence. Overall, ULB neuroscience laboatories published more than 2500 publications in peer-reviewed international journals (including Nature, Science, Cell, Nature Neuroscience, Neuron, Journal of Neuroscience, Brain,…) leading to more than 85000 citations for the last ten years (Scopus).

In addition, ULB has implemented and/or developed an array of brain exploration technologies that is unique in Belgium. It includes a state of the art facility for the exploration of the living human brain (Magnetic Resonance Imaging, PET scan, Magnetoencephalography) and high resolution imaging tools for experimental models (confocal microscopy, multiphoton microscopy, time-lapse imaging, micro-PET). ULB also developed specific technologies devoted to molecular/cellular studies including genomics / bioinformatics, transgenics, pluripotent stem cell reprogramming and brain transplantation.

The brain: a major challenge for science, medicine, and society.

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The brain is the most complex organ in our body. To a large extent it is what makes us what we are as human beings, as individuals, and as a species.

Understanding how the brain develops and works remains a major basic scientific question today. Besides, it is of primal importance to develop novel therapeutic strategies for brain diseases, many of which remain without efficient treatments as of today.

Indeed, brain diseases are evaluated to affect more than 100 million people in Europe and constitute a major challenge for the whole society. Beyond the handicap and suffering of the affected individuals and their family, the total financial burden associated with brain diseases (most common including Alzheimer and Parkinson’s, addiction, depression, epilepsy, migraine, mental and motor retardation and handicaps) is estimated to 400 billions euros/year in Europe, and 35% of all medical costs are estimated to be spent in the frame of brain diseases (Belgian Brain Council; Acta Neurol Belg. 2006 Dec;106(4):208-14.).

Brain function relies on multiple levels of complexity interacting with each other: from genes to neurons, from neurons to neural circuits, from neural circuits to perception, behaviour, and consciousness. These interactions constitute the neural basis of brain function, but they remain very challenging to integrate. For these reasons, despite advances in neuroscience over the last twenty years, our understanding of the brain and its diseases are lagging behind those of other biomedical topics, such as immunology and molecular biology for instance.

Indeed, to understand how the brain works or dysfunctions, we must discover the mechanisms by which various levels of complexity of the nervous system are interconnected, and reveal the precise chain that links the microscopic level of molecules and cells to the higher levels of mind and consciousness. This is what requires a multidisciplinary approach, taking into account all dimensions of brain complexity.

Tackling the multiple levels of brain complexity through multidisciplinary approaches.

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Facing these challenges, ULB has chosen to develop an innovative approach: to combine and synergize the best ULB neuroscience teams within an Institute for Neuroscience, comprising scientists from very different backgrounds, from genetics to psychology, from neurobiology to clinical disciplines, and even to artificial intelligence.  The central concept is to bring together researchers, techniques and concepts, in order to tackle complex and important issues from multiple angles, so that researchers in each neurodiscipline can “see” the same problem from a new perspective, thereby enabling new discoveries. Of course, given the diversity of the concepts and techniques involved, the Institute does not envision a completely integrated research where all scientists would work within a single network on a single project, but rather to create a few specific “niches” where subgroups of neuroscientists with distinct, but related interests approaches will cross-fertilize each other by combining various techniques and concepts tailored to different levels of brain complexity.

Two main research areas: brain development and neurodegeneration/brain repair.

Taking into account both the current existing strengths at ULB, and the emerging themes in today’s neurosciences, two major research areas will be emphasized specifically in the frame of the Chair: (1) the mechanisms of brain development, in particular of higher cognitive functions, and (2) new approaches to neurodegeneration, including brain repair.

Brain development and acquisition of higher cognitive functions.

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The cerebral cortex is the most complex structure in the human brain and the major site of higher cognitive functions specific to our species. A variety of brain diseases result from altered development the cortex, from mental retardation to autistic syndromes or epilepsy.

While several mechanisms underlying cortical development have been identified through the use of model animals, many remain to be uncovered, in particular given species-specific nature of the cortex, which has undergone considerable evolution in primates and humans.

On the other hand, neurogenetic disorders are particularly interesting since they enable in principle to identify in an unbiased way which genes are indeed required for the full acquisition of normal cognitive functions.

The combination of neurogenetics, together with the development of human cellular models of brain diseases using pluripotent stem cell technology, represent a potentially powerful way towards the discovery of novel mechanisms underlying human-specific brain function.

In a multidisciplinary perspective, ULB teams involved in neurogenetics will seek genetic alterations that are associated with impaired learning and cognitive development, including autistic syndromes and epilepsy, using exome sequencing centred on a carefully selected cohort of patients recruited through the wide ULB clinical network. This will enable to identify candidate causal or predisposing factors to cognitive impairment, thus generating new tools for early detection and prevention of these diseases, while providing the essential components for an in-depth understanding of the underlying mechanisms.

In conjunction with this research focused on neurogenetics, the mechanisms underlying normal and abnormal cognitive development will be dissected through the use of new technologies involving pluripotent stem cells (of embryonic origin (ESC) or induced (iPSC), which constitutes a unique opportunity to study experimentally human brain development and disease. These stem cells can now be generated from skin cells of patients with neurogenetic diseases, and then be transformed into neurons that have all the native properties of the neurons from the patient’s brain, including the cerebral cortex (this process of “intrinsic corticogenesis” is one of the primary discoveries of Pr. Vanderhaeghen – which justified awarding him the prestigious Francqui Prize – Gaspard et al. Nature 2008). This revolutionary tool allows the generation of “models” of nervous diseases, focused on the patients’ cells.

In addition, the same genes will be studied in transgenic animal models (i.e. mouse), integrating behavioural studies and analyses of neuronal activity. The different models, in human cells and in vivo in the mouse, will enable determining specific links between selective genetic pathways and development of the neural circuits underlying higher brain functions.

Research on neurodegenerative diseases: developing human cellular models of brain diseases and testing brain repair using pluripotent stem cell technology

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Most neurodegenerative diseases remain without a cure, but most importantly at this stage, they also remain without enough insight on the exact causal mechanisms involved. One of the main issues in research on the mechanisms of neural aging and neurodegeneration is that they are poorly recapitulated by animal models: for instance some of the primary neuronal lesions present in the brain of human patients with Alzheimer’s disease, cannot be modelled properly in mouse transgenic models.

In this context, the models of in vitro neuronal generation from human pluripotent stem cells may offer entirely new prospects to create human models relevant to study basic disease mechanisms. Following model development, the research will be taken steps further by ULB teams specifically interested in physiopathology of neurodegenerative mechanisms.

On the other hand, stem cell technology will also be used to test and develop innovative approaches towards brain repair, by grafting cortical-like neural cells generated in vitro from pluripotent stem cells, into animal models of brain lesions. Analyses in neurophysiology, behaviour and functional neuroimaging will then determine the relationship between cellular / molecular levels and higher levels of brain function, in order to accurately assess the relevance of newly proposed approaches to the patient’s benefit.

In addition, the functional impact of brain repair will be studied further with new multidisciplinary technologies, which essentially aim to study “global” brain function and circuitry, but at the reductionist, microscopic level of neuronal cells and genes.

To discover the many ULB laboratories involved in the ULB Neuroscience Institute

http://uni.ulb.ac.be/groups-2/


La fiche du projet disponible en PDF ici.

Selected publications:

Pyramidal neurons derived from human pluripotent stem cells integrate efficiently into mouse brain circuits in vivoEspuny-Camacho I, Michelsen K, Gall D, Linaro D, Hasche A, Bonnefont J, Bali C, Orduz D, Bilheu A, Herpoel A, Lambert N, Gaspard N, Peron S, Schiffmann S, Giugliano M, Gaillard A, Vanderhaeghen PNEURON, 77, 440-56, 2013
Ephrin-B1 controls the columnar distribution of cortical pyramidal neurons by restricting their tangential migrationDimidschstein J, Passante L, Dufour A, Van Den Ameele J, Tiberi L, Hrechdakian T, Adams r, Klein R, Lie D, Jossin Y, Vanderhaeghen PNEURON, 79, 1123-35, 2013
BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targetsTiberi L, Van Den Ameele J, Dimidschstein J, Piccirilli J, Gall D, Herpoel A, Bilheu A, Bonnefont J, Iacovino M, Kyba M, Bouschet T, Vanderhaeghen PNATURE NEUROSCIENCE, 15, 1627-35, 2012
An intrinsic mechanism of corticogenesis from embryonic stem cellsGaspard N, Bouschet T, Hourez R, Dimidschstein J, Naeije G, Van Den Ameele J, Espuny-Camacho I, Herpoel A, Passante L, Schiffmann S, Gaillard A, Vanderhaeghen PNATURE, 455, 351-7, 2008
Ephrin signalling controls brain size by regulating apoptosis of neural progenitorsDepaepe V, Suarez-Gonzalez N, Dufour A, Passante L, Gorski J, Jones K, Ledent C, Vanderhaeghen PNATURE, 435, 1244-50, 2005