Henry MarkramHenry Markram started a dual scientific and medical career at the University of Cape Town, in South Africa. His scientific work in the 80s revealed the polymodal receptive fields of pontomedullary reticular formation neurons in vivo and how acetylcholine re-organized these sensory maps.
He moved to Israel in 1988 and obtained his PhD at the Weizmann Institute where he discovered a link between acetylcholine and memory mechanisms by being the first to show that acetylcholine modulates the NMDA receptor in vitro studies, and thereby gates which synapses can undergo synaptic plasticity. He was also the first to characterize the electrical and anatomical properties of the cholinergic neurons in the medial septum diagonal band.
He carried out a first postdoctoral study as a Fulbright Scholar at the NIH, on the biophysics of ion channels on synaptic vesicles using sub-fractionation methods to isolate synaptic vesicles and patch-clamp recordings to characterize the ion channels. He carried out a second postdoctoral study at the Max Planck Institute, as a Minerva Fellow, where he discovered that individual action potentials propagating back into dendrites also cause pulsed influx of Ca2 into the dendrites and found that sub-threshold activity could also activated a low threshold Ca2 channel. He developed a model to show how different types of electrical activities can divert Ca2 to activate different intracellular targets depending on the speed of Ca2 influx an insight that helps explain how Ca2 acts as a universal second messenger. His most well known discovery is that of the millisecond watershed to judge the relevance of communication between neurons marked by the back-propagating action potential. This phenomenon is now called Spike Timing Dependent Plasticity (STDP), which many laboratories around the world have subsequently found in multiple brain regions and many theoreticians have incorporated as a learning rule. At the Max-Planck he also started exploring the micro-anatomical and physiological principles of the different neurons of the neocortex and of the mono-synaptic connections that they form - the first step towards a systematic reverse engineering of the neocortical microcircuitry to derive the blue prints of the cortical column in a manner that would allow computer model reconstruction.
He received a tenure track position at the Weizmann Institute where he continued the reverse engineering studies and also discovered a number of core principles of the structural and functional organization such as differential signaling onto different neurons, models of dynamic synapses with Misha Tsodyks, the computational functions of dynamic synapses, and how GABAergic neurons map onto interneurons and pyramidal neurons. A major contribution during this period was his discovery of Redistribution of Synaptic Efficacy (RSE), where he showed that co-activation of neurons does not only alter synaptic strength, but also the dynamics of transmission. At the Weizmann, he also found the tabula rasa principle which governs the random structural connectivity between pyramidal neurons and a non-random functional connectivity due to target selection. Markram also developed a novel computation framework with Wolfgang Maass to account for the impact of multiple time constants in neurons and synapses on information processing called liquid computing or high entropy computing.
In 2002, he was appointed Full professor at the EPFL where he founded and directed the Brain Mind Institute. During this time Markram continued his reverse engineering approaches and developed a series of new technologies to allow large-scale multi-neuron patch-clamp studies. Markrams lab discovered a novel microcircuit plasticity phenomenon where connections are formed and eliminated in a Darwinian manner as apposed to where synapses are strengthening or weakened as found for LTP. This was the first demonstration that neural circuits are constantly being re-wired and excitation can boost the rate of re-wiring.
At the EPFL he also completed the much of the reverse engineering studies on the neocortical microcircuitry, revealing deeper insight into the circuit design and built databases of the blue-print of the cortical column. In 2005 he used these databases to launched the Blue Brain Project. The BBP used IBMs most advanced supercomputers to reconstruct a detailed computer model of the neocortical column composed of 10000 neurons, more than 340 different types of neurons distributed according to a layer-based recipe of composition and interconnected with 30 million synapses (6 different types) according to synaptic mapping recipes. The Blue Brain team built dozens of applications that now allow automated reconstruction, simulation, visualization, analysis and calibration of detailed microcircuits. This Proof of Concept completed, Markrams lab has now set the agenda towards whole brain and molecular modeling.
With an in depth understanding of the neocortical microcircuit, Markram set a path to determine how the neocortex changes in Autism. He found hyper-reactivity due to hyper-connectivity in the circuitry and hyper-plasticity due to hyper-NMDA expression. Similar findings in the Amygdala together with behavioral evidence that the animal model of autism expressed hyper-fear led to the novel theory of Autism called the Intense World Syndrome proposed by Henry and Kamila Markram. The Intense World Syndrome claims that the brain of an Autist is hyper-sensitive and hyper-plastic which renders the world painfully intense and the brain overly autonomous. The theory is acquiring rapid recognition and many new studies have extended the findings to other brain regions and to other models of autism.
Markram aims to eventually build detailed computer models of brains of mammals to pioneer simulation-based research in the neuroscience which could serve to aggregate, integrate, unify and validate our knowledge of the brain and to use such a facility as a new tool to explore the emergence of intelligence and higher cognitive functions in the brain, and explore hypotheses of diseases as well as treatments.
Kristina SchoonjansExpertise
Bile acid signalingNutrient sensingIntermediary metabolismMetabolic disorders
Teaching & PhD PhD Students Adrien Faure Past EPFL PhD Students Pan Xu, Ece Yildiz, Nadia Bresciani, Yu Sun, Francesca Pontanari, Alejandro Alonso Calleja Past EPFL PhD Students as codirector Mitsunori Nomura, Pan Xu, Katyayanee Neopane, Lucie Camille Chanvillard, Jakob Josef Langer, Bilge Sen Elçi Courses General Biology BIOENG-110 The purpose of the course is to provide a general overview of the biolo
Didier TronoAfter obtaining an M.D. from the University of Geneva and completing a clinical training in pathology, internal medicine and infectious diseases in Geneva and at Massachusetts General Hospital in Boston, Didier Trono embarked in a scientific career at the Whitehead Institute for Biomedical Research of MIT. In 1990, he joined the faculty of the Salk Institute for Biological Studies to launch a center for AIDS research. He moved back to Europe seven years later, before taking the reins of the newly created EPFL School of Life Sciences, which he directed from 2004 to 2012. He is now actively engaged in the efforts of Switzerland to integrate new technologies in the fields of precision medicine and personalized health.
Johan AuwerxJohan Auwerx is Professor at the École Polytechnique Fédérale in Lausanne, Switzerland, where he occupies the Nestle Chair in Energy Metabolism. Dr. Auwerx has been using molecular physiology and systems genetics to understand metabolism in health, aging and disease. Much of his work focused on understanding how diet, exercise and hormones control metabolism through changing the expression of genes by altering the activity of transcription factors and their associated cofactors. His work was instrumental for the development of agonists of nuclear receptors - a particular class of transcription factors - into drugs, which now are used to treat high blood lipid levels, fatty liver, and type 2 diabetes. Dr. Auwerx was amongst the first to recognize that transcriptional cofactors, which fine-tune the activity of transcription factors, act as energy sensors/effectors that influence metabolic homeostasis. His research validated these cofactors as novel targets to treat metabolic diseases, and spurred the clinical use of natural compounds, such as resveratrol, as modulators of these cofactor pathways.
Johan Auwerx was elected as a member of EMBO in 2003 and is the recipient of a dozen of international scientific prizes, including the Danone International Nutrition Award, the Oskar Minkowski Prize, and the Morgagni Gold Medal. His work is highly cited by his peers with a h-factor of over 100. He is an editorial board member of several journals, including Cell Metabolism, Molecular Systems Biology, The EMBO Journal, Journal of Cell Biology, Cell, and Science. Dr. Auwerx co-founded a handful of biotech companies, including Carex, PhytoDia, and most recently Mitobridge, and has served on several scientific advisory boards.
Dr. Auwerx received both his MD and PhD in Molecular Endocrinology at the Katholieke Universiteit in Leuven, Belgium. He was a post-doctoral research fellow in the Departments of Medicine and Genetics of the University of Washington in Seattle.
Stewart ColeProfessor Stewart Cole is an international authority in bacterial molecular-genetics and genomics. He has made outstanding contributions in several fields including: bacterial anaerobic electron transport; genome analysis of retroviruses and papillomaviruses; antibiotic resistance mechanisms; and the molecular microbiology of toxigenic clostridia. His studies on isoniazid and multidrug resistance in Mycobacterium tuberculosis, together with his pioneering work on the pathogenicity, evolution and genomics of the tubercle and leprosy bacilli, have made him an undisputed leader in the field of mycobacterial research. The findings of his research are of direct relevance to public health and disease-control in both the developing world and the industrialised nations. He has published over 250 scientific papers and review articles, and holds many patents.
Vassily HatzimanikatisDr. Vassily Hatzimanikatis is currently Associate Professor of Chemical Engineering and Bioengineering at Ecole Polytechnique Federale de Lausanne (EPFL), in Lausanne, Switzerland. Vassily received a PhD and an MS in Chemical Engineering from the California Institute of Technology, and his Diploma in Chemical Engineering from the University of Patras, in Greece. After the completion of his doctoral studies, he held a research group leader position at the Swiss Federal Institute of Technology in Zurich (ETHZ), Switzerland. Prior to joining EPFL, Vassily worked for three years in DuPont, Cargill, and Cargill Dow, and he has been assistant professor at Northwestern University, at Illinois, USA.
Vassilys research interests are in the areas of computational systems biology, biotechnology, and complexity. He is associate editor of the journals Biotechnology & Bioengineering, Metabolic Engineering and Integrative Biology, and he serves on the editorial advisory board of the journals Bioprocess and Biosystems Engineering, Journal of Chemical Technology and Biotechnology, and Industrial Biotechnology. He has written over 70 technical publications and he is co-inventor in three patents and patent applications.
Vassily is a fellow of the American Institute for Medical and Biological Engineering (2010), he was a DuPont Young Professor (2001-2004), and he has also received the Jay Bailey Young Investigator Award in Metabolic Engineering (2000), and the ACS Elmar Gaden Award (2011).
Harm-Anton KlokExpertise
Polymer design at nanoscaleBiologically-inspired polymers
Mission
Research at the Laboratory of Polymer (LP) focuses on the development of novel advanced polymeric materials with potential applications in optics, electronics or medicine. The philosophy is that precise control over nanoscale structure is an important prerequisite to tailor polymer properties. To this end, a “bottom-up” approach is followed, which starts with designing a new material at the molecular level, in order to be able to pr
Rolf GruetterAwards:
1999 Young Investigator Award Plenary Lectureship
, International Society for Neurochemistry
2011 Fellow
, ESMRMB
2011 Teaching Award
, Section Sciences de la Vie, EPFL
Harald Hirlingsince 2018:Adjoint du Doyen SV, Responsable Finance SVsince 2008: Adjoint du Doyen SV 2002-2010: Adjoint scientifique, SV-LNC, EPFL 2006-2008: Adjoint de Section SSV 2003-2004: coordinator (directeur) of the doctoral program in Neuroscience, EPFL Doctoral School 1994-2001: University of Lausanne Stanford University Institut Curie, Paris Education: ISREC, Epalinges (Switzerland). University of Konstanz (Germany)
Graham KnottGraham Knott received his degree in physiology from the University of Southampton, UK, in 1990, and his PhD in neuroscience from the University of Tasmania, Australia, in 1995. He moved to the University of Lausanne in Switzerland in 1999 where he researched the plasticity of neuronal connectivity in the adult brain, developing correlative light and electron microscopy methods for the analysis of in vivo imaged neurons. In 2006 Graham joined the Ecole Polytechnique Fédérale de Lausanne, establishing the Bio Electron Microscopy Facility and has continued his research interests in brain plasticity and 3D electron microscopy.
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