Jonathan GravesProf. Jonathan P. Graves is a Senior Scientist at EPFL and Honorary Visiting Professor at the University of York, UK. He achieved first class joint honours in Electronic Engineering and Mathematics from the University of Nottingham, UK in 1996. He completed his Ph.D. in Theoretical Mechanics from the University of Nottingham, UK, three years later in 1999. During his Ph.D. he was based in the Culham theory group of the United Kingdom Atomic Energy Authority, developing kinetic descriptions of the internal kink instability, and participating in deuterium-tritium experimental analysis in the Joint European Torus. After a short time in industry, and a postdoc at Nottingham University, he took a position at the Swiss Plasma Center at EPFL, becoming a Senior Scientist in 2014, and became an Honorary Visiting Professor at the University of York, UK, in 2020. In 2015 he became a member of the EUROfusion Scientific and Technical Advisory Committee (STAC) and a member of the EUROfusion DEMO Technical Advisory Group. He is on the editorial board for the journal Plasma Physics and Controlled Fusion, and in 2020 became Scientific Secretary of the Varenna-Lausanne International Workshop in Theory of Fusion Plasmas.
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.
Yann BarrandonYann Barrandon graduated in Medicine in Paris where he also trained as a dermatologist and completed his PhD on the long term cultivation of human haematopoietic stem cells in 1982 under the direction of Dr. Catherine Dresch (Centre Hayem, St Louis Hospital). He worked as a post-doctoral fellow (1982-1983) with Pr. Marvin Karasek in the Department of Dermatology at Stanford University CA, and then with Pr. Howard Green, a pioneer in cell therapy, in the Department of Molecular and Cellular Physiology at Harvard Medical School (1983-1990). During this period, he participated in the world's first transplantations of epidermal stem cells on extensive third degree wounds and contributed several seminal findings including the demonstration of stem cells in cultures of human keratinocytes (PNAS 1987), and that human keratinocyte stem cells could be efficiently transduced by retroviral vectors (Science 1987), in collaboration with Richard Mulligan at the Whitehead Institute for Biomedical Research (Massachussets Institute of Technology, Cambridge, USA). He has also participated to the transfer of the stem cell technology from Harvard University to a spin off biotechnology company, now part of Genzyme Corp.
He returned to France in 1990 as Director of Research at the INSERM and Head of Lab at the Ecole Normale Supérieure, Paris. During this period, he demonstrated the presence of multipotent clonogenic stem cells in hair follicles (Cell 1994, 2001) and successfully brought stem cells from bench to bedside demonstrating the usefulness of a fibrin matrix to transplant epidermal stem cells. (Transplantation, 2000). Following his move to Lausanne, Yann Barrandon has shown that oligopotent stem cells are present in the mammalian cornea (Nature 2008), challenging previous dogma. He has also contributed to the characterisation of several skin diseases (Nature Genetics, 1993a, 1993b, 2000, 2005) and towards gene therapy of dystrophic epidermolysis bullosa. He is a partner in several EEC stem cell consortia (FP6: Therapeuskin and EuroStemCell, FP7: EuroSyStem, OptiStem, BetaCellTherapy).
Current research targets the role of small microenvironmental variations on stem cell behavior, and exploring the potency of stem cells of stratified epithelia (skin, esophagus, ocular surface) and of thymic epithelial cells. The lab is also involved in understanding the factors that regulate stem cell engraftment to improve epithelial cell therapy. An important aspect of the research aims at setting up a pilot clinical trial to demonstrate the feasibility of ex vivo gene therapy to treat Dystrophic Epidermolysis Bullosa, a rare but horrendous congenital disease of the skin that results in continuous blistering of the skin, chronic wounds, fusion of fingers and development of carcinoma.
Yann Barrandon was a member of the Faculty Council of the EPFL School of Life Sciences 2006-2008, of the Board of Swiss Stem Cell Network, 2004-2009, and is a member of the EPFL Ethics Committee since 2008. He is a reviewer for major scientific journals and for major granting agencies abroad. He is a member of the board of Directors of the International Society for Differentiation (ISD) and of the Tissue Engineering and Regenerative Medicine International Society (TERMIS) and was a Member of the Board of Directors of the European Tissue Repair Society, 1990-1995. He was elected as EMBO member in 2009.
He has given over 300 invited conferences and seminars worldwide on the biology and the therapeutic use of cutaneous stem cells including:
Gordon Research Conferences, Tissue Repair and Regeneration, June 2005, New London, USA,
Keystone Symposia on Stem Cells, April 2006, Whistler, Canada
Keystone Symposia, Stem Cell Interactions with their Microenvironmental Niche, March 2007, Keystone, USA
Keystone Symposia, Stem Cell Niche Interactions, April 2009, Whistler, Canada
Gordon Research Conferences, Epithelial Stem Cells, June 2009, Les Diablerets, Switzerland
7th Meeting of the International Society Stem Cell Research, July 2009, Barcelona, Spain
16th International Society for Developmental Biologists, Edinburgh, Scotland, UK, Sept 2009
Yann Barrandon has given multiple media interviews and participated to different reportages:
LCI, TF1, France 2, France 3, RSR (Radio Suisse Romande), TSR (Television Suisse Romande), and articles in newspapers: Figaro, La Croix, Le Temps, LHebdo, Le Nouvelliste, etc. He was also a participant in the movie A Stem Cell Story, EuroStemCell, Best TV/video production, Tromsø Science Media Festival; Best short film, Scinema (Australia); In competition, Science Film Festival (Bangkok), BaKaFORUM 2007, Vedere la Scienza
He organized the second EuroStemCell international conference Advances in Stem Cell Research supported by the EMBO and held in Lausanne 8-10 September 2006. He regularly participates as faculty to the EEC funded Stem Cell Summer School held in Hydra Greece since 2005.
