Daniel ConstamDaniel Constam received his doctoral degree in Natural Sciences from ETH Zürich in the neuroimmunology group of Adriano Fontana (1993). For postdoctoral studies, he joined the laboratory of Elizabeth Robertson as an EMBO fellow at Harvard University to characterize proprotein convertase (PC) functions in mouse models of early embryogenesis (1994-1999). As an ISREC group leader (>2000) and Associate Professor at EPFL (>2007), he initially continued to study pluripotency and lineage differentiation during development and found that several secreted PCs jointly regulate cell-cell adhesion and TGFβ signaling pathways at the cross-roads of stem cell and cancer biology. To map the proteolytic activity of PCs and their relative distribution in exocytic or endocytic vesicles, his lab developed PC-specific FRET sensors for high resolution live imaging in normal cells and in tumour-host interactions. His studies on TGFβ signaling also identified the RNA-binding protein Bicc1 and its self-polymerization in membrane-less organelles as regulators of mRNA translation and cell metabolism that cooperate with primary cilia to prevent cystic growth in renal tubules and in pancreatic and bile ducts.
Cathrin BriskenCathrin Brisken, MD, PhD, is Associate Professor of Life Sciences at the Swiss Federal Institute of Technology Lausanne (EPFL). Dr. Brisken is internationally recognized for her work on endocrine control of mammary gland development and breast carcinogenesis.
Dr. Brisken received her MD and her PhD degree in Biophysics from the Georg August University of Göttingen, Germany. She completed her postdoctoral work in cancer biology with Dr. R.A. Weinberg at the Whitehead Institute of Biomedical Research in Cambridge, MA, USA. She previously held appointments at the Cancer Center of the Massachusetts General Hospital, Harvard Medical School, Boston and the Swiss Institute for Experimental Cancer Research (ISREC).
Research in Dr. Brisken’s laboratory focuses on the cellular and molecular underpinnings of estrogen and progesterone receptor signaling in the breast and the respective roles of these hormones and hormonally active compounds in carcinogenesis. The aim is to understand how recurrent exposures to endogenous and exogenous hormones contribute to breast carcinogenesis in order to better prevent and treat the disease. The laboratory has pioneered in vivo approaches to genetically dissect the role of the reproductive hormones in driving mouse mammary gland development and shown how they control intercellular communication. Dr. Brisken’s group has developed ex vivo and humanized mouse models using patient samples to study hormone action in human tissues in normal settings and during disease progression.
Dr. Brisken is member of the International Breast Cancer Study Group (IBCSG) Biological Protocol Working Group. She served as Dean of EPFL Doctoral School (more than 2000 PhD students in 18 PhD programs), as member of the Hinterzartener Kreis, the oncology think-tank associated with the German Science Foundation, and numerous Swiss, European, and AACR committees. She co-founded the International Cancer Prevention Institute.
Maria del Carmen Sandi PerezACADEMIC POSITION:
Professor, Director of the Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland.
EDUCATION:
BS MS Salamanca, Spain, 1984
PhD Cajal Institute, CSIC, and University Autonoma of Madrid, Spain, 1988
PROFESSIONAL EXPERIENCE:
Postdoc at INSERM, Bordeaux, France, and Cajal Institute Madrid, Spain, 1989-1990
Postdoc at the Open University, UK, 1991-1992, 1996
Research Associate, Cajal Institute, CSIC, Madrid, 1993-1995
Associate Professor Tenured, UNED University, Madrid, 1996-2003
Sabbatical Professor, University of Bern, Switzerland, 2002-2003
Assistant Professor Tenure-Track, EPFL, 2003-2007
Associate Professor Tenured, EPFL, 2007-2012
Full Professor, EPFL, 2012-
Director, Brain Mind Institute, EPFL, 2012-
PRINCIPAL BOARDS:
President, European Brain and Behavior Society (EBBS), 2009-2012
Editor-in-Chief Frontiers in Behavioral Neuroscience
Member of Scientific Advisory Panel, European College Neuropsychopharmacology (ECNP)
Member of the European Dana Alliance for the Brain (EDAB)
Associate Editor Frontiers in Neuroscience
Editorial Board Member Neurobiology of Learning and Memory
Editorial Board Member Journal of Psychiatry Research
Editorial Board Member Stress
Editorial Board Member Biology of Mood and Anxiety Disorders
Editorial Board Member Neuroscience and Biobehavioral Reviews
John McKinneyProfessor John McKinney received his Ph.D. from The Rockefeller University (New York, NY) in 1994 for studies on cell cycle regulation in
Saccharomyces cerevisiae
in the laboratory of Fred Cross. From 1995 to 1998, he was a postdoctoral fellow in the laboratory of William Jacobs at the Albert Einstein College of Medicine (Bronx, NY), where he studied mechanisms of persistence in
Mycobacterium tuberculosis
. In 1999, he returned to Rockefeller University to establish his own laboratory as an Assistant (1999-2004) and then Associate (2004-2007) Professor. In July 2007, the lab relocated to the Global Health Institute in the School of Life Sciences at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, where McKinney is Professor and Head of the Laboratory of Microbiology and Microsystems (LMIC). Our research focuses on understanding the mechanistic basis of bacterial persistence in the context of host immunity and antimicrobial therapy, using
M. tuberculosis
as a "model" system.
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.
Jacques FellayJacques Fellay is a medical scientist with expertise in infectious diseases and human genomics. He obtained his MD from the University of Lausanne in 2002 and his PhD from University of Utrecht. After a clinical training in infectious diseases in Switzerland and a 4-years postdoctoral fellowship at Duke University, he joined the EPFL in April 2011 with an SNF Professorship.
On top of his EPFL affiliation, Jacques is also Head of Precision Medicine at the University Hospital (CHUV) in Lausanne, Group Leader at the Swiss Institute of Bioinformatics, and Co-director of the Health2030 Genome Center at Campus Biotech in Geneva.
