Concept
Molecular genetics
Related people (23)
Stewart Cole
Professor 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.
Johan Auwerx
Johan 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.
Jacques Fellay
Jacques 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.
Denis Duboule
Denis Duboule is born in 1955 and is both swiss and french national. He studied biology at the university of Geneva, where he obtained a PhD in mammalian embryology in 1984. He then spent 10 years abroad, first as a group leader in the medical faculty in Strasbourg (France), then at the European Laboratory for Molecular Biology (EMBL) in Germany. In 1993, he was appointed full professor at the university of Geneva, where he chairs the department of Genetics and Evolution ever since 1997. In 2001, he chaired the national center of research Frontiers in Genetics and in 2012 the division III of the SNSF. In 2006, he was appointed full professor at the federal institute of technology (EPFL) in Lausanne, where he leads the laboratory of Developmental Genomics (UpDUB).
His research activities are in the fields of embryology, genetics and developmental genomics of mammals, in an evolutionnary context. In particular, his laboratory has been closely associated with the structural and functional studies of mammalian Hox genes, by using mouse molecular genetic approaches. Duboule is also active in the communication of science, is member of the Academia Europea as well as of several academies in Switzerland, France and the Netherland. He is a foreign member of the Royal Society (UK) and of the National Academy of Sciences USA. He has received various scientific prizes and awards, amongst which the Marcel Benoist Prize, the Louis-Jeantet prize for medicine in 1998 or the international INSERM prize in 2010 (see also https://en.wikipedia.org/wiki/Denis_Duboule).
Henry Markram
Henry 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.
Melanie Blokesch
Melanie Blokesch holds a PhD degree from the Ludwig-Maximilians-Universität in Munich, Germany. After a postdoctoral stay at Stanford University (USA; Department of Microbiology and Immunology) she joined EPFL as a tenure-track Assistant Professor in 2009 and was promoted to Associate Professor (tenured) in 2016. In 2018, Melanie Blokesch was nominated as new member of the the Swiss National Science Foundation (SNSF) National Research Council (starting date: April 2019). Melanie Blokesch is also an elected member of the European Academy of Microbiology (EAM; since 2018) and the European Molecular Biology Organization (EMBO; since 2019). Among other awards and grants, Melanie Blokesch has been honored with the Prize for Junior Scientists of the German National Academy of Sciences Leopoldina in 2005, an ERC Starting Grant in 2012, the EPFL teaching award "Polysphère" for best teacher in the School of Life Sciences (academic year 2014-2015), the Research Award by the Association for General and Applied Microbiology (VAAM; Germany) in 2015, and an ERC Consolidator Grant in 2016. In 2017, Melanie Blokesch was awarded a Howard Hughes Medical Institute (HHMI) International Research Scholarship.