Life Sciences Seminars
The Life Sciences Seminars are organised monthly by the Master's programmes. The seminars are given by well-known, international scientists who present their research on topics covering the full range of biomedical and life sciences. Information about dates, locations and speakers can be found below.
Life Sciences Seminars 2012 - 2013:
(The LS seminars are planned every third thursday of the month, 16:00h)
- 20 September 2012 - Xtrack
- 18 October 2012 - Toxicology and Environmental Health
- 15 November 2012 - Infection and Immunity
- 20 December 2012 - Environmental Biology
- 17 January 2013 - Biology of Disease
- 21 February 2013 - Regenerative Medicine and Technology
- 21 March 2013 - Neuroscience and Cognition
- 18 April 2013 - Cancer Genomics and Developmental Biology
- 16 May 2013 - Drug Innovation
- 20 June 2013 - Epidemiology
May 16th 2013 – Drug Innovation "Developing a new drug for a neglected disease: A Rocky Road"
Location: Blue lecture Hall, UMC Utrecht
Dr. Koen Andries
Janssen Infectious Diseases & Vaccines, Beerse, Belgium
Tuberculosis (TB) is still one of the world's deadliest diseases, killing 1.4 million people in 2011. The emergence of HIV/AIDS in developing countries where TB was already endemic set up a perfect storm. The deadly synergy between HIV/AIDS and TB (1 in 4 HIV-related deaths is caused by TB), as well as the increasing problem of Multi-Drug resistance (MDR-TB) result in a public health crisis that is spiraling out of control. People with MDR-TB are forced to take up to 20 pills a day with excruciating side effects that range from deafness to nausea and psychosis – to have a 50 % chance of surviving the infection. At the very end of 2012, the US Food and Drug Administration approved bedaquiline, the first dedicated new TB drug since 1963. The story of its discovery and development is an illustration of the challenges one needs to overcome to achieve better treatments for patients around the world.
Dr. Koen Andries obtained his PhD in Veterinary Sciences at the University of Ghent, Belgium. After spending a few years at the Veterinary Faculty, he joined the team of Dr. Paul Janssen in Janssen Pharmaceutica to initiate antimicrobial research. Using cell-based assays (“rational screening”), his team discovered nanomolar inhibitors of uncoating of rhinoviruses (R77975 - pirodavir), picomolar inhibitors of fusion of respiratory syncytial virus (R170591) and, in close collaboration with Dr. Pauwels who later founded Tibotec, several non-nucleoside reverse transcriptase inhibitors of HIV [TIBO’s, alpha-APA’s, and DAPY’s such as R165335/TMC125 (intelence - approved) and R278474/TMC278 (rilpivirine – approved)]. Dr. Andries also led the team that discovered R207910/TMC207 (bedaquiline – approved), the most promising new anti-tuberculosis drug of the TB pipeline, and its unique mechanism of action. He is currently Distinguished Research Fellow at Janssen and part of the team developing bedaquiline. Until last year, he was also teaching Veterinary Microbiology at the University of Antwerp.
MORE INFORMATION: LinkedIn profile Koen Andries or Wikipedia
R. Pauwels, K. Andries, J. Desmyter, D. Schols, M.J. Kukla, H.J. Breslin, A. Raeymaekers, J. Van Gelder, R. Woestenborghs, J. Heykants, K. Schellekens, M.A.C. Janssen, E. De Clercq, P.A.J. Janssen. Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives. Nature, 1990, 343:470-474
K. Andries, B. Dewindt, J. Snoeks, R. Willebrords, K. Van Eemeren, R. Stokbroekx, and P.A.J. Janssen. In Vitro Activity of Pirodavir (R 77975), a Substituted Phenoxy-Pyridazinamine with Broad-Spectrum Antipicornaviral Activity. Antimicrobial Agents & Chemotherapy, 1992, 36 : 100-107.
K Andries, M Moeremans, T Gevers, R Willebrords, C Sommen, J Lacrampe, F Janssens, PR Wyde. Substituted Benzimidazoles with nanoMolar activity against Respiratory Syncytial Virus. Antiviral Research, 60, 209-219, 2003
Koen Andries, Hilde Azijn, Theo Thielemans, Donald Ludovici, Michael Kukla, Jan Heeres, Paul Janssen, Bart De Corte, Johan Vingerhoets, Rudi Pauwels, Marie-Pierre de Béthune TMC125, a novel broad spectrum non-nucleoside reverse transcriptase inhibitor active against non-nucleoside reverse transcriptase inhibitor resistant HIV-1. Antimicrobial Agents & Chemotherapy, 48:4680-6, 2004
Koen Andries, Peter Verhasselt, Jerome Guillemont, Hinrich WH Göhlmann, Jean-Marc Neefs, Hans Winkler, Jef Van Gestel, Philip Timmerman, Min Zhu, Ennis Lee, Peter Williams, Didier de Chaffoy, Emma Huitric, Sven Hoffner, Emmanuelle Cambau, Chantal Truffot-Pernot, Nacer Lounis, Vincent Jarlier. A diarylquinoline drug (TMC207) active on the ATP synthase of Mycobacterium tuberculosis. Science, 2005, 307:223-7
Andreas H. Diacon, Alexander Pym, Martin Grobusch, Ramonde Patientia, Roxana Rustomjee, Liesl Page-Shipp, Christoffel Pistorius, Rene Krause, Mampedi Bogoshi, Gavin Churchyard, Amour Venter, Jenny Allen, Juan Carlos Palomino, Tine De Marez, Rolf P.G. van Heeswijk,Nacer Lounis, Paul Meyvisch, J. Verbeeck, Karel de Beule, Koen Andries, David F. McNeeley A Phase II randomized, placebo-controlled trial of TMC207, an inhibitor of mycobacterial ATP-synthase, in multidrug-resistant pulmonary tuberculosis. New England Journal of Medicine, 2009, 360:2397-2405
Anil Koul, Eric Arnoult, Nacer Lounis, Jerome Guillemont & Koen Andries
The challenge of new drug discovery for tuberculosis. Nature 2011, 469:483-490
April 18th 2013 - Cancer Genomics and Developmental Biology "Guiding signals for enzyme complexes"
Location: Blue lecture hall, UMC Utrecht
John D. Scott
Howard Hughes Medical Institute,
Department of Pharmacology,
University of Washington, Seattle, WA USA
Intracellular signal transduction events are precisely regulated in space and time. This is achieved in part by A-Kinase Anchoring Proteins (AKAPs) that tether signaling enzymes such as protein kinases and phosphatases in proximity to selected substrates. AKAP targeting provides an efficient means to reversibly control the phosphorylation status of key substrates and contributes to the dynamic regulation of sophisticated cellular events. Using a variety of genetic, electrophysiological and live-cell imaging techniques we show that AKAPs, which enhance the precision of signaling events, are up-regulated under certain pathophysiological states. This leads to aberrant regulation of certain physiological processes and disorders such as diabetes and heart disease.
MORE INFORMATION: Link to website John D. Scott
March 21st 2013 - Neuroscience and Cognition "Varieties of extracorporeal awareness: from phantom limb to phantom self"
Location: Blue lecture hall, UMC Utrecht
Professor Peter Brugger
Department of Neurology
University Hospital Zurich, Switzerland
Phantom limbs after amputation have been taken as the perceptual correlate of cortical reorganization after peripheral loss. Yet, phantoms also occur in a minority of people born without a limb, and the challenging question is whether some components of corporeal awareness might be innate. Phantom phenomena are also reported after spinal cord injury and (sub)cortical lesions, i.e. without the physical loss of a limb. Even one’s own entire body may be experienced as a phantom, such as in autoscopic hallucinations or out-of-body experiences. This talk reviews all these special kinds of phantom experiences and emphasizes their importance for theories of “the self” and its bodily basis.
MORE INFORMATION: link to website prof. Brugger
February 21st 2013 - Regenerative Medicine and Technology
Location: Blue lecture hall, UMC Utrecht
Professor Clemens A. van Blitterswijk
Department of Tissue Regeneration
Faculty of Science and Technology, University of Twente
Since the introduction of the term Tissue Engineering the field has grown impressively both as regards the number of involved researchers, disciplines and output in the form of papers, patents etc. In spite of this, the actual successes in the form of e.g. clinical and commercial applications are still lagging behind expectations. There may be many reasons underlying this phenomenon and among those we certainly find an initial underestimation of the complexity of the field. However, even as we currently better realize the fundamental challenges of our field the mere acceptance of these challenges will not solve the issue. In order to overcome the fundamental hurdles that stand at the basis of our field it will be essential to develop novel technologies and/or strategies upon which we can build future successes and at a faster rate as done previously.
After roughly a decade of efforts to generate effective tissue engineering therapies in the field of musculoskeletal regeneration/repair our group concluded that conventional tissue engineering methodologies would not suffice to achieve the results that we had set as a goal for ourselves. Largely, these conventional methodologies were based on an assumption that success would automatically follow from a fundamental understanding of the associated elements like for instance cell behavior and material aspects and, when these were lacking, by adapting protocols previously developed for similar applications. In reality it turns out that this approach, although it follows a conventional scientific way of thinking, might not be the most optimal approach to move forward in our field. Time and time again we and others would discover that what looked promising in vitro would either not work in vivo or through completely different mechanisms than originally foreseen. As it turns out the complex interactions between intracellular pathways, between cells, tissues and organs and our scaffolds at the macro, meso, micro and nano level seem fundamentally unpredictable, with only few exceptions. To this we may add that the scientific methods that we apply are inherently slow. Typically one will test a few formulations or protocols in vitro, will then select the best and move on to further in vivo screening in small experimental animals followed by functionality testing in large animals in order to end in human trials. This method easily takes a decade, if successful. If anywhere in this trajectory the system fails we start all over again.
We are of the opinion that this conventional system is inefficient in several ways. First of all it underestimates the severe variation in response to our hybrid constructs that we encounter between the various species that we use, both from purely physicochemical properties (like size) and genetic interspecies differences but also related to the frequently underestimated distinct variation between individuals. Although this latter aspect is less prominent in, our frequently inbred, experimental animals, it is hard reality in our human recipients. Secondly, as we start the process with few experimental variations in combination with an incomplete, at best, understanding of the systems we apply or work with we are bound to end up with suboptimal technologies, even when successful.
Currently, we are trying to deal with this in our lab while developing a new technology toolbox that might, at least partially overcome, the above issues. The platform is based on four pilars. First we use high throughput assessment of biologically active agents for our cells as is common in drug discovery. As big pharma, with a frequently much better biological fundamental knowledge base, is forced in this direction it is bound to be usefull in our much smaller field with technologically more complex applications. Although, the hit compounds may still fail in the following process, at least we will now be testing the most powerful among many instead of the best of few. Second, as our systems are so complex we will frequently have to use multiple compounds simultaneously. As these tend to interact, routine lab protocols will not suffice to obtain the optimal combination of factors which is why we now invest in lab on a chip platforms to allow the testing of multifactorial combinations in the shape of multiplex arrays. Third, as we see the rise of instructive, smart, scaffolds and/or materials and also here lack most of the fundamental knowledge on the driving mechanism(s) we have implemented array technology to assess the instructive abilities of libraries with millions of surface topographies in an approach referred to as materiomics. Finally in order to overcome the uncertainties and limitations of animal experimentation we have embarked on developing platforms that allow us to generate complex tissues in the meso to macro range in highthroughput version. In addition this approach will create possibilities to assemble such microtissues into larger structure which may mimic the complex structure of organs or parts thereof.
The combination of the above technologioes will now offer us a toolbox that is better fit for dealing with tissue engeering complexity than most conventional techniques applied today.
MORE INFORMATION about prof. van Blitterswijk can be found in this document.
January 17th 2013 - Biology of Disease "The antiphospholipid syndrome"
Location: Blue lecture Hall, UMC Utrecht
Professor Philip de Groot
Department of Haematology
UMC Utrecht, the Netherlands
Autoimmunity is the failure of an organism to identify its own constituents as self. This will result in an immune response against its own cells or proteins. Autoimmune diseases can be divided into systemic and localized or organ-specific autoimmune disorders. There are a number of systemic auto-immune diseases that affects blood coagulation and individuals with certain forms of auto-immunity often present themselves for the first time with thrombotic or bleeding complications. Examples are the anti-phospholipid syndrome (APS), heparin induced thrombocytopenia, and thrombotic thrombocytopenic purpura.
The antiphospholipid syndrome is an auto-immune disease characterized by thrombotic complications in both arteries and veins as well as fetal losses in combination with the presence of so-called antiphospholipid antibodies in plasma of these patients. It is now generally accepted that these auto-antibodies are not directed against negatively charged phospholipids but towards plasma proteins bound to these phospholipids. The most prominent antigen in APS is β2-Glycoprotein I (β2-GPI), a plasma protein with affinity towards anionic phospholipids. APS is an intriguing syndrome because we have difficulties to comprehend how the presence of auto-antibodies against β2-glycoprotein I increases the risk for thrombosis and fetal loss. β2-Glycoprotein I is a plasma protein without a clear function and individuals without this protein seem to be completely healthy. Moreover, the most relevant assay that we use to detect the presence of auto-antibodies against β2-glycoprotein I, a prolongation of a clotting assay named Lupus anticoagulant, express an opposite effect on coagulation as expected for a thrombotic risk. Prolongation of clotting assays points to a bleeding tendency, not a thrombotic tendency. Both the target of the auto-antibodies, β2-Glycoprotein I, and the detection method, lupus anticoagulant, do not give us a lead to the mechanism behind the increased thrombotic risk. Nevertheless, mouse models in which auto-antibodies against β2-glycoprotein I isolated from patients were used show abundantly clear that these auto-antibodies are the cause of the increased risk for thrombotic manifestations and pregnancy morbidity.
In the present lecture I will introduce the coagulation system, why it is so important and explain how the antiphospholipid antibodies defy our classic knowledge of blood clotting. I will conclude my talk with possible explanations why individuals with these auto-antibodies in their blood have such a high risk of severe thrombotic complications at a younger age.
de Groot PG, Urbanus RT. (2012) The significance of auto-antibodies against β2-Glycoprotein I. Blood 120: 266-74
de Groot PG, Meijers JC. (2011) β2-Glycoprotein I: evolution, structure and function. Journal of Thrombosis & Haemostasis 9: 1275-1284.
Tripodi A, de Groot PG, Pengo V. (2011) Antiphospholipid syndrome: laboratory detection, mechanisms of action and treatment. Journal of Internal Medicine 270:110-22.
MORE INFORMATION can be found in this document.
December 20th 2012 - Environmental Biology "Ecogenomics goes underground"
Location: Blue lecture Hall, UMC Utrecht
Professor George Kowalchuk
Netherlands Institute for Ecology
Wageningen, the Netherlands
Microbes dominate our planet. They are the most abundant and diverse organisms on Earth, and their activities drive the functioning of virtually all ecosystems, including soils. Plant-microbe interactions are central to the dynamics of terrestrial ecosystems, with plants providing the primary carbon and energy inputs and microbes being responsible for the delivery and recycling of nutrients and organic substrates. However, due to human influences such as land-use change and anthropogenic impacts on climate, these interactions and the processes that they drive are coming under increased pressure. Numerous advances in microbial ecology are now allowing us to shed light into the black box of soil-borne microbial communities and plant-microbe interactions, providing us the opportunity to examine the impacts of environmental changes on microbial ecosystem motors. In this presentation, I will highlight a number of recent studies dedicated to improving our understanding of how land use and climate changes influence soil-borne microbial communities and the consequences of these changes on ecosystem dynamics and feedbacks to climate. Special attention will be paid to impacts on plant-microbe interactions and the importance of scale in studying the diversity and functioning of microbes in soil.
November 15th 2012 - Infection and Immunity "The placebo response: A model for neuroscience and a tool to mediate immune responses"
Location: Blue lecture Hall, UMC Utrecht
Professor Manfred Schedlowski
Institute of Medical Psychology and Behavioral Immunobiology,
Medical Faculty, University of Duisburg-Essen, Germany
In modern medicine, the placebo response has often been regarded as a nuisance in basic and particularly in clinical research. The latest scientific evidence has demonstrated, however, that the placebo effect stem from highly active processes in the brain that are mediated by psychological mechanisms such as expectation and conditioning. These processes have been described in some detail for many diseases and treatments, demonstrating that they can represent both strength and vulnerability in the course of a disease as well as in the response to a therapy.
Manfred Schedlowski is Professor and Director of the Institute of Medical Psychology and Behavioral Immunobiology at the Medical Faculty, University of Duisburg-Essen, Germany. Born 1957 in Hannover, Germany, he obtained his degree in Psychology and his PhD at the Department of Medical Psychology, Hannover Medical School, Germany. Since October 1997, Manfred Schedlowski is Full Professor and Director of the Institute of Medical Psychology and Behavioral Immunobiology at the Medical Faculty, University Essen-Duisburg interrupted by a research stay as Professor of Psychology and Behavioral Immunobiology at the Swiss Federal Institute of Technology (ETH) in Zürich, Switzerland (2004-2007).
Manfred Schedlowski’s current primary focus of research is the neurobiology of placebo responses, in particular the mechanisms and clinical relevance of behavioral or Pavlovian conditioning of immune functions.
October 18th 2012 - Toxicology and Environmental Health "Reproductive Toxicology: of Mice and Man and Molecules"
Location: Blue Lecture Hall, UMC Utrecht
Professor Aldert H. Piersma
RIVM Center for Health Protection, Bilthoven, the Netherlands
Reproductive toxicology has developed as a significant branch of toxicological research after the thalidomide tragedy in the early sixties indicated the vulnerability of the unborn child to external exposures. Since the eighties, hazard and risk assessment of chemicals and drugs for reproduction and embryo-foetal development has been based on globally harmonized animal study protocols. Public awareness as well as novel legislation such as the cosmetics regulation and REACH in the EU has stimulated significant initiatives towards the development and introduction of alternative methods for hazard identification, aimed at the reduction of animal use. Embryo-, organ- and cell culture techniques have emerged, and their coupling with modern molecular biology technologies now allow in depth mechanistic analysis of the adverse effect pathways of chemicals and drugs. The intrinsic reductionist nature of alternatives, and uncertainties about applicability domain and predictability have hampered their implementation in regulatory toxicology. On the other hand, the elaborate mechanistic information provided by alternative methods may allow improved extrapolation for estimation of human hazard than the classical apical studies in animal species can provide. Among the currently most promising and popular alternatives for developmental toxicity testing are the rat postimplantation whole embryo culture, the zebrafish embryotoxicity assay, and the embryonic stem cell test. We have applied transcriptomics to provide a genome wide assessment of effects of test compounds on gene expression. Compound class-specific gene expression signatures could be derived, and concentration-response analysis revealed distinct sensitivities of different gene sets, providing mechanistic information on compound effects. Comparison of gene expression responses between alternative tests and animal studies allowed phenotypic anchoring, providing evidence that gene expression responses in vitro were relevant in vivo. In spite of significant progress in this area, crucial questions remain. They include the issue of defining threshold of adversity in vitro and the identification adverse outcome pathways. The latter should ultimately lead to optimal biomarker sets for in vitro identification of toxicity.
Aldert H. Piersma PhD is a Reproductive Toxicologist employed as a senior scientist at the RIVM Center for Health Protection in Bilthoven, the Netherlands. After his PhD on hematopoiesis (1985) he joined the Hubrecht Laboratory for developmental biology, and was subsequently appointed at RIVM (1988) as a reproductive toxicologist. Since then he leads the reproductive toxicology research group at RIVM. His work is dedicated to research and advice aimed at improving hazard and risk assessment in the area of reproductive toxicology. This includes the development and implementation of alternative methods, enhancing the efficiency of animal study protocols, defining innovative testing strategies, and promoting their implementation in regulatory toxicology. He is and has been a member of a series of (inter)national committees and working groups. He is associate editor of the journal Reproductive Toxicology and a past president of the European Teratology Society.
September 20th 2012 - Xtrack Symposium 2012 “A walk down memory lane!”
Location: Megaron Lecture Hall, Educatorium, Uithof
Time: 13:00 - 18:00h
The topic of this year's symposium is Memory, and has the fitting name 'A Walk Down Memory Lane'. Five speakers will address several aspects of memory during the afternoon. Albert Postma (UU) will give a short introduction on general principles of memory. Following this, Marcel van den Hout (UU) will provide a lecture about Eye Movement Desensitization and Reprocessing (EMDR), which is a revolutionary way to treat patients suffering from traumatising memories. Then, Jan Born (University of Tübingen) will provide a lecture about sleep and memory with the entitlement 'Sleep's critical role for memory'. During our third lecture, Michael Kopelman (King's College London) will talk about the fascinating aspects of confabulation, also known as false memories, and its presence in patients with several kinds of memory disorders. At last, Marian Joëls (UU) will close the afternoon with a lecture that provides us with insight in the relationship between stress and memory. Might 'Stress be a blessing in disguise'? You will find the answer on this question during the afternoon at the 20th of September.
More information: Programme Xtrack 2012, flyer Xtrack 2012, and www.xtrack2012.com