Day 1 :
Max Planck Institute for Molecular Genetics, Germany
Time : 09:45-10:15
Hans Lehrach has studied Chemistry in Vienna and obtained his PhD at the Max Planck Institute for Experimental Medicine and the MPI for Biophysical Chemistry in 1974. He then moved on to Harvard University, Boston (1974-1978) and then became Group Leader at EMBL, Heidelberg (1978-1987). He has then joined the Imperial Cancer Research Fund, London (1987-1994) as a Head of the Genome Analysis Department. In 1994, he has returned to Germany to become Director at the MPI for Molecular Genetics. He has founded several biotechnology companies such as Sequana Therapeutics, GPC Biotech, Scienion, [email protected], PSF Biotech and Atlas Biolabs. He is the Founder of the Berlin-based company Alacris Theranostics GmbH, specializing in the development of new approaches for personalized medicine for cancer patient diagnosis, treatment and drug stratification. In 2010, he has founded the non-for-profit research institute Dahlem Centre for Genome Research and Medical Systems Biology.
Every patient is different. In particular, every tumor is different. Even subgroups of tumor cells can react differently to specific therapies, due to the heterogeneity of many tumors. Drug therapies therefore typically only help a fraction of patients; many patients do not respond with some suffering sometimes severe side effects of ineffective treatments. The ability to identify effects and possible side effects of different drugs on individual patients will, in our view, require highly detailed molecular analyses of every individual patient and his/her individual disease; data that is integral to generating individualized computer models, which can then be used to test the effects of drugs (or other therapies) on the individual. This will, on one hand, provide a basis for a truly personalized selection of therapies optimal for the individual patient, first in cancer patients but increasingly also in other areas of medicine and prevention. It will, however, also open the way to an increasing virtualization of the drug development process, by e.g., virtual clinical trials of drug candidates carried out throughout the development process.
Imperial College London, UK
Keynote: The retinoic acid receptor controls the mechanobiology in pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion
Time : 10:15-10:45
Armando Del Rio Hernandez obtained his PhD in Chemistry from the Computense University in Madrid. Following this, he completed a period of Postdoctoral training in the US. He worked at Columbia University of New York as a Research Fellow first, and as a Research Associate, later. He currently leads the Cellular and Molecular Biomechanics group in the Department of Bioengineering at Imperial College London. He is a European Research Council Fellow and Editorial Board Member of several journals.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a 5-year survival rate of less than 4%. This rate has remained unchanged for the last 40 years despite advances in conventional therapies targeting cancer cells. PDAC tumours are characterised by remarkable matrix stiffness, and a strong desmoplastic reaction that is mediated by the main cellular component in the tumour microenvironment – pancreatic stellate cells (PSCs). Activated PSCs cross-talk with cancer cells to promote tumour growth, metastasis and chemoresistance, but the molecular mechanism that keeps PSCs persistently activated remains unknown. Our studies implicate retinoic acid receptor as a regulator of traction forces and mechanosensing in PSCs, and this regulation influences the capacity of PSCs to migrate, to remodel the extracellular matrix (ECM), and to promote pancreatic cancer cell invasion.
Max Planck Institute for Biophysical Chemistry, Germany
Time : 11:00- 11:30
Reinhard Luhrmann studied doctorate with Prof. Gassen from University of Münster (1973-1975), postdoctoral fellow with Prof. H. G. Wittmann at the MPI for Molecular Genetics, Berlin (1976-1980), Leader of a Max Planck junior research group, habilitation in Biochemistry and Molecular Biology Free University Berlin (1982), Professor for Physiological Chemistry and Molecular Biology Univ. Marburg (1988-1999), Director and Scientific Member at the MPI for Biophysical Chemistry, honorary professor at the Universities of Göttingen and Marburg. Numerous scientific prizes, among them the Max Planck Research Prize (1990), the Gottfried Wilhelm Leibniz Prize (1996), the Feldberg Prize (2002), and the Ernst Jung Prize for Medicine (2003).
The spliceosome catalyses the removal of the intron from nuclear pre-mRNAs and assembles initially into a pre-catalytic ensemble, termed complex B, which contains the snRNPs U1, U2 and the U4/U6.U5 tri-snRNP and numerous non-snRNP proteins. For catalytic activation the spliceosome undergoes a major structural rearrangement, mediated by the Brr2 RNA helicase, yielding the activated spliceosome (Bact complex). The final catalytic activation of the spliceosome requires an additional restructuring step by the RNA helicase Prp2. Using cryo electron microscopy we have investigated the 3D structure of the human U4/U6. U5 tri-snRNP complex and the yeast activated spliceosome. Our tri-snRNP model reveals how the spatial organization of Brr2 RNA helicase prevents premature U4/U6 RNA unwinding in isolated human tri-snRNPs and how the Sad1 protein likely tethers Brr2 to its pre-activation position. The structure of the yeast Bact complex reveals how the first step reactants (i.e., the 5' splice site and the branch site adenosine) are sequestered by protein prior to catalysis and provide insights into the molecular remodeling events that must be facilitated by Prp2 in order to generate a catalytically active spliceosome. In addition, comparison of the Bact spatial organization with the cryo-EM structures of the tri-snRNP reveal how many spliceosomal components are rearranged during activation of the spliceosome.
Helmholtz Centre for Infection Research, Germany
Time : 11:30- 12:00
Mark Bronstrup has studied chemistry and obtained his PhD from the TU Berlin in 1999. He has joined Aventis in 2000 and spent a research sabbatical with S. P. Gygi at Harvard Medical School in 2003. Between 2005 and 2010, he was leading the Natural Products Science section at Sanofi Aventis in Frankfurt. Between 2010 and 2013, he was managing sections dealing with biomarkers, bioimaging & biological assays. Since December 2013, he has been Head of the Chemical Biology Department at the Helmholtz Centre for Infection Research in Braunschweig and W3 Professor at the University of Hannover. His research is focused on the discovery, the characterization and the optimization of novel anti-infective drugs.
Our efforts to generate novel antibacterial and antiviral lead substances through chemical biology methods will be highlighted through two projects. Infections caused by pathogenic bacteria represent a major health threat that is expected to rise further in the future. The need for novel antibiotics is currently not met by R&D efforts, in particular in the area of infections caused by Gram-negative bacteria. A main scientific hurdle is the lack of understanding how to assure a sufficient translocation of bioactive molecules across the Gram-negative cell wall. In the talk, our efforts to induce an active transport of small molecules into Gram negative bacteria and methods to quantify such uptake will be presented. We report a series of theranostics agents based on DOTAM derivatives comprising siderophores that actively target bacteria, inhibit bacterial growth and demonstrate efficacy to visualize bacterial infections in mice by optical imaging in vivo. In addition, two orthogonal approaches to quantify the intracellular accumulation of such conjugates will be presented. In the second part of the talk, two antiviral natural products with broad-spectrum action against multiple human pathogenic viruses will be presented. Broad spectrum antiviral agents have the potential to improve health-care of infected individuals including patients infected with emerging viruses against which no directly acting antiviral drug is yet available, patients co-infected with two or more viruses and patients infected with viruses that have developed resistance to standard antiviral treatment. Both lead compounds interfere with extra and intracellular lipid metabolism pathways utilized by different viruses.