NovAliX Conference 2013 Biophysics in Drug Discovery
Developing the Synergy between Biophysics and Medicinal Chemistry to Deliver Better Drugs
Strasbourg, France October 15-18, 2013
KN01 - Biophysical Methods and Fragment Based Drug Discovery: Targeting Protein-Protein Interactions in Cell Regulatory Systems
Prof. Sir Tom BLUNDELL
UNIVERSITY OF CAMBRIDGE, Cambridge, United Kingdom Read more
Prof. Sir Tom BLUNDELL
Sir Tom Blundell FRS, FMedSci
University of Cambridge
1. Research interests in the molecular architecture of living organisms have been focused on molecular and structural biology of growth factors, receptor activation, signal transduction and DNA repair, important in cancer and other diseases. Tom Blundell has characterised the roles of multiprotein assemblies in achieving high signal-to-noise in cell regulatory and signalling systems. He also has developed extensive software, pioneering knowledge-based approaches for structural bioinformatics that are used worldwide in academia and in the biotech and pharmaceutical industries. He has developed new approaches to exploring biological and chemical space for target selection and lead discovery in the development of candidate drugs. He has published over 500 research papers, including 30 in Nature and Science.
1964 BA in Natural Sciences;
1967 D.Phil. Oxford University;
1973 Lecturer, Biological Sciences, Sussex University;
1976-1996 Professor of Crystallography, Birkbeck College, London;
1991-96 Chief Executive Officer, AFRC; Founding CEO, BBSRC;
1996 - 2009 William Dunn Professor and Head of Biochemistry, University of Cambridge;
2003- 2009 Head, School of Biological Sciences, Cambridge;
2009-2016, Director of Research; Emeritus Professor Biochemistry, Cambridge;
2. Honours 1984 FRS; 1985 Member of EMBO; 1986 Alcon Award; 1987 Gold Medal, Institute Biotechnology; 1987 Krebs Medal, FEBS; 1988 Ciba Medal, Biochemical Society; 1988 Feldberg Prize in Biology and Medicine; 1993 Member Academia Europaea; 1995 Fellow, Indian National Science Academy; 1996 Gold Medal, Society for Chemical Industry; 1997 Knighthood; 1998 First Recipient, Pfizer European Prize for Innovation; 1998 Bernal Medal, Royal Society; 1999 Founding Member, Academy of Medical Sciences; 2005-2008 President UK Biosciences Federation; 2006 Hon Memb, British Biophysical Society; 2006 Honorary Fellow Royal Society Chemistry; 2008 Foreign Member, Third World Academy of Sciences; 2008 Ramachandran Professor, IISc Bangalore; 2009-2011 President, Biochemical Society; Honorary Fellow. 2011 Foreign Member Chilean Academy of Sciences. 2011 President, UK Science Council; 2012 Honorary Fellow, Society of Biology
3. Industry: companies founded, boards etc Astex Therapeutics: Co-founder, 1999, Board Member, Chair SAB 1999-2011; Biofabrika: Co-founder, 1989 – 1991; Celltech: Non-executive Director, 1996-2004; Chair SAB, 1998- 2004; UCB Celltech, Science Advisory Board, 2005; SmithKline Beecham: International R&D Board, 1997-1999; Pfizer: Consultant in UK and USA, 1983-1990; Parke Davis: US Consultant, 1987-1990; Abingworth Management Ltd, Science Advisory Board, 1986-1990, 1996-; Syntaxin: member of SAB; FEI: SAB 2007-2010; Isogenica, Scientific Consultant, 2008 -
4. Public Bodies: Research Councils: AFRC Council (1985-1990); DG, (1991-1994); BBSRC Founding CEO, BBSRC, 1994-1996. Non-executive Chairman of BBSRC: 2009 - Royal Commission on Environmental Pollution, Chairman (1998-2005); Advisory Council on Science and Technology (ACOST) Cabinet Office (1988-1990).
PL04 - Protein Methyltransferase Inhibitors as Personalised Cancer Therapeutics: DOT1L and EPZ-5676
Ann Boriack-Sjodin was first introduced to the field of crystallography during her undergraduate studies at Harvey Mudd College. She received her PhD in Biological Chemistry at the University of Pennsylvania under the direction of Dr. David Christianson where she studied carbonic anhydrase isozymes II and V to understand the dependence of structural features on catalytic activity. She was a postdoctoral fellow in the laboratory of Dr. John Kuriyan at The Rockefeller University where she solved the structure of the complex of Ras and SOS to understand the structural basis of Ras activation. She has spent her industrial career using protein crystallography and other biophysical methods to progress drug discovery programs in a variety of therapeutic areas, first at Biogen Idec and then at AstraZeneca. She joined Epizyme in the fall of 2012 and is currently the Director of Protein and Structural Sciences where she is applying her knowledge and expertise in drug discovery to the protein methyltransferase family of enzymes.
PL08 - Backscattering Interferometry: An Enabling Drug Development Technology
Dr Darryl BORNHOP
VANDERBILT UNIVERSITY, Nashville, United States Read more
Dr Darryl BORNHOP
Dr. Darryl J. Bornhop is currently Professor of Chemistry at Vanderbilt University and a core member of the Vanderbilt Institute for Chemical Biology and the Vanderbilt-Ingram Cancer Center. His research is highly inter-disciplinary merging Nanoscale Sensing and Chemical Biology to address currently intractable scientific problems. Dr. Bornhop received his B.S. in chemistry and his M.A. in environmental chemistry from the University of Missouri in Columbia. He earned his Ph.D. in Analytical Chemistry under the direction of Dr. Norman J. Dovichi, at the University of Wyoming and the University of Alberta. In 1994, after working in the private sector in a variety of capacities from principal scientist at Spectra Physics Inc. to Vice President for R&D at MediVisions Inc., he joined the faculty at Texas Tech University becoming Professor of Chemistry and Biochemistry in 2002 and Research Professor at the Southwest Cancer Center, before joining the faculty of Vanderbilt University in 2003.
KN03 - Combining X-Ray Crystallography and Single-Molecule Methods to Probe Antibiotic Inhibition of Translation
Prof. Jamie CATE
UNIVERSITY OF CALIFORNIA, Berkeley, United States Read more
Prof. Jamie CATE
Jamie H. Doudna Cate, Professor
University of California, Berkeley
Departments of Chemistry and Molecular and Cell Biology
Structural biology and biophysics of protein synthesis
Ph.D. Yale University, Dept. of Molecular Biophysics and Biochemistry
2011+ Professor, University of California, Berkeley
2001–2011 Assistant and Associate Professor, University of California, Berkeley
1999–2001 Associate Member, Whitehead Institute for Biomedical Research
1999–2001 Assistant Professor of Biology, Massachusetts Institute of Technology
PL02 - Enabling GPCR Drug Discovery Through Structural and Biophysical Insights
Rob obtained his BSc and PhD (Inorganic Chemistry) from the University of Sydney. He then did post-doc studies with Iain Campbell in Dept of Biochemistry at University of Oxford determining solution structures of growth factors by NMR. Rob joined Glaxo to establish protein NMR studies, and while at Glaxo, Glaxo Wellcome and Glaxo Smith Kline he led a number of areas including structural biology & biophysics, protein production, analytical chemistry and biochemistry, and computational chemistry. Rob has also been involved in several external partnerships, including establishing the Structural Genomics Consortium in 2003. Rob joined Heptares Therapeutics in 2011 as Head of Biomolecular Structure, where he is responsible for structural biology and biophysics, computational chemistry and informatics and protein biochemistry, as well as management of external alliances.
PL10 - Application of SPR Biosensors Throughout the Drug Discovery Process
Helena Danielson is Professor of Biochemistry at Uppsala University in Sweden since 2002 and Chief Scientific Officer of Beactica AB. She is a specialist in enzyme-based drug discovery and molecular recognition. Her education includes a Master of Science in Chemical Engineering at Lund University (1982) and, as a Fulbright scholar, a Master of Science in Biochemistry, University of Rochester, Rochester, NY, USA (1984), and a Ph. D. in Biochemistry at Stockholm University (1987). As a postdoc at Karolinska Institutet in Stockholm Helena Danielson started a research project on HIV protease as a drug target for AIDS, and has since expanded her research to other enzymes and diseases, more recently also with an interest in membrane receptors and neurological drug targets. Helena Danielson has focused on developing enzymology for drug discovery, and in particular biomolecular interaction analysis for detailed studies of enzyme-inhibitor interactions and other important recognition processes in the life science area. Helena Danielson co-founded Beactica AB in 2006. The company is a specialist drug discovery company that generates novel drug leads from low molecular weight fragments by integrating biomolecular interaction analysis with in silico molecular docking techniques.
PL07 - Label-Free, Immobilisation-Free Interaction Studies Using Microscale Thermophoresis
Stefan Duhr studied Biochemistry at the University of Witten/Herdecke, Germany with a specialization in Physical-Biochemistry. In 2007 he finished his PhD-Thesis in Physics-Department at Ludwig-Maximilians-University in Munich with the title "Thermo-Optical Molecule Manipulation". In May 2008 he founded NanoTemper Technolgies GmbH, that develops, produces and markets instruments based on the proprietary MicroScale Thermophoresis Technology (MST) for biomolecular interaction studies. Stefan Duhr is Geschaeftsfuehrer (CEO) of NanoTemper.
Matthias is heading the department for Molecular Interaction and Biophysics (MIB) at Merck-Serono. Integrated into the “Small Molecule Platform”, the group is responsible for molecular interaction studies and protein crystallographic work, to generate insight into the mode of action by combining various biophysical methods. Fragment based lead discovery, thermodynamic signatures, interaction kinetics and protein structure are the current data packages which support the drug discovery process at Merck-Serono with biophysics.
Prior to that position, he was responsible for a protein chemistry group working with different biophysical methods combined with the protein purification and analysis for structural studies and high throughput screening campaigns.
Before joining Merck, he was working on protein kinases and their biochemical characterization a post doctoral fellow at the Friedrich Miescher Institute, part of the Novartis Research organisation,. As EMBO fellow he worked on nucleotide exchange factors and adaptor proteins in the p21ras signalling pathway at the CNRS Institute de Pharmacologie Moleculaire et Cellulaire in the technology park of Sophia Antipolis near Nice/ France. He accomplished his doctoral work in the department of Biophysics at the Max Plank Institute in Heidelberg focusing on molecular interaction studies of small p21ras like proteins.
PL01 - Binding of Drug Substances to Molecular Targets Investigated by Biophysical Methods
Dr Michael HENNIG
F. HOFFMANN-LA ROCHE LTD., Villigen, Switzerland Read more
Dr Michael HENNIG
Michael received his PhD in biochemistry and protein crystallography at the EMBL (European Molecular Biology Laboratory) in Hamburg, Germany, and at the Charitè Berlin in 1992. After a postdoctoral fellowship at the Charitè, he joined the Biozentrum, University of Basel, Switzerland, as research assistant. End of 1995, he continued his career in industrial research at F. Hoffmann - La Roche as a lab head for X-ray crystallography. Since 2001 he has been Vice Director for Structure Research at Roche Basel and extended his responsibility with the appointment to the head of Discovery Technologies in 2008. In this function, he is responsible for technologies to support small molecule drug discovery including compound depository, assay development and screening, stem cell research, protein generation as well as analytics. The main research interest is to facilitate early small molecule drug discovery from target assessment & validation to hit & lead identification and optimization methods in various therapeutic areas including metabolic disease and neuroscience. He is lecturer in protein crystallography and pharmacy, author of more than 70 articles and patents and professor in structural biology at the University of Basel.
PL06 - Can we Use Kinetics and Thermodynamics to Guide Drug Discovery?
Dr Geoff HOLDGATE
ASTRAZENECA, Macclesfield, United Kingdom Read more
Dr Geoff HOLDGATE
Geoff undertook a degree in biological and biochemical sciences at the University of Salford starting in 1988. As part of his undergraduate studies Geoff undertook a year in industry and joined the Protein Function team of ICI Pharmaceuticals in 1990. This work involved mechanistic studies on the epidermal growth factor receptor tyrosine kinase, leading to the discovery of a potent inhibitor related to Iressa (trademark of AstraZeneca). Following graduation in 1992, he rejoined ICI as a permanent member of the Protein Function Team. ICI Pharmaceuticals subsequently became Zeneca Pharmaceuticals, which merged with Astra to form AstraZeneca. During the last 21 years Geoff has applied the techniques associated with mechanistic enzymology and biophysics to the study of structure-function relationships on numerous drug targets and associated ligands, including several successful drug discovery projects, such as Iressa, Crestor and Caprelsa (trademarks of AstraZeneca). He currently holds the position of Principal Scientist and Associate Director in Biophysics within the Discovery Sciences Department at AstraZeneca, Alderley Park. He leads a team of 8 scientists whose work involves the identification and characterisation of hit and lead compounds. His work interests include a range of biophysical techniques (including ITC, DSC, SPR), as well as mechanistic enzymology approaches to characterise the mechanism, kinetics and thermodynamics of protein-ligand interactions for exploitation in drug design.
PL09 - Towards Personalised Cancer Medicine with New NMR Tools to Probe Small GTPase Proteins
Christopher Marshall obtained his Ph.D. in Biochemistry from Queen’s University at Kingston, Canada in 2005, and was awarded the CIHR Jean-François St-Denis Fellowship in Cancer Research for postdoctoral studies in cancer structural biology with Mitsu Ikura at Ontario Cancer Institute. Chris is currently a Scientific Associate and Manager of NMR Translational Research at Ontario Cancer Institute/University Health Network in Toronto, Canada. His research focuses on the structure and function of small GTPase proteins, their regulation by GAPs/GEFs, and mechanisms of deregulation in oncogenesis. Chris pioneered the development of a quantitative real-time NMR-based GTPase assay, which has played a key role in elucidating regulatory mechanisms of full-length GAPs/GEFs, and effects of disease-associated mutations in components of small GTPase signaling pathways.
PL11 - Finding Active Ligands to kRAS Using Solution State NMR
Dr Till MAURER
GENENTECH, South San Francisco, United States Read more
Dr Till MAURER
Senior Scientist, Structural Biology Department, Genentech, South San Francisco
Adjunct Professor, Institute for Biophysics and physical Biochemistry, Regensburg University
Observing molecular interaction using NMR spectroscopy
Research scientist, Max-Planck-Institute for medical Research, Heidelberg
Assistant professor, Regensburg University
Senior scientist Boehringer Ingelheim, Biberach/Ingelheim
Principal scientist, Merck KGaA, Darmstadt
PL12 - Biophysics in Pharmaceutical Lead Discovery
Dr Johannes OTTL
NOVARTIS INSTITUTE OF BIOMEDICAL RESEARCH, Basel, Switzerland Read more
Dr Johannes OTTL
Dr. Johannes Ottl is working since 2000 in the lead discovery field at Novartis Institutes for Biomedical Research. Since 2012 he is heading the Screening Sciences Group in the Center for Proteomic Chemistry in Basel, Switzerland and is responsible for new lead discovery approaches and biophysics to study the interactions of drug candidates with target proteins. From 2007-2012 he was heading the Label Free Technologies group and he had responsibility as a lab head for the development and realisation of automated high throughput screening campaigns to identify new drug candidates between 2000 and 2007. From 1999 to 2000 he worked as a post-doctorate in the Combinatorial Chemistry department at Novartis on the multiparallel synthesis of radio tag encoded chemical libraries. He received his Ph.D. in Bioorganic Chemistry at the Max Planck Institute of Biochemistry in Martinsried in 1999 and has studied Chemistry at the Ludwig Maximilians Universitaet in Munich, Germany.
KN02 - Molecular Mechanism of Action (MMOA) in Drug Discovery
David Swinney has over 20 years of industrial experience (Roche, Syntex) working to identify promising leads, clinical candidates and effective mechanisms of drug action to address unmet medical needs. Dave has a PhD in medicinal chemistry from the University of Washington, Seattle, a recognized expertise in binding kinetics and biochemical pharmacology, and is currently at the non-profit Institute for Rare and Neglected Diseases Drug Discovery, aka iRND3, working to identify new drug discovery starting points to address unmet medical needs.
PL05 - Investing in Knowledge: Combining Biophysical Data in Fragment-Based Drug Discovery
Dr Glyn WILLIAMS
ASTEX PHARMACEUTICALS, Cambridge, United Kingdom Read more
Dr Glyn WILLIAMS
Glyn Williams, VP Biophysics, Astex Pharmaceuticals
Glyn obtained his D.Phil. in Chemistry from the University of Oxford and subsequently carried out teaching and research in Bio-Inorganic Chemistry at the University of Sydney and University College London. His interests in Nuclear Magnetic Resonance (NMR) and protein structure took him to Roche Products (UK) in 1990 before joining Astex Pharmaceuticals (then Astex Technology) in 2001 as the Head of Biophysics.
Astex has specialised in fragment-based screening and the elaboration of weakly-bound but highly ligand-efficient, simple molecules into potent clinical candidates. Crystallography and biophysical methods, principally NMR, mass spectrometry and calorimetry, are used extensively at Astex to screen fragments and to measure the affinities of hits for the target. In addition, biophysical data contribute to optimisation of the protein target, the selection of molecules for screening libraries and to the elimination of false-positive hits, even when screening at very high concentrations.
OC09 - Identification and Validation of Small Molecule Inhibitors of G Protein Beta 1 Gamma 2
Dr Preeti BAKRANIA
MRC TECHNOLOGY, London, United Kingdom
OC01 - Biophysical Investigations of the Synergistic Activities of Antimicrobial Peptides: New Strategies to Fight Multiresistance
Prof. Burkhard BECHINGER
UNIVERSITY OF STRASBOURG, Strasbourg, France
OC05 - Bringing Light into Antibody Binding Characteristics in Crude Extracts by Means of FCCS
Dr Frank BECKER
INTANA BIOSCIENCE GMBH, Planegg, Germany
OC04 - Pharmacokinetics and the Drug-Target Residence Time Concept
Dr Göran DAHL
ASTRAZENECA, Mölndal, Sweden
OC02 - X-Ray Crystallography, Kinetic Target-Guided Synthesis and NMR to Unravel the Mode of Action of Insulin Degrading Enzyme Modulators
Prof. Rebecca DEPREZ-POULAIN
UNIVERSITY OF LILLE, Lille, France
OC07 - Binding Rate Constants Measured on Microliter Volume Using On-Chip Temperature Modulation and Fluorescence Lock-In Detection
Dr Charlie GOSSE
CNRS, Marcoussis, France
OC03 - Residence and Recognition Time and their Use for Structure Kinetic Relationships and for Judging Efficacy of Lead Series
Dr Markku HÄMÄLÄINEN
GE HEALTHCARE BIO-SCIENCES, Uppsala, Sweden
OC10 - Fragments at UCB: Implementation of Non-Covalent Mass Spectrometry and 19F NMR as Orthogonal Screening Techniques
Dr Hannah MAPLE
UCB, Slough, United Kingdom
OC06 - Detection and Analysis of Proteins with an Electro-Switchable DNA Chip
Dr Ralf STRASSER
DYNAMIC BIOSENSORS GMBH, Martinsried, Germany
OC08 - CRYO-TEM: The Way to Answer Real Biological Questions through Unraveling the 3D Mechanistics of Protein