Developing the Synergy between Biophysics and Medicinal Chemistry to Deliver Better Drugs
Biophysics in Drug Discovery 2022 | European Edition
Munich, Germany & Virtual May 9-11, 2022
In-cell NMR: a Powerful Approach for Drug Discovery (KL01)
Prof. Lucia BANCI
UNIVERSITY OF FLORENCE, Sesto Fiorentino, Italy Read more
Prof. Lucia BANCI
Lucia Banci is Professor of Chemistry at the University of Florence.
She has an extensive expertise and has provided original contributions and breakthroughs in Structural Biology and in biological NMR. She has addressed and unraveled many aspects of the biology of metal ions in biological systems.
The in cell NMR approach developed by her and her group allows for the detection of human individual proteins in living human cells with atomic level resolution. She also exploited the knowledge of structural biology approaches through NMR expertise to develop an innovative approach to vaccine design, based on the knowledge of the structure of the pathogen antigens and of the interaction pattern with antibodies, to design structure-based vaccines.
She is Director of the Center of Magnetic Resonance (CERM) of the University of Florence, Head of the Italian Core Center of the ESFRI Research Infrastructure Instruct-ERIC, and a member of the Instruct-ERIC Executive Committee and of the Council.
Functionalizing Covalent Binders (IL07)
Dr Nir LONDON
THE WEIZMANN INSTITUTE OF SCIENCE, Rehovot, Israel Read more
Dr Nir LONDON
Dr. Nir London completed his PhD in computational structural biology at the Hebrew University in 2012. He then pursued a post-doctoral fellowship with Brian Shoichet at UCSF where he developed a pioneering virtual screening platform for covalent inhibitor discovery. In 2015 Dr. London joined the Weizmann Institute of Science, where he is currently the Alan and Laraine Fischer Career Development Chair in the Dept. of Chemical and Structural Biology. Dr. London’s lab is focused on covalent chemical biology and drug discovery and is developing new technologies to discover and functionalize covalently acting compounds. His honors include amongst others the Alon fellowship, the EFMC award for young medicinal chemist in academia and the ISCB award for young chemical biologist.
Positioning Biophysics on the Drug Discovery Map (IL05)
Dr. Christine Genick has been working since 2000 in the field of biophysics, not only on the development of technologies for screening, but also in the utilization of these approaches for lead finding in drug discovery. In 2009, Chris joined the Novartis Institutes for Biomedical Research as a laboratory head in charge of designing biophysical strategies for HTS, FBS, and focused screen follow-up. Later she became the Core Biophysics Technology Representative, which entails designing new applications, evaluating technologies, and establishing approaches to detect small molecule binding interactions with target proteins. Currently she is a co-lead on the Advancing Structural Biophysics Infrastructure Project in the Protein Sciences department. In her spare time, she serves as a Scientific Advisory Board member of the MOlecular-Scale Biophysics Research Infrastructure (MOSBRI).
Reactive Fragment Platforms for Covalent Hit ID (IL06)
Dr Emma GRANT
GLAXOSMITHKLINE, Stevenage, United Kingdom Read more
Dr Emma GRANT
Emma conducted her PhD studies on the collaborative programme between the University of Strathclyde and GlaxoSmithKline. Her research primarily focussed on photoaffinity labelling and the development of a reactive fragment screening platform, known as the PhABits, to identify tool compounds for target validation. Since graduating in 2020 and being awarded the SCI Young Chemist in Industry Prize, Emma’s work has focussed on the expansion of reactive fragment screening platforms for covalent drug discovery. She now leads the application of these technologies in covalent hit ID and to assess target tractability in the Chemical Biology group within GSK.
Exploration of Orthogonal E3 Ligases for Targeted Protein Degradation (IL10)
Lena Muenzker is currently a Postdoctoral Fellow at Boehringer Ingelheim RCV GmbH & Co KG in Vienna, Austria, where her work focuses on new E3 ligases and the development of proteolysis-targeting chimeras (PROTACs). She received her PhD as part of the Marie Curie FragNET PhD program under the supervision of Dr. Wolfgang Jahnke and Dr. Andreas Marzinzik in the Chemical Biology and Therapeutics department at Novartis Basel, Switzerland and Prof. Gerhard Klebe at the Philipps-Universität Marburg, Germany. Her work comprised structural biophysics and fragment-based drug discovery to identify novel inhibitors of the Trypanosomal brucei farnesyl pyrophosphate synthase for the treatment of Human African sleeping sickness.
EINDHOVEN UNIVERSITY OF TECHNOLOGY, Eindhoven, The Netherlands Read more
Dr Christian OTTMANN
Christian Ottmann is Associate Professor of Molecular Cell and Structural Biology at the department of Biomedical Engineering (research group Chemical Biology). He works on small-molecule modulation of Protein-Protein Interactions (PPIs) with a special focus on stabilization of 14-3-3 adapter protein PPIs. He is involved in several chemical biology projects on 14-3-3 PPIs important in Alzheimer’s disease, inflammation and cystic fibrosis. In this context he was coordinator of the FP7 Industry-Academia Partnership and Pathways (IAPP) 14-3-3STABS and the Horizon2020 European Training Network (ETN) TASPPI.
From 1999-2003, he did his PhD research at the Eberhard-Karls-University of Tübingen under supervision of Prof. Claudia Oecking and graduated summa cum laude. From 2003-2004, he was a Postdoctoral Research Assistant with Prof. Oecking. In 2006, he became a group leader at the Chemical Genomics Centre (CGC) of the Max Planck Society (Dortmund, Germany). In 2012, Christian Ottmann was appointed Associate Professor of Molecular and Structural Cell Biology at the department of Biomedical Engineering of Eindhoven University of Technology (TU/e). In that same year he was recipient of the Innovation Award in Medicinal/Pharmaceutical Chemistry of the Gesellschaft Deutscher Chemiker and the Deutsche Pharmazeutische Gesellschaft. In 2013, Christian Ottmann received the Young Chemical Biologist Award of the International Chemical Biology Society (ICBS). In 2014 he was appointed professor at the Institute for Organic Chemistry of the University of Duisburg-Essen (Germany). In 2020 he founded Ambagon Therapeutics together with Luc Brunsveld (TU/e) and Michelle Arkin (UCSF) and serves since July 2020 as CTO of this company
Manipulating RNA Function by Structural Dynamics (IL02)
Prof. Katja PETZOLD
KAROLINSKA INSTITUTET, Stockholm, Sweden Read more
Prof. Katja PETZOLD
Katja Petzold was born in Dresden, Eastern Germany, in 1981. She received her Ph.D. in Medical Biophysics from Umeå University, Sweden in 2009, where she started her work on NMR method development for nucleic acids as well as for phospholipids. As researcher at the University of KwaZulu/Natal, Durban, South Africa, she gained experience in small molecule drug design while establishing advanced small molecule NMR. After that she completed a postdoctoral fellowship with H.M. Al-Hashimi at University of Michigan, Ann Arbor, studying RNA dynamics and the structure of RNA excited states, resulting in two Nature publications. In 2014, she started her own lab at the Karolinska Institute, Stockholm. She has received a number of prices, e.g. the Ampere price of the NMR society and the Wallenberg Academy Fellow. Her group’s research focuses on the study of RNA dynamics of disease related systems, such as ribosomes, microRNAs (Nature 2020) or RNA viruses. The group works both on method development for NMR and RNA biophysics, as well as identifying regulatory mechanism in RNA based on structural changes, so called excited states.
Structure-Based Design of a Phosphotyrosine-Masked, Cell Penetrant Small Molecule Covalently Targeting the E3 Ligase SOCS2 (IL08)
Dr Sarath RAMACHANDRAN
UNIVERSITY OF DUNDEE, Scotland, United Kingdom Read more
Dr Sarath RAMACHANDRAN
Sarat recently joined as a senior drug discovery scientist (structural biology/biophysics) in CeTPD-Boehringer-Ingelheim (ACBI) collaboration team which is working on tackling challenging cancer targets using targeted protein degradation. Prior to joining the ACBI team, he was leading the EUbOPEN collaboration from Alessio’s lab and was involved with developing chemical probes targeting novel E3 ligases and expanding the current arsenal of E3 ligase recruiting PROTAC handles. He joined Alessio’s lab in 2017 after completion of his Ph.D. under the supervision of Prof. Sivaraman Jayaraman at the National University of Singapore, where he worked on understanding the allosteric inhibition mechanism of a key cancer target - glutaminase. Sarat did his Master’s in Biotechnology from Indian Institute of Technology-Guwahati, and bachelor's in Biotechnology from Visveswaraiah Technological University, Karnataka (India).
In-cell NMR to study RNA Structure and Folding (IL04)
Prof. Harald SCHWALBE
J.W. GOETHE UNIVERSITY FRANKFURT, Frankfurt am Main, Germany Read more
Prof. Harald SCHWALBE
H. Schwalbe's graduate and post-doctoral training with Prof. C. Griesinger at Frankfurt University was in the development of NMR methods for the study of conformational dynamics in RNA and proteins. During his post-doctoral fellowship with Prof. C. Dobson at Oxford from 1993-1995, he analyzed the unfolded state of proteins and developed a model for the random coil state of a protein. During his tenure at MIT from 1999-2001, he developed methods to trigger protein folding and photocycles of membrane proteins by light irradiation in situ.
Starting with his appointment as Full professor for organic chemistry, we developed both chemical and biochemical methodology for the preparation of isotope-labeled RNAs in high purity and quantity. We investigated structure and light-triggered RNA folding by ligand release from photolabile precursors molecules of numerous RNA riboswitches. Recently, we could also extend such studies to in-cell NMR spectroscopy to show that bacterial riboswitches retain their function also within eukaryotic cells. The application of time-resolved NMR triggered by laser irradiation was applied to protein folding, RNA and DNA folding, in particular G-quadruplex and i-motif structures as well as for protein with light-sensitive cofactors. Affiliated to the Institute of Organic Chemistry, we also developed an active program in the development of inhibitors for protein kinases in collaboration with Sanofi and protein phosphatases. Our work involved the first NMR resonance assignment of the catalytic domain of a protein kinase, the patented developed of protein kinase and phosphatase inhibitors. As current highlight, we developed kinase inhibitors for EphA2 tyrosine receptor kinases in collaboration with the Tosato group at NIH.
In March 2020, we initiated coordinated NMR research to study the proteome and genome of SARS-CoV-2. We succeeded in making all conserved RNA regulatory elements of virus available, assigned the NMR spectra and conducted NMR-based fragment screening of all these elements. We further expressed 85% of the proteins with the SARS-CoV-2 proteome, reported on near to complete chemical shift assignment for 11 proteins, and conducted NMR-based screens against all these proteins.
H. Schwalbe has authored >350 peer-reviewed publications reporting on orginal contributions, 72 reviews, 5 patents.
Measuring Ligand Binding in Cells Using CETSA® (IL03)
Joe works within Discovery Sciences at AstraZeneca where he is responsible for building cell-based assays to support early drug discovery projects, primarily against Oncology targets. Increasingly, such drug discovery projects seek to use target-proximal cell assays that provide clear and unambiguous data about what compounds are doing in cells in order to accelerate the early stages of lead generation. This has driven uptake in technologies to directly assess binding to a target of interest in a cellular setting. We will share learnings from the internalisation and application of high-throughput CETSA® across AstraZeneca’s Oncology portfolio, developing methods to apply CETSA® broadly across drug discovery and informing how best to utilise the technology in drug discovery projects. We will present multiple case studies demonstrating how measuring ligand binding in cells by CETSA® can advance drug discovery projects.
Fluorescent Nucleobase Analogues - minimally Perturbing Labels in Nucleic Acid Biophysics and Bioimaging as well as Drug Discovery (IL01)
Prof. Marcus WILHELMSSON
CHALMERS UNIVERSITY OF TECHNOLOGY, Gothenburg, Sweden Read more
Prof. Marcus WILHELMSSON
Marcus Wilhelmsson (1974) was awarded his Ph.D. (2003) from Chalmers University of Technology where he is now a Full Professor (2020) of Physical Chemistry and head of the division of Chemistry and Biochemistry.
Wilhelmsson’s research concerns development and characterization of bio-mimicking fluorophores for nucleic acids and methodology for their utilization. He is a key player in the field of fluorescent nucleobase analogues and has pioneered their use in FRET applications – a methodology termed interbase FRET. He has used this to study structure and dynamics of nucleic acids and their interaction with biomolecules and drugs. Recently, he took the field of fluorescent nucleobase analogues to a new level when he demonstrated their in-vitro transcription into mRNA, subsequent in-cell translation to the corresponding protein, and use in live-cell imaging. This has applications in studies of mRNA-based drugs and vaccines. He also has activities in DNA nanotechnology and optical tweezers investigations of nucleic acids.
Together with Yitzhak Tor (UCSD), Wilhelmsson has edited a book regarding fluorescent biomolecules and founded the conference series Fluorescent Biomolecules and their Building Blocks (FB3). For his accomplishments he has been awarded the John Ericsson Medal, the Stenbäcks Stiftelse Award (Finland), and the Chalmers’ Areas of Advance Award.
Binding of Small Molecules to Oligonucleotides in Drug Discovery (OC02)
Nina Grossmann studied biochemistry in Halle/Saale, Germany. After this, she worked as research scientist at the University of Michigan, Ann Arbor, USA where she studied protein folding. In 2006 she started to work on her PhD in biochemistry at Goethe-University, Frankfurt, Germany. Her research focus was membrane proteins and the mode of action of ABC transporters. In 2010, Nina started as a postdoctoral fellow in the Institute of Biochemistry at the Medical Center in Frankfurt to study protein functions in the tumor microenvironment. In 2006 she joined Merck, Darmstadt as a Scientist and lab head. Her lab is currently working on the establishment of biochemical assays for high-throughput screening and mode of action studies by biophysical methods.
The Use of Dual Targeted Bicycles® to Induce Localised CD137 Agonism (OC04)
Dr Peter BROWN
BICYCLE THERAPEUTICS, Cambridge, United Kingdom Read more
Dr Peter BROWN
Peter got his Degree and PhD at the University of Edinburgh, after which he had a postdoc in Colorado.
Once he returned to the UK he transitioned to more industry like roles as a biophysicist for the Drug Discovery Unit (DDU) at CRUK Beatson Institute in Glasgow where he worked on hard to drug targets such as KRas. From hard to drug targets Peter moved to the Membrane protein field working on GPCRs at SoseiHeptares primarily supporting SPR. Recently, Peter started a role as the Biophysics Team leader at Bicycle Therapeutics working across the portfolio to deliver early screening validation biophysics support to generate a new class of therapeutics.
Biophysical Methods Enabling Structure-Based Drug Discovery on Membrane Protein Targets (OC05)
Michael Hennig studied Physics and Biochemistry, received the Ph.D. in structural biology at EMBL Hamburg, and the Charité, Humboldt University Berlin, Germany.
It followed two years postdoc work at the Biozentrum, University of Basel, Switzerland. He is author of more than 100 scientific peer reviewed paper and, since 2011, guest professor in structural biology at the University of Basel.
Michael worked 20 years at Roche, Basel, Switzerland in various positions in drug discovery pioneering structure-based drug discovery. As Global Head and Principle Leader of discovery technologies he assumed global responsibility for structure-based drug discovery, protein science, assay development and HTS, Roche corporate compound library, stem cell platform and analytical physical methods.
In 2015, he co-founded leadXpro, a Biotech company dedicated to enable structure-based drug discovery for membrane protein targets (GPCR’s, Ion-channels, Transporter) and utilizing most advanced biophysical and structure determination technologies such as the X-ray free electron laser and cryo-electron microscopy.
The Biophysics in the Discovery of Potent cGAS Inhibitors (OC08)
Dr Manuel HILBERT
F. HOFFMANN-LA ROCHE LTD, Basel, Switzerland Read more
Dr Manuel HILBERT
Molecular Interaction Scientist at pRED Basel, F. Hoffmann-La Roche;
Since 2014 focus on “Doing now what patients need next”
PostDoc in Biophysical Interactions and Structural Biology, Paul Scherrer Institute Villigen (Prof. Michel Steinmetz) 2010-2014 focus on molecular understanding of centriole duplication
PhD, Department of Biophysical Chemistry, Biozentrum Basel (Prof. Klostermeier) 2010 focus on conformational dynamics of RNA helicases and Topoisomerases with smFRET
Structure-based Design of RNA-Binding Small Molecules and their Binding Characterization via MST, (kin)ITC and SwitchSENSE Assays (OC01)
Dr Christian KERSTEN
JOHANNES GUTENBERG UNIVERSITY, Mainz, Germany Read more
Dr Christian KERSTEN
Christian is a pharmacist by training who obtained his PhD in medicinal/pharmaceutical chemistry at the Johannes Gutenberg University, Mainz and the University of Bergen, Norway under the supervision of Prof. Dr. Ruth Brenk for the elucidation of selectivity determining features in proteins with conserved binding sites. Since 2017, he is assistant professor at the University of Mainz in the group of Prof. Tanja Schirmeister. Besides the structure-based inhibitor design for targets of pharmaceutical interest, especially in the field of neglected tropical diseases, his research focusses on the interplay between molecular recognition and ligand binding thermodynamics and kinetics making use of computational and biophysical methods. In the novel field of small molecule RNA-ligand development, his work aims to improve the understanding of molecular interactions and the application of rational structure-based design methods for bacterial riboswitches and viral RNA targets.
Discovery and Characterization of Active Small Molecule Ligands Targeting the Function of Ubiquitin Specific Protease USP7 by a Catalytic Site Independent Mechanism (OC07)
Prof. Till MAURER
IDEAYA BIOSCIENCES, South San Francisco, United States Read more
Prof. Till MAURER
Current title and positions: Senior Principal Research Scientist in Biophysics, Lead Discovery, Ideaya Bioscience, South San Francisco, Adjunct Professor, Fakultät für Biologie und Vorklinische Medizin Lehrstuhl Biophysik II, Regensburg University
Research field: Using the Biophysics toolchest in observing and understanding molecular interaction, and its application in drug discovery
Past Positions: 2019-2022: Director and Principal Scientist, MSD, Rahway and West Point
2009-2018: Senior Scientist, Genentech, South San Francisco
2008-2009: Principal Scientist, Merck KGaA, Darmstadt
2001-2008: Senior Scientist Boehringer Ingelheim, Biberach/Ingelheim
1995-2001: Assistant professor, Regensburg University
Observing Reversible Engagement of KRAS Hotspot Mutants at the Switch-2 Pocket in Cells (OC03)
Mr Matthew ROBERS
PROMEGA, Madison, United States
Applying Biophysical Interaction Methods to Characterize Binary and Ternary Complex Formation (OC06)
Daniel Schwarz earned his PhD from Goethe University Frankfurt/Main, Germany in Biophysical Chemistry for his work on the structural and functional characterization of membrane embedded proteins. In 2010 Daniel joined Merck Healthcare KGaA as a bench scientist in the department of Molecular Interactions and Biophysics. He currently holds a Principal Scientist position within the Discovery & Development Technology unit and leads a team in the department of Discovery Pharmacology.
His actual Drug Discovery research concentrates on the characterization of molecular interactions by various biophysical methods in a cell free environment. It covers a broad range of activities: fragment screening, analysis of binding kinetics of small molecules as well as of biologics/ADCs and species/isoform selectivity of drug-target interactions. Since a few years ternary complex formation assays for the analysis of small molecules, inhibiting DNA or RNA modifying enzymes or triggering protein degradation, as well as various assay formats providing insights into the molecular mode of drug/target binding complement Daniels Discovery research activities.
Towards Regulation of MDM2 via Stabilisation of a Complex Protein-Protein Interaction (OC09)
Mr Jake WARD
UNIVERSITY OF LEICESTER, Leicester, United Kingdom Read more
Mr Jake WARD
Jake earned his bachelor’s degree in Medical Biochemistry from the University of Birmingham, UK in 2017. During his degree he conducted research with Professor Mark Wheatley, where he investigated the interaction between oxytocin and the human oxytocin receptor. Following completion of his degree he worked in preclinical toxicology for 2 years. In this role he oversaw the running of both general and reproductive toxicology studies across a vast range of therapeutic areas. Jake started his PhD at the University of Leicester in 2019 under the supervision of Dr Richard Doveston and Professor Salvador Macip. His PhD research is focused on using biophysical and structural biology techniques to characterise protein-protein interactions and assess the feasibility of drugging these interactions as a therapeutic modality.