Category:

Gribbon, Philip

May 25th, 2021 by

Curriculum Vitae: Dr Philip Gribbon

Date of Birth: 13/07/1968

Nationality : British/Irish

Contact: Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP Schnackenburgallee 114, D-22525 Hamburg

Phone:   +49 40 303764 271

E-mail:    philip.gribbon@itmp.fraunhofer.de

Website: http://www.itmp.fraunhofer.de

Position: Head of Discovery Research, Fraunhofer ITMP


Employment

2021 –              Head, Discovery Research, Fraunhofer ITMP, Hamburg, DE   

2014 – 2020     Co-Head of Department, Fraunhofer Institute of Molecular Biology and Applied Ecology (IME), ScreeningPort, Hamburg, DE

2008 – 2014     Chief Scientific and Operating Officer, European ScreeningPort GmbH. Hamburg, DE

2005 – 2007     Manager, GlaxoSmithKline Ltd Stevenage, UK.

2000 – 2005     Senior Principle Scientist, Pfizer Ltd, Sandwich, UK.

1995 – 1999     Post-Doctoral Research Associate, Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, UK.

Education

1991 – 1995     PhD in Biophysics, Imperial College, London.

1990 – 1991     MSc in Applied Optics, Imperial College, London.

1987- 1990      BSc (Hons) in Physics, Imperial College, London.

Other activities

2020-               Conference Chair SLAS Europe 2021, Vienna

2020-               Member European Education Committee, Society for Laboratory Automation Sciences

2019-               Chair of the Advocacy Committee, Society for Laboratory Automation Sciences

2019                Conference Chair, European Chemical Biology Symposium, Madrid

2018-2019       Chair of the Europe Committee of the Society for Laboratory Automation Sciences

2018-2020       Scientific advisor to Kaertor Foundation (Galicia, Spain)

2018-2020       Fellow of the Society of Laboratory Automation Sciences

2017                Conference Chair, European Chemical Biology Symposium, Budapest

2015-2018       Member ESFRI Life Science Infrastructure Strategy Board

2015                Conference Chair, European Chemical Biology Symposium, Berlin

2014-2018       Coordinator of EU-OPENSCREEN, the European Research Infrastructure for Chemical Biology and Screening

Selected Publications

  1. Ellinger B, Bojkova D, …Gribbon P and Ciesek S. A SARS-CoV-2 cytopathicity dataset generated by high-content screening of a large drug repurposing collection, Scientific Data 8, Article number: 70 (2021), 2021
  2. Kuzikov, M….Gribbon P and Zaliani, A. Identification of Inhibitors of SARS-CoV-2 3CL-Pro Enzymatic Activity Using a Small Molecule in Vitro Repurposing Screen, ACS Pharmacology and Translational Science 2021 (in the press) https://doi.org/10.1021/acsptsci.0c00216
  3. Gossen J, …Gribbon P,…Rossetti G. A Blueprint for High Affinity SARS-CoV-2 Mpro Inhibitors from Activity-Based Compound Library Screening Guided by Analysis of Protein Dynamics. ACS Pharmacology and Translational Science 2021 (in the press) https://doi.org/10.1021/acsptsci.0c00215
  4. Günther A…Gribbon P…and Meents A. Massive X-ray screening reveals two allosteric drug binding sites of SARS-CoV-2 main protease. (In final review) preprint here: https://doi.org/10.1101/2020.11.12.378422
  5. Witt, G… Gribbon P and Pless O. An automated and high-throughput-screening compatible pluripotent stem cell-based test platform for developmental and reproductive toxicity assessment of small molecule compounds. Cell Biol Toxicol 2020. https://doi.org/10.1007/s10565-020-09538-0.
  6. Ehrnhoefer DE, Skotte NH…Gribbon P, et al. Activation of Caspase-6 Is Promoted by a Mutant Huntingtin Fragment and Blocked by an Allosteric Inhibitor Compound. Cell chemical biology, 26 (9), 1295-1305. e6 2019
  7. Brennecke P,…Gribbon P. EU-OPENSCREEN: A novel collaborative approach to facilitate chemical biology. SLAS Discovery: Advancing Life Sciences R&d 24 (3), 398-413, 2019
  8. Sassetti E,…Gribbon P, et al. Identification and Characterization of Approved Drugs and Drug-Like Compounds as Covalent Escherichia coli ClpP Inhibitors. International journal of molecular sciences 20 (11), 2686,
  9. Moreno-Cinos C, … Gribbon P, et al. α-Amino Diphenyl Phosphonates as Novel Inhibitors of Escherichia coli ClpP Protease. Journal of medicinal chemistry 62 (2), 774-797, 2018.
  10. de Witte WEA,… Gribbon P… et al. In vitro and in silico analysis of the effects of D2 receptor antagonist target binding kinetics on the cellular response to fluctuating dopamine concentrations. British journal of pharmacology 175 (21), 4121-4136, 2018
  11. Gilardi A,…Gribbon P,… et al. Biophysical characterization of E. coli TolC interaction with the known blocker hexaamminecobalt. Biochimica et Biophysica Acta (BBA)-General Subjects, 1861 (11), 2702-2709, 2018.
  12. Korostylev A, Mahaddalkar PU, Keminer O, Hadian K, Schorpp K, Gribbon P and Lickert, H.  A high-content small molecule screen identifies novel inducers of definitive endoderm Molecular Metabolism 6(7), 640–650, 2017.
  13. De Sousa PA, … Gribbon P.. et al. Rapid establishment of the European Bank for induced Pluripotent Stem Cells (EBiSC)-the Hot Start experience. Stem cell research 20, 105-114,
  14. Borsari C….Gribbon P…et al. Profiling of Flavonol Derivatives for the Development of Antitrypanosomatidic Drugs. Journal of medicinal chemistry 59 (16), 7598-7616,
  15. Rees S, Gribbon P, Birmingham K, Janzen WP and Pairaudeau G. Towards a hit for every target. Nature Reviews Drug Discovery, 15;1–2

Title

” Compound repurposing by target based and phenotypic approaches to identify in-vitro inhibitors of SARS-CoV2 viral entry and replication ”

Abstract:

Compound repurposing is an important strategy to aid the identification of effective treatment options against SARS-CoV-2 infection and COVID-19 disease. The presentation will cover the results of several repurposing programs based on phenotypic and target based screens using a large scale library of bioactive compounds. Target studies will focus on SARS-CoV-2 main protease (3CL-Pro), also termed M-Pro, which is an attractive drug target as it plays a central role in viral replication by processing the viral polyproteins pp1a and pp1ab at multiple distinct cleavage sites. We have confirmed previously reported inhibitors of 3CL-Pro and have identified 62 additional compounds with IC50 values below 1 μM and profiled their selectivity toward chymotrypsin and 3CL-Pro from the Middle East respiratory syndrome virus (see  https://doi.org/10.1021/acsptsci.0c00216 and https://doi.org/10.1021/acsptsci.0c00215 ). In phenotypic studies, compounds were screened by microscopy for their ability to inhibit SARS-CoV-2 cytopathicity in the human epithelial colorectal adenocarcinoma cell line, Caco-2 (see https://doi.org/10.1038/s41597-021-00848-4). These studies have been complemented by extensive structural investigations to reveal the binding characteristics of the compounds (see https://www.biorxiv.org/content/10.1101/2020.11.12.378422v1).

Otzen, Daniel

March 12th, 2021 by

Daniel Otzen is Professor of Nanobiotechnology at the Interdisciplinary Nanoscience Center (iNANO) at Aarhus University. Daniel Otzen has an MSc degree (1992) in Molecular Biology from Aarhus University and a PhD (1995) in protein biophysics from the lab of Sir Alan Fersht at Cambridge University jointly with Aarhus University. He has worked with protein stability, folding and misfolding his whole career. After 2 years as research chemist (1995-1997) at Novozymes A/S (which stimulated his interest in the impact of surfactants on protein stability and structure), he returned to academia, first as a postdoc at University of Lund (1997-2000) with Mikael Oliveberg and subsequently as Associate Professor and Professor (2000-2007) at the Department of Life and Environmental Sciences at Aalborg University. He joined iNANO as Professor in 2007. His group combines different spectroscopic, calorimetric and structural techniques (scattering and electron microscopy) to address the mechanisms and thermodynamics of protein aggregation and self assembly in health and disease, folding in membranes and micelles and – recently – activity and stability of cold-active enzymes. He has authored > 350 peer-reviewed articles. He is married with two children and uses his spare time to walk the dog and keep the weeds at bay in the garden.


Topic:

Enlisting microfluidics to screen for inhibitors of toxic protein aggregates in Parkinson’s Disease and other disruptors of protein-protein interactions.

Abstract:

Soluble oligomers of the protein alpha-synuclein are believed to be a major cytotoxic agent in the development of Parkinson’s Disease, yet their very dynamic structure makes them difficult drug targets. I will describe our efforts to develop compounds targeting these oligomers by screening for the ability to prevent oligomer interactions with other biological species such as membranes and antibodies. Our approach is to use flow-induced dispersion analysis (FIDA) which allows us to monitor apparent oligomer size, a parameter which changes if the oligomer complexes with other large components. In parallel I will also describe our use of FIDA to identify small molecules to block binding of the SARS-CoV-2 spike protein to the human receptor ACE2.

Ventura, Salvador

February 22nd, 2021 by

Salvador Ventura is Full Prof. at the Dep. of Biochemistry and Molecular Biology and leader of the Protein Folding and Conformational Diseases group at the Institute of Biotechnology and Biomedicine (IBB), Autonomous University of Barcelona (UAB). He has been director of the IBB in 2017-20. Dr. Ventura has authored more than 240 peer-reviewed research and review papers, apart from several book chapters and 13 patents. He got his Ph. D. in Biology at the UAB in 1998 and worked as postdoctoral fellow (1999-2002) at EMBL-Heidelberg. He has been researcher at Harvard Medical School (USA) and Karolinska Institutet (Sweden) among other centres. He rejoined UAB as a Ramon y Cajal researcher in 2003. Dr. Ventura received the UAB 2008 Excellence Research Award, the Bruker Prize “Manuel Rico” 2020 from the Spanish Biophysical Society and 2009, 2015 and 2020 ICREA-Academia Awards in Life Sciences and Medicine.


Abstract:

Finding new drugs for conformational diseases

Topic:

Conformational diseases are pathologies with a great social, economic and personal impact on our society. Some are well-known because they affect a large number of people, like Parkinson’s disease, while others are rare disorders, such as familiar amyloidosis. All these diseases remain incurable. They exhibit very different symptoms and each of these disorders is associated with a different protein. However, the problem that these proteins experiment is always the same: at a given time they become insoluble and toxic and they impact the normal physiology of the tissue or organ in which they reside, independently if this is the heart or the brain. In this presentation I will explain the efforts of our research group to find new drugs that can slow down the progress of these devastating diseases.

Tang, Dora

February 8th, 2021 by

Date of Birth:     31 December 1982

Institution:          Max Planck Institute of Molecular Cell Biology, Pfotenhauerstrasse. 108, 01307

Position:              Independent Research Group Leader

Email:                    tang@mpi-cbg.de

 

Education

2007-2010                          PhD studies in Membrane Biophysics, Imperial College London, UK

Supervisors Profs. John Seddon and Richard Templer

2002-2006                          MSc in Chemistry, Imperial College London

 

Professional Career

Since 2016                          Independent Research Group leader, MPI-CBG, MaxSynBio, Dresden

2014-2016                          Post-doc in Synthetic Biology, with Prof. Stephen Mann and Dr. Ross Anderson,

University of Bristol, U.K.

2011-2014                           Post-doc in Origin of Life studies, with Prof. Stephen Mann, University of Bristol, U.K.

2010-2011                         Knowledge Transfer Secondee, Diamond Light Source, Oxfordshire, UK.

 

Fellowships and Awards

2019-present                     Fellow of Elisabeth-Schiemann Kolleg, Max Planck Society

2018                                       Fellow, Centre for Advanced studies, Ludwig Maximillian University, Munich

Since 2016                           Fellow, B Cube, Center for Molecular Bioengineering, TU Dresden

2010-2011                            EPSRC Knowledge Transfer Secondment

2006                                       Degussa Prize for Physical Chemistry


Topic:

Coacervates as protocellular models?

Abstract:

In the 1920’s Oparin hypothesized that membrane free compartments formed by coacervation would have provided a viable route to compartmentalize prebiotic reactions as a precursor to the modern cell. Studies which support this hypothesis are limited in that the precise chemical composition and conditions on prebiotic earth remain a mystery. Despite this, using bottom-up approaches allows us to generate physically relevant protocell models in the lab. This provides a means to unravel the effect of compartmentalization by coacervation can have provided a selection pressure for facilitating the transition from a chemical world to a biological world.

Here, I will present strategies for the design and synthesis of protocell models based on liquid-liquid phase separation of oppositely charged components (coacervates) and describe how these compartments can provide alternative environments compared to buffer solution to tune reaction kinetics.

Powner, Matthew

February 8th, 2021 by

Matthew Powner obtained a master’s degree (2005) and PhD (2009) in chemistry at the University of Manchester. Then completed a short EPSRC Doctoral Prize postdoctoral fellowship with John Sutherland, and was awarded a Harvard Fellowship to work with Jack Szostak at Massachusetts General Hospital. He joined UCL (2011) as a lecturer in the chemistry department, where he is currently Professor of Organic Chemistry. He has been awarded various prizes and fellowships in recognition of his research, including the Stanley Miller Award (2011), the Roscoe Medal (2012), Origins of Life Challenge (2012; joint 1st prize with John Sutherland), an EPSRC Early Career Fellowship (2013), Thieme Chemistry Journal Award (2015), the RSC Harrison-Meldola Memorial Prize (2019) and Blavatnik Awards UK Finalist (2021).


Abstract:

On the unified chemical origins of peptides and nucleic acids

Topic:

Living organisms are highly complex chemical systems that exploit a small constellation of universally conserved metabolites. The chemical unity of these metabolites provides compelling evidence that a simple set of predisposed reactions predicated the appearance of life on Earth. Conversely, traditional prebiotic chemistry has produced highly complex mixtures that bear little resemblance to the core metabolites of life. The complexity of prebiotic chemistry until recently had suggested that elucidating life’s origins was an insurmountable task, but prebiotic systems chemistry is now providing unprecedented scope to explore the origins of life and an exciting new perspective on a 4 billion-year-old problem. At the heart of this new systems approach is an understanding that individual classes of metabolites cannot be considered in isolation if the chemical origin of life on Earth is to be successfully elucidated. In this talk several recent advances suggesting the proteinogenic peptides and canonical nucleotides are predisposed chemical structures will be presented.

Codee, Jeroen

February 8th, 2021 by

Jeroen Codée (1975) obtained his PhD degree form Leiden University (2004) under the guidance of Prof. Jacques van Boom and Prof. Stan van Boeckel, working on the synthesis of heparin oligosaccharides and the development of new methods for glycosylations of thioglycosides. After a post-doctoral say in Zurich as an NWO-talent fellow, at the ETH with Prof. Peter Seeberger, where Jeroen was trained in automated and continuous flow synthesis techniques, he returned to Leiden University as a NWO Veni-fellow to set up a carbohydrate synthesis group within the Leiden University Bio-Organic Synthesis (BIOSYN) department. His research focuses on all aspects of oligosaccharide synthesis and the application of synthetic carbohydrates in chemical glycobiology and glycoimmunology. In particular he is interested in unravelling the mechanism of glycosylation reactions and construction of complex bacterial oligosaccharides, featuring unusual substitution patterns and challenging glycosidic linkages. He received an ERC Consolidator grant (2016), a NWO VICI grant (2018) and he was awarded the Carbohydrate Research Award for Creativity in Carbohydrate Chemistry (2017).


Abstract:

Of sugars and phosphates: synthesis and application of well-defined bacterial oligosaccharide structures

Topic:

We are in a constant battle with bacteria infecting us. Bacteria protect themselves with a cell wall, decorated with various -often heterogeneous- glycan structures. To study the role of these glycans in the interaction with the host immune system, well-defined, homogeneous structures are required. Since these cannot be obtained in sufficient quantity and quality from bacterial sources, we have developed various routes of synthesis to generate bacterial glycans. Here we will describe how automated synthesis techniques can be used to generate bacterial phosphate-based glycans. Libraries of synthetic teichoic acids have been used in vaccination studies against the multi-drug resistant hospital bugs E. faecalis and S. aureus and to map antibody binding interactions at the molecular level. Stabilized analogues of N. meningitidis have been developed to generate shelf stable vaccines against this bacterium: the first carbohydrate vaccine using a glycomimetic antigen.

Rovira, Carme

February 8th, 2021 by

Carme Rovira is an ICREA Research Professor at the Department of Chemistry of the University of Barcelona (UB). She obtained her PhD degree in Chemistry from the UB in 1995 and was Marie-Curie postdoctoral fellow at the Max-Planck-Institute für Festkörperforschung (Stuttgart, Germany, 1996-1998), working with M. Parrinello. After another postdoc at UB, she obtained a Ramón y Cajal position (2002-2006) and started her research group. Carme was appointed ICREA Research Professor in 2007 and has been  visiting Professor at the University of York (UK, 2019). She has received research awards from the Catalan Government (2003), the Barcelona City Council (2016) and the European Carbohydrate Organisation (2019). She received an ERC SyG grant in 2020. She is the author of about 170 publications in peer-reviewed journals as well as book chapters, mainly in the fields of physical chemistry and computational biology. The research at Carme’s lab is focused on the simulation of ligand-protein interactions and enzyme catalytic processes that can guide enzyme engineering and drug design. Her current research is focused on carbohydrate-active enzymes (glycosidases, glycosyltransferases and lytic polysaccharide monooxygenases).


Topic:

Using computers to understand how carbohydrates are processed in nature

Abstract:

Carbohydrate-active enzymes (CAZymes), such as glycoside hydrolases and glycosyltransferases, constitute the main machinery for the degradation and synthesis of carbohydrates in nature. They have a myriad of industrial and biotechnological applications, ranging from biofuel production to drug design. In recent years, new CAZyme structures have been solved that pose mechanistic questions on how their carbohydrate substrates are processed, such as the identity of the catalytic residues, the role of enzyme conformational transitions and the distortion of the substrate at the transition state of the chemical reaction.  Using state-of-art simulation techniques such as ab initio quantum mechanics/molecular mechanics (QM/MM) and metadynamics [1-3] we have contributed to answer these questions,  providing an atomistic view of enzyme action that can guide inhibitor design. In this talk I will describe some of the CAZyme mechanisms that we have recently investigated, in a collaborative work with experimental groups [4-6].

Sattin, Sara

February 8th, 2021 by

Sara Sattin graduated in Industrial Chemistry and Management and then obtained my PhD in Chemical Sciences in 2009 at the University of Milan (Università degli Studi di Milano) working on the synthesis of mono- and multivalent glycomimetc inhibitors of DC-SIGN mediated infections. After a 2-years postdoc at the ICIQ-Tarragona (ES) working on supramolecular chemistry (UOF-based cages) I moved to the University of Oxford (UK) to work in the fascinating field of chemical biology. In late 2013, I moved back to Milan where I worked as a senior postdoc on the chemical allosteric modulation of the hub protein Hsp90. In 2017, I became Assistant Professor and I have been awarded an ERC Starting Grant towards the eradication of chronic infections. Since 2018, I am Associate professor in Organic Chemistry.


Abstract:

Interfering with bacterial survival strategies

Topic:

Persistence is a bacterial bet hedging strategy that allows for temporary tolerance to antibiotic treatment. This phenotypic switch paves the way to the chronicity of certain infections and to the insurgence of genetic resistance. Here we present our work on targeting bacterial persisters via inhibition of the upstream of the stringent response, one of the working hypothesis for their formation. Our multidisciplinary approach comprises in silico studies on Rel proteins, synthesis of compounds designed ad hoc and evaluation of their biological activity.

Hackenberger, Christian

February 8th, 2021 by

Christian Hackenberger studied chemistry in Freiburg, Madison and Aachen. After a postdoc at MIT, he started his group at FU Berlin in 2005 as an Emmy Noether fellow. In 2012, he became Leibniz-Humboldt Professor for Chemical Biology at the Leibniz-Research Institute for Molecular Pharmacology and the HU Berlin. His group develops chemical strategies to functionalize proteins and antibodies to generate protein-based pharmaceuticals against cancer, Alzheimer and viral infections. He is a co-founder of Tubulis, which engineers better tolerable cancer drugs using technologies from his lab.


Abstract:

The power of chemoselectivity: Functional protein-conjugates for intra- and extracellular targeting

Topic:

In this presentation, l will focus on the chemical modification of functional proteins for for pharmaceutical and medicinal applications.1 In my laboratory, we use a combined approach of recently developed chemoselective reactions and enzymatic ligations, for instance the so-called P5-2 or Tub-tag3-labeling, for bioconjugation.

By generating stable antibody-drug conjugates (ADCs),2b structurally defined multivalent scaffolds4 or cell-permeable antibodies via conjugating cyclic cell-penetrating peptides,5 we provide new modalities for most challenging pharmaceutical targets, including next generation cancer therapeutics or novel inhibitors against viral infections.

 

 

Wade, Rebecca

February 8th, 2021 by

Rebecca Wade leads the Molecular and Cellular Modeling group at Heidelberg Institute for Theoretical Studies (HITS) and is Professor of Computational Structural Biology at the Center for Molecular Biology at Heidelberg University (ZMBH).  Rebecca Wade’s research is focused on the development and application of computer-aided methods to model and simulate biomolecular interactions. Her research group has developed novel protein structure-based methods for drug discovery and protein engineering, most recently for studying drug binding kinetics, as well as multiresolution computational approaches to investigate macromolecular association and the effects of macromolecular crowding.  URL: mcm.h-its.org.


Abstract:

Combining molecular simulation and machine learning approaches for structure-based drug design

Topic:

Structure-based drug design approaches increasingly require the handling of very large amounts of data, such as large compound libraries for screening or many protein conformations generated by molecular dynamics simulations. There is also the need to integrate diverse types of experimental and computational data into the design process. I will describe examples of how we are addressing these issues by combining molecular simulation and machine learning approaches [1-5]. We focus in particular on the challenges and opportunities for drug design provided by protein binding pocket dynamics. I will present the development and recent applications of a machine learning approach to identify pocket conformations with high druggability in TRAPP, a toolbox of computational approaches to identify TRAnsient Pockets in Proteins for ligand design (https://trapp.h-its.org/).  Protein binding site flexibility is one of the factors that can affect drug-target binding kinetics. Growing evidence that the efficacy of a drug can be correlated to target binding kinetics has led to the development of many new methods aimed at computing rate constants for receptor-ligand binding processes, see: kbbox.h-its.org. I will introduce the t-random acceleration molecular dynamics simulation (tRAMD) method to compute relative residence times and discuss how interaction fingerprint (MD-IFP) and machine learning analysis of tRAMD trajectories can be used to decipher the determinants of drug-target residence times.