- Circadian clocks and metabolism
- Drug discovery, delivery and kinetics
- Signaling and interactions
- Real-time monitoring of reactions and biochemical events
Chemistry and Time
Beilstein Bozen Symposium 2014
19 – 23 Mai 2014
Yachthotel Chiemsee, Prien (Chiemsee), Germany
Organized by Martin G. Hicks and Carsten Kettner, Beilstein-Institut
Aspects covered by this conference
- Electron transfer systems
- Systems and synthetic biology
- Developmental biology and evolution
Introduction
The Beilstein Symposia address contemporary issues in chemistry and neighboring sciences by emphasizing interdisciplinarity. Scientists from a wide range of areas – often outside chemistry – are invited to present aspects of their work for discussion with the aim not only to advance science, but also to enhance interdisciplinary communication.
Temporal measurements of phenomena have been carried out continuously by natural scientists over the centuries. Time is the dimension used to order events from the past via the present to the future and is not reversible (even though mankind still dreams of time machines that enable travel into the past or future). This irreversibility is determined by thermodynamics, which describes the direction of events by the increase of entropy. For most people, the external "Zeitgeber" that regulate our biological rhythms combined with aging, reproduction, evolution and geology make time very real and directional. Time is relative and asymmetric – or isn't it?
Whether time is real or an illusion is an ancient question that is still waiting to be answered. The ancient Greeks had two words for time; chronos and kairos. Chronos refers to the sequential nature of time and kairos the right moment to make a decision, for example during signaling, synchronization of events, regulation and monitoring.
In chemistry and biology, reactions depend on external factors such as light and temperature. The velocity of a reaction is determined as products formed per time unit, which is expressed by kinetics. The bottleneck of a "time-dependent" reaction is not time but intramolecular (reversible) modifications, diffusion, ligand binding, electron or energy transfer and molecular association and dissociation processes (which all are a function of time). However, the processes are characterized by time-dependent rate coefficients.
In nature there is no mechanical clock that sets up a scale unit for processes that need to follow each other, such as biochemical reactions in plants, animals and microorganisms. There are different mechanisms that arrange the order of chemical reactions depending on the need for their products: biochemical pacemakers as investigated in chronobiology, separation of reactions or charges by space and external pacemakers such as light and temperature. Reactions can be fast or slow, from femtoseconds to thousands of years. Biological time covers events from near instantaneous to generations. Chemistry must take the required sequence of events and the correct timing into account.
This symposium brought together experts from many disciplines to present and discuss their latest research results and give participants different perspectives on chemistry and time. Areas covered include: signaling, photosynthesis, chronobiology, drug development, delivery and resistance, real-time monitoring of reactions and biochemical events and developmental biology.
Summary
by David A. Winkler, CSIRO Manufacturing Flagship, Clayton, Australia
The Beilstein Symposia address contemporary issues in chemistry and neighbouring sciences by emphasizing interdisciplinarity. Scientists from a wide range of areas – often outside chemistry – are invited to present aspects of their work for discussion with the aim, not only of advancing science, but also of enhance interdisciplinary communication.
The Bozen Symposia topics are deliberatively broad to encourage the most lateral interpretations of contemporary themes in chemistry. The Symposium on Chemistry and Time brought together experts from many disciplines to present and discuss their latest research results and give participants different perspectives on chemistry and time. As Einstein has taught us, there is also an intimate relationship between space and time. Space-time is a mathematical model that combines space and time into a single interwoven continuum. It allows us to blend space and time into a single abstract Minkowski universe. Mathematically it is a manifold consisting of "events" which are described by some type of coordinate system. Typically three spatial dimensions (length, width, height), and one temporal dimension (time) are required.
This duality of space and time was a theme woven through many of the presentations, from femtosecond studies of nanoscale materials to billion year studies of the unbounded Universe. This relationship between space and time was taken further by some papers that explored vast chemical spaces using experimental or computational approaches capable of greatly contracting the time required to traverse these spaces.
There was strong representation from traditional areas of chemistry where temporal issues are clearly prominent, such as the dynamic behaviour of biological systems at the molecular scale and spectroscopy at very short timescales. However, chemical aspects of important biological systems were also discussed in detail, opening up new or non-traditional research areas at the exciting interface between chemistry and biology. Chronobiology, sleep cycles, and circadian rhythms were prominent amongst the topics, crossing over into the topics of biological ageing. Newer topics included self-assembly and chemical and biological evolution, particularly the possibility of evolving materials and molecules for specific purposes (fitness), and the use of catalysis to accelerate chemical synthesis of 'green' fuels from water and CO2.
Computational modelling of systems across large physical and temporal scales timescales was also an important part of the discussion, particularly in exploring the chemical kinetics of metabolism, the dynamics of ligand-protein interactions, the evolution of molecules, materials, and organisms, and the behaviour of chemical networks.
The Symposium, as it was designed to do, generated deep discussions within and outside of the formal sessions, finding connections between disciplines that would otherwise be left unexplored. The networks established at the meeting, and the ideas the Symposium stimulated, will undoubtedly endure and grow into the future.
Scientific Program
Disruptions on the Highways of Communication
Dario Alessi, University of Dundee, UK
Life Stages, Ageing, and the Nature of Biological Time
Adam Antebi, Max Planck Institute for Biology of Ageing, Cologne, Germany
Multiprotein Assemblies in Space and Time: Implications for Cell Signalling and Drug Discovery
Tom L. Blundell, University of Cambridge, UK
Sequestration of Plant-Derived Glycosides by Leaf beetles: a Model System for Evolution and Adaptation
Wilhelm Boland, Max Planck Institute for Chemical Ecology, Jena, Germany
Simulating Things Moving at Different Speeds
Timothy Clark, University of Erlangen-Nürnberg, Germany
Engineering Evolution in Chemistry and Biology: Bottom up Meets Top down Synthetic Biology
Leroy Cronin, University of Glasgow, UK
The Logic of Metabolism
Antoine Danchin, AMAbiotics International Ltd, Evry, France
Chemistry and the Garden Pond: the Diverse Metabolism of the Protozoan Alga Euglena gracilis
Rob Field, John Innes Centre, Norwich, UK
Serial Femtosecond Nanocrystallography: Dawn of a New Era in Structural Biology
Petra Fromme, Arizona State University, Tempe, USA
Accurate Modelling of Ligand-target Residence Timie in Protein Kinases
Francesco L. Gervasio, University College London, UK
Dynamic Switchable Biomolecule Nanomaterials as Active Responsive Probes and in vivo Imaging Agents
Nathan C. Gianneschi, University of California, San Diego, USA
Dynamic Nutrient Regulation of Cellular Gene Expression & Physiology by O-GlcNAcylation
Gerald W. Hart, Johns Hopkins University, Baltimore, USA
Understanding of Ligand-protein Interactions in the IMI Kinetics for Drug Discovery (K4DD) Programme
Trevor J. Howe, Janssen-Research and Development, High Wycombe, UK
Understanding the Cellular Uptake of Pharmaceutical Drugs in the Post-genomic Era: a Problem not of Biophysics but of Systems Biology
Douglas B. Kell, University of Manchester, UK
Planned Obsolescence of Canonical Building-blocks Trhough Automated Evolution
Philippe Marlière, Global Energies, Evry, France
Electron Transfer in Proteins: Insights into Principles and Possible Applications
Israel Pecht
The Weizmann Institute of Science, Rehovot, Israel
Metabolic Oscillations in the Circadian Clockwork
Akhilesh B. Reddy
University of Cambridge, UK
Sleep Research in the Real World
Till Roenneberg, Ludwig-Maximilians-Universität München, Germany
Fuels from Solar Energy and Water - from Natural to Artificial Photosynthesis
Stenbjörn Styring, University of Uppsala, Sweden
Modelling of Human Metabolism with the Genome-scale Metabolic Reconstruction Recon 2
Neil Swainston, University of Manchester, UK
Visualizing Functional Motions of Membrane Transporters at High Temporal and Spatial Resolutions
Emad Tajkhorshid, University of Illinois at Urbana-Champaign, USA
Systems and Synthetic Biology of Mammalian Circadian Clocks
Hiroki R. Ueda, Quantitative Biology Center RIKEN, Kobe, Japan
Chemistry Space-Time
David A. Winkler, CSIRO Molecular and Health Technologies, Clayton, Australia
Structural Insights into Clock Protein Chemistry
Eva Wolf, Ludwig-Maximilians-Universität München, Germany