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Reinhart Heinrich | |
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Born | |
Died | 23 October 2006 60) Berlin, Germany | (aged
Alma mater | Dresden University of Technology |
Known for | Metabolism, signal transduction, The Regulation of Cellular Systems |
Awards | Humboldt Prize, Brigitte Reimann Prize, Honorary doctorate from the University of Bordeaux |
Scientific career | |
Fields | Systems biology, biophysics |
Institutions | Charité, Berlin; Humboldt University of Berlin Charité |
Reinhart Heinrich (24 April 1946 – 23 October 2006) was a German biophysicist. [1]
He was professor at the Humboldt University of Berlin, and best known as one of the founders, with Tom Rapoport, of metabolic control theory [2] in parallel with similar ideas developed at about the same time by Henrik Kacser and Jim Burns. [3] His far-reaching theoretical work on metabolism, signal transduction, and other cellular processes has made him one of the most influential forerunners of present-day systems biology. Reinhart's many talents made him appear as a modern Renaissance man. He played the violin, and published an autobiographic novel (Jenseits von Babel [4] ) and several works of lyric poetry for which he received the Brigitte Reimann Prize. Among his services to the scientific community, Reinhart was associate editor of PLoS Computational Biology .
Reinhart Heinrich was born in Dresden and lived at first in the Soviet Union, growing up in Kuybyshev/Куйбышев (called Samara since 1991) where his father Helmut Heinrich — a German mathematician turned aircraft constructor — had been taken after the Second World War to work. [1] Having been educated as a theoretical physicist at Dresden University of Technology in East Germany, Reinhart conducted his postdoctoral research in the early 1970s at the Charité's Institute of Biochemistry in East Berlin. He could not fail to notice the absence of mathematical theory from cell biology as compared with other natural sciences. Enzyme kinetics was a notable exception. However, how enzymes affect the flux through a metabolic pathway was still discussed using the rather vague term rate-limiting step. Working with Tom Rapoport on mathematical models of glycolysis in red blood cells, Reinhart discovered a precise and general definition of rate limitation in metabolic pathways, for which he received in 1974 the Humboldt Prize. [1] He extended his knowledge in this area, working over one year in Pushchino with Evgeni Selkov, [1] who also worked on mathematical modelling of metabolic processes.
The parallel development of metabolic control theory by Henrik Kacser and Jim Burns [3] in Edinburgh shows that the time was ripe for a quantitative understanding of metabolic regulation. Instead of postulating a single rate-limiting step, these theories evaluated the degree of flux control exerted by an individual enzyme in a linear pathway or in a more complex network. The corresponding measure, now called the flux control coefficient by general agreement, [5] turned out to be a truly systemic quantity, depending not only on the kinetic parameters of the enzyme itself but also on those of other enzymes, as well as on the position of the reaction in the network. After a slow start metabolic control theory has become more widely known by biochemists. Control coefficients have been measured for many pathways, confirming the theoretical prediction that flux control is frequently shared by several reactions. This finding has become of practical importance for the genetic engineering of large metabolic networks in biotechnology.
The dual approach — modelling concrete cellular processes and, at the same time, searching for general laws — has been a characteristic of Reinhart's work. The areas he worked in were amazingly diverse, including metabolic control, osmoregulation, cell shapes, signal transduction, vesicular transport, protein translation and transport, as well as the population dynamics of malaria parasites.
Perhaps the questions that interested him the most were those of evolution. [6] To understand the kinetic design of enzymes and enzymatic reaction networks, Reinhart strove to rationalize, in mathematical terms, the selective pressures and physico–chemical constraints that these systems were subjected to. Reinhart's work on this topic is full of original insight and makes specific predictions, some of which have begun to be tested successfully in recent years.
Reinhart was author of more than 160 research articles and, together with Stefan Schuster, the book The Regulation of Cellular Systems, [7] which has become a classic of cell systems biology. In addition to this large body of original work, he was a gifted mentor of young scientists and for more than ten years ran the highly successful interdisciplinary graduate program Dynamics and Evolution of Cellular Processes at Humboldt University, Berlin. In 1996 he received an Honorary degree from the University of Bordeaux.
Metabolism is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the conversion of food to building blocks for proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of metabolic wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments. The word metabolism can also refer to the sum of all chemical reactions that occur in living organisms, including digestion and the transportation of substances into and between different cells, in which case the above described set of reactions within the cells is called intermediary metabolism.
Systems biology is the computational and mathematical analysis and modeling of complex biological systems. It is a biology-based interdisciplinary field of study that focuses on complex interactions within biological systems, using a holistic approach to biological research.
Modelling biological systems is a significant task of systems biology and mathematical biology. Computational systems biology aims to develop and use efficient algorithms, data structures, visualization and communication tools with the goal of computer modelling of biological systems. It involves the use of computer simulations of biological systems, including cellular subsystems, to both analyze and visualize the complex connections of these cellular processes.
Metabolic engineering is the practice of optimizing genetic and regulatory processes within cells to increase the cell's production of a certain substance. These processes are chemical networks that use a series of biochemical reactions and enzymes that allow cells to convert raw materials into molecules necessary for the cell's survival. Metabolic engineering specifically seeks to mathematically model these networks, calculate a yield of useful products, and pin point parts of the network that constrain the production of these products. Genetic engineering techniques can then be used to modify the network in order to relieve these constraints. Once again this modified network can be modeled to calculate the new product yield.
Henrik Kacser FRSE was a Romanian-born biochemist and geneticist who worked in Britain in the 20th century. Kacser's achievements have been recognised by his election to the Royal Society of Edinburgh in 1990, by an honorary doctorate of the University of Bordeaux II in 1993.
Hans Victor Westerhoff is a Dutch biologist and biochemist who is professor of synthetic systems biology at the University of Amsterdam and AstraZeneca professor of systems biology at the University of Manchester. Currently he is a Chair of AstraZeneca and a director of the Manchester Centre for Integrative Systems Biology.
Metabolic network modelling, also known as metabolic network reconstruction or metabolic pathway analysis, allows for an in-depth insight into the molecular mechanisms of a particular organism. In particular, these models correlate the genome with molecular physiology. A reconstruction breaks down metabolic pathways into their respective reactions and enzymes, and analyzes them within the perspective of the entire network. In simplified terms, a reconstruction collects all of the relevant metabolic information of an organism and compiles it in a mathematical model. Validation and analysis of reconstructions can allow identification of key features of metabolism such as growth yield, resource distribution, network robustness, and gene essentiality. This knowledge can then be applied to create novel biotechnology.
Flux balance analysis (FBA) is a mathematical method for simulating metabolism in genome-scale reconstructions of metabolic networks. In comparison to traditional methods of modeling, FBA is less intensive in terms of the input data required for constructing the model. Simulations performed using FBA are computationally inexpensive and can calculate steady-state metabolic fluxes for large models in a few seconds on modern personal computers. The related method of metabolic pathway analysis seeks to find and list all possible pathways between metabolites.
Metabolic control analysis (MCA) is a mathematical framework for describing metabolic, signaling, and genetic pathways. MCA quantifies how variables, such as fluxes and species concentrations, depend on network parameters. In particular, it is able to describe how network-dependent properties, called control coefficients, depend on local properties called elasticities or Elasticity Coefficients.
Flux, or metabolic flux is the rate of turnover of molecules through a metabolic pathway. Flux is regulated by the enzymes involved in a pathway. Within cells, regulation of flux is vital for all metabolic pathways to regulate the pathway's activity under different conditions. Flux is therefore of great interest in metabolic network modelling, where it is analysed via flux balance analysis and metabolic control analysis.
Biochemical systems theory is a mathematical modelling framework for biochemical systems, based on ordinary differential equations (ODE), in which biochemical processes are represented using power-law expansions in the variables of the system.
Igor I. Goryanin is a systems biologist, who holds a Henrik Kacser Chair in Computational Systems Biology at the University of Edinburgh. He also heads the Biological Systems Unit at the Okinawa Institute of Science and Technology, Japan.
The rate of a chemical reaction is influenced by many different factors, such as temperature, pH, reactant, and product concentrations and other effectors. The degree to which these factors change the reaction rate is described by the elasticity coefficient. This coefficient is defined as follows:
Jens Georg Reich is a German scientist and a member of the German Ethics Council. He became famous as a civil rights campaigner in the last decade of the German Democratic Republic (GDR)
Tom Abraham Rapoport is a German-American cell biologist who studies protein transport in cells. Currently, he is a professor at Harvard Medical School and a Howard Hughes Medical Institute investigator. Born in Cincinnati, Ohio, he grew up in East Germany. In 1995 he accepted an offer to become a professor at Harvard Medical School. In 1997 he became an investigator of the Howard Hughes Medical Institute. He is a member of the American and German National Academies of Science.
Stefan Schuster is a German biophysicist. He is professor for bioinformatics at the University of Jena.
David A. Fell is a British biochemist and professor of systems biology at Oxford Brookes University. He has published over 200 publications, including a textbook on Understanding the control of metabolism in 1996.
Jan-Hendrik HofmeyrFRSSAf is one of the leaders in the field of metabolic control analysis and the quantitative analysis of metabolic regulation.
Control coefficients are used to describe how much influence a given reaction step has on the steady-state flux or species concentration level. In practice, this can be accomplished by changing the expression level of a given enzyme and measuring the resulting changes in flux and metabolite levels. Control coefficients form a central component of metabolic control analysis.
In biochemistry, a rate-limiting step is a step that controls the rate of a series of biochemical reactions. The statement is, however, a misunderstanding of how a sequence of enzyme catalyzed reaction steps operate. Rather than a single step controlling the rate, it has been discovered that multiple steps control the rate. Moreover, each controlling step controls the rate to varying degrees.