József Bruck, Ph.D. Private Mobile E-mail Balzac. u. 43, H-1136 Budapest +36/ 30/ 853 0725 [email protected] Affiliation Institute f. Bichemistry and Molecular Biology University of Debrecen (Guest Researcher) Education 4. May 2012 Oct. 2011 2007 - 2011 2006 - 2007 Doctoral student of biophysics at Humboldt University Berlin, Germany Ph.D. Defence. Final grade: magna cum laude Submission of Ph.D. thesis Supervisor: Prof. Edda Klipp Supervisor: Prof. Reinhardt Heinrich (passed away) 1995 - 2003 Student of physics at the University of Vienna, Austria Academic degree: magister rerum naturalium, (M.Sc. equivalent) grade: cum laude (original term: Mit Auszeichnung bestanden) Thesis title (translated): On Some Aspects of Taub-NUT Spacetime, completed in the Gravity Research Group, Institute for Theoretical Physics 1997 - 1998 Erasmus exchange year at the University of Wales Swansea, Swansea, UK 1991 - 1995 Secondary school: Bundes-Oberstufenrealgymnasium 3, Vienna, Austria. Final exam grade: cum laude (original term: Mit ausgezeichnetem Erfolg) 1982 - 1991 Elementary and secondary school in Budapest, Hungary Professional experience 1. Nov. 2012 31. Mai 2013 Research fellow at the Laboratory of Protein Dynamics Institute for Biochemistry and Molecular Biology University of Debrecen Tasks: Bioinformatics research, computer administration and teaching Jan. - July 2010 Graduate researcher in the EU project UNICELLSYS Sept. - Nov. 2009 Visiting researcher at VTT Research Centre of Finland, Cell Factory group, Biotechnology Division June 2005 Dec. 2008 Pre-doctoral Marie Curie fellow in the Systems Biology Project Analysis of the evolutionary design of metabolic networks in the Theoretical Biophysics Group, Department of Biology, Humboldt University Berlin. 2007 - 2008 Stays at MPI Molecular Genetics and MPI for Molecular Plant Physiology Nov. 2004 Jan. 2005 Internship at Prof. Peter Schuster’s Theoretical Biochemistry Group, Institute of Theoretical Chemistry, University of Vienna, Austria Supervision: Dr. Christoph Flamm Task: testing implementations of mRNA alignment and secondary structure algorithms Nov. 2003 Nov. 2004 Participation in a research project (cDNA Microarray Data Analysis) with Dr. Nikolaus Wick, Clinical Department of Pathology, General Hospital of Vienna, Austria Task: model simulation and Affymetrix data analysis Sept. 2000 Oct. 2002 Junior research assistant (15h - 440 EUR p. week) in the fMRI research group Prof. Roland Beisteiner at the Ludwig Boltzmann Institute of Functional Brain Topography General Hospital of Vienna, Vienna, Austria Task: computer aided data preparation of fMRI measurement data Selected courses during doctoral training Experimental 2 weeks practical course on methods of molecular biology (C. elegans) (title: Fachkurs Ecological Genomics), Institute f. Biology, Humboldt University (summer term 2007) Statistical Physics of Gene Regulation – from Networks to Expression Data and Back Heraeus International Summer School, Jacobs University Bremen, 16 - 27 July 2007 FEBS-SysBio2007: From Molecules to Life - FEBS advanced lecture course on systems biology Gosau, Austria, 10 - 16 March 2007 First Göteborg PhD course in quantitative yeast biology, Göteborg, Sweden, 6 - 16 June 2005 Research Interests Mathematical and computational modelling and data analysis for living systems. How does system behaviour emerge from component interactions? How can we describe and understand emergent behaviour through the interplay of theories and data? Research topics: Data-based kinetic modelling of biochemical networks; Network analysis (metabolic networks and other systems) Interests outside of present expertise: Metabolic networks in ecology; Quantitative sociology; Human societies as (the evolution of) agent interactions; Selection-based evolution Skills, Experience Mathematical tools: ordinary differential equation - based modelling, flux balance analysis, metabolic control analysis, network analysis/random graphs, statistical methods, statistical physics, linear programming, differential geometry/tensor calculus, Lie group theory Software tools: Programming active: Python, Matlab, R, Perl, Linux Shell; software tools in systems biology (Copasi, SBtoolbox2) previous experience: Mathematica, IDL, Teaching (undergraduate biophysics courses): Participation in the group's annual two-weeks course (taught units: Dynamical systems, Metabolic control analysis, Enzyme kinetics) Introductory undergraduate one-semester course on Statistical thermodynamics (with Thomas Hahndorf) Languages: Hungarian (native), German (close to native), English (fluent) Awarded grants “Einstein Young Scholars Programme” - grant for attendance of the Falling Walls Conference 2010 “Tuition waiver” - grant for attendance of the Complex Systems course organised within the Summer University 2009 program of the Central European University, Budapest, Hungary Reviewing work for In Silico Biology (ISB) Membership Hungarian Society for Bioinformatics Non-professional activities and interests Literature, music, travelling. I keep a pedestrian interest in some aspects of mathematics and linguistics. I enjoy various kinds of sports for recreation such as skiing and rowing. Work in the International Association of Physics Students (IAPS), and the Hungarian Association of Physics Students (Mafihe); Vice president of the organising committee of the ICPS2002, a student conference (over 200 participants); Organiser of the PSI international student meeting (30 participants). Publications, Manuscripts PhD thesis: On the Regulation of Central Carbon Metabolism in S. cerevisiae; Ph.D. thesis, Humboldt University, 2011. downloadable from http://jaguar.biologie.hu-berlin.de/~jbruck/ Manuscript in preparation: Comparing cell states using metabolic control analysis? A generalisation of the summation theorems for multiple steady states; J. Bruck, E. Klipp and J. Tóth Submitted manuscript: What controls metabolic flux changes between cell states? Revisiting kinetic modeling studies for central carbon metabolism in S. cerevisiae upon respiratory and fermentative growth. J. Bruck, J.-P. Pitkänen and E. Klipp Peer reviewed Publications Exploring the effect of variable enzyme concentrations in a kinetic model of yeast glycolysis; J. Bruck, W. Liebermeister, and E. Klipp; Genome Informatics, 20, 1-14, 2008 Patterns of Interactions of Reaction Pairs in Metabolic Networks; J. Bruck, O. Ebenhöh, and R. Heinrich; Genome Informatics 17, 208-218, 2006 Non-Uniform Hybridization is a Potential Source of Error in Oligonucleotide-Chip Experiments with Low Amounts of Starting Material; N. Wick, J. Bruck, E. Gurnhofer, C. W. Steiner, P. Giovanoli, D. Kerjaschki, S. Thurner; Diagnostic Molecular Pathology 13(3), 2004. Conference attendances Workshop Towards a Consensus Model of Yeast Glycolysis 21 - 25 Nov. 2011. Lorentz Center, Leiden, Netherlands (Participation was on invitation basis; no lectures were held) Data analysis using kinetic modelling – allosteric vs. transcriptional regulation in yeast carbon metabolism IX. Hungarian Conference on Biometrics, Biomathematics and Bioinformatics, 1 June 2011, Budapest, Hungary (in Hungarian) Falling Walls Conference, 2010 on 8 November 2010, Berlin, Germany (no presentation by attendees) A Data Driven Model of Yeast Glycolysis - from transcription to reaction kinetics (short talk) European Conference on Mathematical and Theoretical Biology; 29 June - 4 July 2008, Edinburgh, UK The Effect of Variable Enzyme Concentrations in a Kinetic Model of Yeast Glycolysis (conference talk) 8th International Workshop on Bioinformatics and Systems Biology; 9 - 11 June 2008, Zeuthen, Germany Data driven modelling of yeast glycolysis (conference talk) Cold Spring Harbor Laboratory Meeting on Computational Cell Biology; 29 - 30 March 2008; Hinxton, UK Network of Interacting Reactions in Metabolic Networks (poster) 12th BTK Meeting; 14 - 17 Sept. 2006, Trakai, Lithuania Network of Interacting Reactions in Metabolic Networks (conference talk) Large-Scale Random Graph Methods for Modeling Mesoscopic Behavior in Biological and Physical Systems; 28 Aug. - 4 Sept. 2006, Alfréd Rényi Institute of Mathematics of the HAS, Budapest, Hungary Patterns of Interactions of Reaction Pairs in Metabolic Networks (conference talk) 6th Annual International Workshop on Bioinformatics and Systems Biology; 24 - 26 July 2006, Boston, MA, USA Short abstracts coautorships (partly during undergraduate studies) Ex Vivo Heterogeneity of Lymphatic Endothelial Cells; N. Wick, et al.; Gordon Research Conference on Molecular Mechansisms in Lymphatic Function and Disease, Ventura, CA, USA, March 2004 Comparing Isolated and Simultaneous Movements for Presurgical Evaluation Purposes; A. Geissler et al. Neuroimage. 2002, CD, 8th Human Brain Mapping Meeting, June 2-6, 2002, Sendai, Japan Description of previous research Analysis of the evolution of internal disorder in protein domains This ongoing project started within and with the expertise of the Laboratory of Protein Dynamics is a largescale study aiming to further clarify how internal disorder connected to protein domains changes after the 'birth' of a domain. Thesis project The project associated with my thesis entitled On the Regulation of Central Carbon Metabolism in S. cerevisiae falls into the field of computational systems biology, focusing on analysing the regulation of yeast central carbon metabolism on the system level by means of mathematical modelling and computer simulations. To this end, a kinetic model of yeast glycolysis was constructed and fitted to fluxomics and metabolomics datasets. The data were produced using chemostat yeast cultures by Prof. Merja Penttilä's research division in VTT Technical Research Centre of Finland. Methodology for this work included the choice of a kinetic ordinarydifferentialequationbased model of appropriate complexity, identifying appropriate steadystate fluxes using constrained flux balance analysis, estimation of model parameters using experimental data, and interpreting the results. The computational tools included a specialized MATLAB toolbox utilized by scripts written by myself. Details of this work are described in Chpt. 4 of my Ph.D. thesis. Intermediate results were reported in (Bruck et al., 2008) and further publications are in progress. Since a thorough understanding of the experimental setting was necessary, I reviewed the equations describing growth of a microbial culture in a nutrient limited chemostat in Chapter 2 of my thesis. Here, I also deduced an exact characterisation of the selection pressure acting on the microbial population. Wile the scenario in the gut of a mammal is more complex, similar notions may be useful in describing microevolution due to selection pressure in this setting. Theorems of metabolic control analysis for multiple trajectories Theoretical considerations related to my thesis project have lead to the definition of new control coefficients. The aim is to allow the – hitherto infeasible – comparison of distinct steady states or trajectories within this framework, e.g. by introducing control coefficients for the flux difference between two steady states. During this work, I discovered a generalisation of the summation theorems to timedependent trajectories which have, to my knowledge, not been published so far. A manuscript reporting these results is in preparation. Network analysis Under the supervision of the late Prof. Reinhardt Heinrich, I conducted a study of genome wide metabolic stoichiometric networks defining ’patterns of interacting reactions’. Here, neighbourhood relationships were defined according to the nature of the stoichiometric link between two neighbouring reactions in a reaction network. The definition was inspired by the question whether proceeding of one reaction implies another reaction to proceed. We proposed to use these neighbourhood relationships as a novel concept of adjacency in large scale graph theoretical analyses of metabolism. The resulting formalism was applied to conduct a genomescale structural analysis on a set of nearly 5000 metabolic reactions stored in the KEGG database. Strongly connected components of the resulting directed graph were identified. Some results were reported in (Bruck et al., 2006). Diploma thesis My diploma thesis On some properties of the TaubNUT spacetime (original in German) was concerned with the TaubNUT spacetime, a known solution of the Einstein field equations, the system of partial differential equations of the general theory of relativity. This solution is defined by certain symmetry properties, effectively restricting the dynamics to ordinary differential equations. The work contains a description of the theory of Liegroup actions formalising the notion of symmetries. Closing an apparent gap in the literature, the uniqueness of the known parametrised solution of the ordinary differential equation system associated with this spacetime was proven. References Prof. Dr. Dr. h.c. Edda Klipp (Supervisor) Dr. Juha-Pekka Pitkänen (Collaborator) [email protected] [email protected] Group of Theoretical Biophysics Institut for Biology, Humboldt University Berlin Invalidenstraße 42 D-10115 Berlin, Germany Group leader “Cell factory” Biotechnology Division VTT Technical Research Centre of Finland Tietotie 2, 02150 Espoo, Finland Prof. László Fésüs, D.Sc., M.H.A.S Director, Inst. f. Biochemistry and Molecular Biology, University of Debrecen Life Science Building Egyetem tér 1 H-4010 Debrecen, Hungary
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