Research Interests

I have over 15 years of experience in computational biology. My research goal is to predict the dynamic behaviour of the living cell by computer simulation of the genome scale network models representing experimental data on interaction between molecules.

I am convinced that we can fully exploit information about full genomic sequence of human and other organisms only if we use legacy of molecular biology data to build predictive mechanistic models of genotype-phenotype relationship. Due to the number of molecular components in the cell and non-linearity of their interactions this goal can only be achieved by computer simulation. The successful computer simulation of the molecular cell biology will enable prediction of the individual genetic differences on the trajectories of major diseases providing foundation for predictive and personalized medicine of the future. Likewise, industrial biotechnology is being revolutionized by increasing ability to computer simulate the effects of genetic engineering in commercial cell lines and therefore rationally design industrial fermentation processes.

Currently I am working on development of hybrid algorithms integrating Flux Balance Analysis (FBA) of quasi-steady state metabolic reaction networks and qualitative dynamic simulations of regulatory processes that cannot be model in steady state framework. In this work I capitalize on my expertise in the fields of constraint based modeling of genome scale metabolism and stochastic simulations of detailed kinetic models.

I have performed computational part of the project leading to the first reconstruction of the Genome Scale Metabolic Reaction Network of Mycobacterium tuberculosis, causative agent of Tuberculosis disease (Genome Biology, 2007). The tools developed for this project motivated have been matured into SurreyFBA software recently published by my group (Bioinformatics, 2011). I have also been working on analysis of gene expression data in the context of genome scale metabolic networks (PLoS Computational Biology, 2011) and development of software for web based computation with FBA models (BMC Bioinformatics, 2011). Industrial biotechnology is an important application area for genome scale metabolic modeling; I worked on FBA simulations in the context of bioprocess feed development for antibiotic production in Streptomyces coelicolor (Metabolic Engineering, 2008).

I have been modeling stochastic effects in molecular interaction network dynamics for 10 years. I have constructed detailed model of prokaryotic gene expression and investigated dependence between accuracy of gene expression and transcription and translation initiation rates (J. Biol. Chem, 2001). This work has also lead to the publication of STOCKS software for stochastic simulation of molecular interaction network (Bioinformatics, 2002). Subsequently, we have developed Maximal Timestep Method, a hybrid algorithm enabling stochastic simulation of systems with reaction rates varying by many orders of magnitude. The method has been applied to investigate propagation of gene expression noise to the level of metabolic processes leading to epigenetically inherited changes in single cell physiology (Biophysical Journal 2004). More recently, I was working the influence of RNA regulators on gene expression noise (Biophysical Journal 2009) and constructed stochastic kinetic model of Two Component System Signalling (Molecular Biosystems 2010).

In have past bioinformatics experience in the field of homology modeling of protein structure (Nucl. Acids. Research 2003, Nature Immunology 2003), regulatory sequence analysis (J. Biol. Chem 2005) and annotation of genome sequences (Nature 2004). I did my PhD in the area of Biophysics and worked on the agent-based simulations of protein crystal growth (Biophysical Journal 1997). I have also performed molecular dynamics simulations and analysed light scaterring spectra (J. Phys. Chem. 1999).

Publications

1. Sroka J, Krupa L, Kierzek AM, Tyszkiewicz J. CalcTav - Integration of a Spreadsheet and Taverna Workbench. Bioinformatics. 2011 (accepted for publication)
2. Bonde BK, Beste DJ, Laing E, Kierzek AM, McFadden J. Differential Producibility Analysis (DPA) of Transcriptomic Data with Metabolic Networks: Deconstructing the Metabolic Response of M. tuberculosis. PLoS Comput Biol. 2011 7(6):e1002060.
3. Sroka J, Bieniasz-Krzywiec L, Gwóźdź S, Leniowski D, Lącki J, Markowski M, Avignone-Rossa C, Bushell ME, McFadden J, Kierzek AM. BMC Bioinformatics. 2011 12:196.
4. Gevorgyan A, Bushell ME, Avignone-Rossa C, Kierzek AM. SurreyFBA: A command line tool and graphics user interface for constraint based modelling of genome scale metabolic reaction networks. Bioinformatics. 2011 27(3):433-4.
5. Lewis RA, Laing E, Allenby N, Bucca G, Brenner V, Harrison M, Kierzek AM, Smith CP. Metabolic and evolutionary insights into the closely-related species Streptomyces coelicolor and Streptomyces lividans deduced from high-resolution comparative genomic hybridization. BMC Genomics. 2010 11:682.
6. Kadir TA, Mannan AA, Kierzek AM, McFadden J, Shimizu K. Modeling and simulation of the main metabolism in Escherichia coli and its several single-gene knockout mutants with experimental verification. Microb Cell Fact. 2010 9:88.
7. Kierzek AM, Zhou L, Wanner BL.Stochastic kinetic model of two component system signalling reveals all-or-none, graded and mixed mode stochastic switching responses.Mol Biosyst. 2010 6(3):531-42.
8. Estorninho M, Smith H, Thole J, Harders-Westerveen J, Kierzek A, Butler RE, Neyrolles O, Stewart GR. ClgR regulation of chaperone and protease systems is essential for Mycobacterium tuberculosis parasitism of the macrophage. Microbiology. 2010 156:3445-55.
9. Beste DJV, Espasa M, Bonde B, Kierzek AM, Stewart GR, McFadden J The Genetic Requirements for Fast and Slow Growth in Mycobacteria PLoS ONE, 4(4): e5349. doi:10.1371/journal.pone.0005349 2009
10. Komorowski M, Miekisz J, Kierzek AM Translational repression contributes greater noise to gene expression than transcriptional repression. BIOPHYSICAL JOURNAL 96:372-384 2009
11. Khannapho C, Zhao H, Bonde BK, Kierzek AM, Avignone-Rossa CA, Bushell ME. Selection of objective function in genome scale flux balance analysis for process feed development in antibiotic production. METABOLIC ENGINEERING 2008 Metab Eng. 2008 10(5):227-33
12. Beste DJV, Hooper T, Stewart G, Bonde B, Avignone-Rossa C, Bushell ME, Wheeler P, Klamt S, Kierzek AM, McFadden J GSMN-TB: a web-based genome scale network model of Mycobacterium tuberculosis metabolism. GENOME BIOLOGY 8:R89 2007
13. Jacewicz A, Makiela K, Kierzek A, Drake JW, Bebenek A. The roles of Tyr391 and Tyr619 in RB69 DNA polymerase replication fidelity. J. MOL. BIOL. 368:18-29 2007
14. Bushell ME , Sequeira SIP, Khannapho C, Zhao HJ, Chater KF, Butler MJ, Kierzek AM, Avignone-Rossa CA The use of genome scale metabolic flux variability analysis for process feed formulation based on an investigation of the effects of the zwf mutation on antibiotic production in Streptomyces coelicolor ENZYME AND MICROBIAL TECHNOLOGY39 : 1347-1353 2006
15. Sroka J, Kaczor G, Tyszkiewicz J, Kierzek AM XQTav: an XQuery processor for Taverna environment. BIOINFORMATICS 22(10):1280-1281 2006
16. Zaim J, Speina E, Kierzek AM Identification of new genes regulated by the Crt1 transcription factor, an effector of DNA-damage checkpoint pathway in Saccharomyces cerevisiae J BIOL CHEM 280:28-37 2005
17. Hamimes S, Arakawa H, Stasiak AZ, Kierzek AM, Hirano S, Yang YG, Takata M, Stasiak A, Buerstedde JM, Van Dyck E RDM1, a novel RNA recognition motif (RRM)-containing protein involved in the cell response to cisplatin in vertebrates. J. BIOL. CHEM. 280: 9225-9235 2005
18. Caldwell RB, Kierzek AM, Arakawa H, Bezzubov Y, Zaim J, Fiedler P, Kutter S, Blagodatski A, Kostovska D, Koter M, Plachy J, Carninci P, Hayashizaki Y, Buerstedde JM. Full-length cDNAs from chicken bursal lymphocytes to facilitate gene function analysis. GENOME BIOLOGY 6(1):R6. 2005
19. Wahl MB, Caldwell RB, Kierzek AM, Arakawa H, Eyras E, Hubner N, Jung C, Soeldenwagner M, Cervelli M, Wang YD, Liebscher V, Buerstedde JM. Evaluation of the chicken transcriptome by SAGE of B cells and the DT40 cell line. BMC GENOMICS 5(1):98 2004.
20. Kierzek AM Simulation of Biochemical Networks. In Genetics, Genomics, Proteomics and Bioinformatics. John Wiley & Sons (review).
21. International Chicken Genome Sequencing Consortium (Kierzek AM is included on the list of authors). Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. NATURE 432(7018):695-716. 2004
22. Puchalka J, Kierzek AM Bridging the gap between stochastic and deterministic regimes in the kinetic simulations of the biochemical reaction networks. BIOPHYS J, 86:1357-1372 2004
23. Zaim J, Kierzek AM Domain organization of activation-induced cytidine deaminase. NATURE IMMUNOLOGY 4(12):1153 2003
24. Zaim J, Kierzek AM The structure of full-length LysR-type transcriptional regulators. Modeling of the full-length OxyR transcription factor dimer. NUCLEIC ACIDS RESEARCH 31(5):1444-1454 2003
25. Speina E, Kierzek AM, Tudek B Chemical rearrangement and repair pathways of 1,N(6)- ethenoadenine. MUTATION RESEARCH 29;531(1-2):205-17. 2003
26. Kierzek AM STOCKS: STOChastic Kinetic Simulations of biochemical systems with Gillespie algorithm. BIOINFORMATICS 18(3): 470-481 2002
27. Kierzek AM, Zaim J, Zielenkiewicz P The effect of transcription and translation initiation frequencies on the stochastic fluctuations in prokaryotic gene expression J BIOL CHEM 276: (11) 8165-8172 2001
28. Kucharczyk R, Kierzek AM, Slonimski PP, et al. The Ccz1p interacts with Ypt7 GTPase in the process of fusion of multiple transport intermediates with the vacuole in S.cerevisiae. J CELL SCI 114 (17): 3137-3145 2001
29. Kierzek AM, Zielenkiewicz P Models of protein crystal growth (Review) BIOPHYS CHEM 91: (1) 1-20 2001
30. Georgalis Y, Kierzek AM, Saenger W Cluster formation in aqueous electrolyte solutions observed by dynamic light scattering J PHYS CHEM B 104: (15) 3405-3406 2000
31. Kierzek AM, Pokarowski P, Zielenkiewicz P Microscopic model of protein crystal growth BIOPHYS CHEM 87: (1) 43-61 SEP 15 2000
32. Plochocka D, Kierzek A, Obtulowicz T, et al. 3-methyladenine-DNA glycosylase I from Escherichia coli - Computer modeling and supporting experimental evidence BIOCHEM BIOPH RES CO 268: (3) 724-727 2000
33. Kierzek AM, Pokarowski P, Zielenkiewicz P Lattice simulations of protein crystal formation BIOPHYS CHEM 77: (2-3) 123-137 1999
34. Kierzek AM, Wolf WM, Zielenkiewicz P Simulations of nucleation and early growth stages of protein crystals BIOPHYS J 73: (2) 571-580 1997
35. Kaczanowski S, Kierzek AM, Zielenkiewicz P, Shuffling algorithm for protein design. PROTEIN PEPTIDE LETT 6 (2): 99-104 1999
36. Gora-Sochacka A, Kierzek A, Candresse T, Zagórski-Ostoja W. The genetic stability of potato spindle tuber viroid (PSTVd) molecular variants RNA 3: (1) 68-74 1997
37. Kierzek A, Zielenkiewicz P Energy minimization of globular proteins with solvent effects included. Comparison of empirical solvation energy terms and explicit water treatment ACTA BIOCHIM POL 44 (3): 549-556 1997
38. Kierzek A, Plochocka D, Zielenkiewicz P Molecular recognition theory applied to proteinprotein interaction but not to protein folding (letter to editor) NATURE MEDICINE 1(12):1222-3 1995
39. Moraczewski IR, Borkowski W. Kierzek, A. Clustering geobotanical data with the use of a genetic algorithm. COENOSES 10: 17-28 1995

Teaching

1. BMS3072: Systems Biology: Genomes in Action
2. BMS1023: Numeracy skills and Statistics
4. MSc Coourses: Statistics

Departmental Duties

Professor of Systems Biology

Module organiser for BMS3072

Grants

1. EraSysBio+/BBSRC grant “Integration of modeling with transcription and gene essentiality profiling to study interaction of MTB bacillus with macrophages and dendritic cells” PI and international consortium coordinator: Dr Andrzej M. Kierzek Co-investigators: Graham Stewart (University of Surrey), Johnjoe McFadden (University of Surrey), Olivier Neyrolles (CNRS, France), Ludovic Tailleux (Institute Pasteur, France), Steffen Klamt (Max Planck Institute Germany), Maria Foti (University Milan-Biocca, Italy). Amount for University of Surrey: £495,173 Entire consortium award €1,260,501, Start: 01/03/2010, End: 28/02/2013 (36 months)
2. BBSRC grant "Predictive Analysis of Network Activation in Response to Lipid Loading in the Liver". PI: Dr Bernadette J. Moore, Co-applicants: Dr Andrzej M.Kierzek, Dr Nick Plant. Amount: £498.809. Start: 01/04/2011 End: 01/04/2014
3. Wellcome Trust grant “Investigation of metabolism and substrate utilization of Mycobacterium Tuberculosis”, PI: Johnjoe McFadden, Co-applicants: Andrzej M. Kierzek, Graham Stewart, Dany Beste amount: £405,329 Start: 01/09/2009, End 30/08/2011 (36 months)
4. BBSRC grant: "In silico study of lignocellulosic biofuel processes.". PI: Professor Michael Bushell Co-applicants: Dr Andrzej M. Kierzek, Dr Claudio Avignone-Rossa. Amount: £107,059. Start: 01/05/2009. End: 01/05/2012