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

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