Andrzej M Kierzek

Andrzej M Kierzek
University of Surrey · Department of Microbial and Cellular Sciences

PhD

About

150
Publications
13,311
Reads
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6,358
Citations
Citations since 2016
33 Research Items
2350 Citations
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
Additional affiliations
August 2004 - present
University of Surrey
Description
  • Professor of Systems Biology

Publications

Publications (150)
Article
Full-text available
The AbsA1-AbsA2 two component signalling system of Streptomyces coelicolor has long been known to exert a powerful negative influence on the production of the antibiotics actinorhodin, undecylprodiginine and the Calcium-Dependent Antibiotic (CDA). Here we report the analysis of a ΔabsA2 deletion strain, which exhibits the classic precocious antibio...
Article
Full-text available
Non-alcoholic fatty liver disease (NAFLD) is a serious public health issue associated with high fat, high sugar diets. However, the molecular mechanisms mediating NAFLD pathogenesis are only partially understood. Here we adopt an iterative multi-scale, systems biology approach coupled to in vitro experimentation to investigate the roles of sugar an...
Preprint
Full-text available
The AbsA1-AbsA2 two component signalling system of Streptomyces coelicolor has long been known to exert a powerful negative influence on the production of the antibiotics actinorhodin, undecylprodiginine and the Calcium-Dependent Antibiotic (CDA). Here we report the analysis of a ΔabsA2 deletion strain, which exhibits the classic precocious antibio...
Article
We present a new distributed architecture allowing simulation of living cells in spatial structures. Each cell is represented with a Quasi-Steady State Petri Net that integrates dynamic regulatory network expressed with a Petri net and Genome Scale Metabolic Network (GSMN) where linear programming is used to explore the steady-state metabolic flux...
Article
Full-text available
The scope of Physiologically Based Pharmacokinetic (PBPK) modelling can be expanded by assimilation of the mechanistic models of intracellular processes from Systems Biology field. Genome Scale Metabolic Networks (GSMNs) represent a whole set of metabolic enzymes expressed in human tissues. Dynamic models of the gene regulation of key drug metaboli...
Conference Paper
Development of a dynamic multi-scale, computational model of human hepatic glucose and fructose metabolism - Volume 75 Issue OCE3 - E.M. Maldonado, M.J. Tindall, N.J. Plant, A.M. Kierzek, J.B. Moore
Article
Full-text available
Systems Biology has established numerous approaches for mechanistic modelling of molecular networks in the cell and a legacy of models. The current frontier is the integration of models expressed in different formalisms to address the multi-scale biological system organisation challenge. We present MUFINS software, implementing a unique set of appr...
Article
Full-text available
Unlabelled: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, al...
Conference Paper
We present a tool for simulation of populations of living cells interacting in spatial structures. Each cell is modelled with the Quasi-Steady Petri Net that integrates dynamic regulatory network expressed with a Petri Net (PN) and Genome Scale Metabolic Networks (GSMN) where linear programming is used to explore the steady-state metabolic flux dis...
Article
HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction...
Article
Full-text available
A major roadblock in the effective treatment of cancers is their heterogeneity, whereby multiple molecular landscapes are classified as a single disease. To explore the contribution of cellular metabolism to cancer heterogeneity, we analyse the Metabric dataset, a landmark genomic and transcriptomic study of 2,000 individual breast tumours, in the...
Article
Full-text available
An understanding of the dynamics of the metabolic profile of a bacterial cell is sought from a dynamical systems analysis of kinetic models. This modelling formalism relies on a deterministic mathematical description of enzyme kinetics and their metabolite regulation. However, it is severely impeded by the lack of available kinetic information, lim...
Article
Full-text available
Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRAC...
Article
Background: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will im...
Article
Full-text available
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large scale genotyping and imputation in 25,723 PrCa cases and 26,274 controls of European ancestry.We detected evidence for multiple independent sign...
Article
Full-text available
Background Mycobacterium tuberculosis continues to kill more people than any other bacterium. Although its archetypal host cell is the macrophage, it also enters, and survives within, dendritic cells (DCs). By modulating the behaviour of the DC, M. tuberculosis is able to manipulate the host’s immune response and establish an infection. To identify...
Article
Full-text available
Non-alcoholic fatty liver disease (NAFLD) is a progressive disease of increasing public health concern. In western populations the disease has an estimated prevalence of 20%-40%, rising to 70%-90% in obese and type II diabetic individuals. Simplistically, NAFLD is the macroscopic accumulation of lipid in the liver, and is viewed as the hepatic mani...
Article
Full-text available
Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of >10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations...
Article
Full-text available
Leprosy has afflicted humankind throughout history leaving evidence in both early texts and the archaeological record. In Britain, leprosy was widespread throughout the Middle Ages until its gradual and unexplained decline between the 14th and 16th centuries. The nature of this ancient endemic leprosy and its relationship to modern strains is only...
Chapter
Recent experiments have shown the relevance of stochastic fluctuations to numerous biological phenomena. Intrinsic and extrinsic sources of noise existing at the subcellular level are capable of influencing the population dynamics and are believed to be responsible for the appearance of different phenotypes in clonal bacterial populations. Single c...
Article
Full-text available
Dynamic simulation of genome-scale molecular interaction networks will enable the mechanistic prediction of genotype-phenotype relationships. Despite advances in quantitative biology, full parameterisation of whole-cell models is not yet possible. Simulation methods capable of using available qualitative data are required to develop dynamic whole-c...
Article
Full-text available
The Mycobacterium tuberculosis complex includes bovine and human strains of the tuberculosis bacillus, including Mycobacterium tuberculosis, Mycobacterium bovis and the Mycobacterium bovis BCG vaccine strain. M. bovis has evolved from a M. tuberculosis-like ancestor and is the ancestor of the BCG vaccine. The pathogens demonstrate distinct differen...
Article
Full-text available
One of the most challenging problems in microbiology is to understand how a small fraction of microbes that resists killing by antibiotics can emerge in a population of genetically identical cells, the phenomenon known as persistence or drug tolerance. Its characteristic signature is the biphasic kill curve, whereby microbes exposed to a bactericid...
Article
Full-text available
Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we pr...
Data
Used methods for integration of KEGG pathways towards the biosynthesis of secondary metabolites. To integrate the KEGG pathways for secondary metabolite biosynthesis in all 38 actinobacterial models, compound-specific Python scripts were written which used our in-house PyModelEditor to edit the models in such a way that they would allow simulation...
Data
Correlation between reaction presence/absence and maximum fluxes. For each compound, this table shows the squared correlation coefficient (r2) of the absence/presence of reactions in a metabolic model and the maximum flux obtained during flux balance analysis. The reaction name is the name as it is given in the SEED database, and the reaction formu...
Article
Full-text available
Streptomycetes sense and respond to the stress of phosphate starvation via the two-component PhoR–PhoP signal transduction system. To identify the in vivo targets of PhoP we have undertaken a chromatin-immunoprecipitation-on-microarray analysis of wild-type and phoP mutant cultures and, in parallel, have quantified their transcriptomes. Most (ca. 8...
Article
Full-text available
Phenotypic differences of genetically identical cells under the same environmental conditions have been attributed to the inherent stochasticity of biochemical processes. Various mechanisms have been suggested, including the existence of alternative steady states in regulatory networks that are reached by means of stochastic fluctuations, long tran...
Data
Microarray data and analysis for known mutants, assessment of bias in data and ROC analysis. An Excel file containing TraSH data for mixes of known mutants, an assessment of bias within the TraSH data and receiver operating characteristic (ROC) analysis.
Data
Flux variable analysis. An Excel file containing maximal and minimal reaction fluxes compatible with maximal flux to biomass were computed for minimal media agar and serum.
Article
Full-text available
Neisseria meningitidis is an important human commensal and pathogen that causes several thousand deaths each year, mostly in young children. How the pathogen replicates and causes disease in the host is largely unknown, particularly the role of metabolism in colonization and disease. Completed genome sequences are available for several strains but...
Article
Full-text available
Taverna workbench is an environment for construction, visualization and execution of bioinformatic workflows that integrates specialized tools available on the Internet. It already supports major bioinformatics services and is constantly gaining popularity. However, its user interface requires considerable effort to learn, and sometimes requires pr...
Data
Metabolites that are shared between different experimental conditions (Venn diagram, Figure 4) associated with up-regulated M. tuberculosis genes. (XLS)
Data
Metabolites that are shared between different experimental conditions (Venn diagram, Figure 4) associated with down-regulated M. tuberculosis genes. (XLS)
Data