Download This project aims to investigate the use of Petri Nets to model

Modeling regulatory responses to stress in Bacillus subtilis
using Petri Net technology
This project aims to investigate the use of Petri Nets to model complex bacterial
regulatory systems. Developments in post-genomic technology are providing genome
wide data enabling the holistic modelling of complex cellular regulatory systems. In
particular gene-expression arrays and new proteomics techniques are producing large
datasets from studies of molecular processes. New approaches to the analysis of
genome-wide data are required to allow data driven models for hypothesis generation,
in silico data modelling and simulation to be generated.
B. subtilis represents an excellent model organism in which to study global
regulatory networks of bacteria. B. subtilis is one of the most genetically amenable
and intensively studied bacteria. The entire genome sequence was determined in 1997
(partly by us) and consortium for the systematic analysis of the function of unknown
B. subtilis genes has generated a collection distinct integrational, reporter gene
mutants in all genes of unknown function, a unique biological resource. With funding
from the BBSRC (PRES Initiative), 2 BBSRC Studentships and EU FW5 (Quality of
Life), Newcastle is coordinator of a consortium of 10 European laboratories with the
primary objective of defining the global regulatory networks of B. subtilis. The
regulatory networks group at Newcastle (Prof. Harwood, Dr. Wipat, Dr. Ward and
Dr. Glassey) have established an extensive knowledge base that describes complex
regulatory mechanisms that occur in this model Gram-positive microorganism in
response to phosphate and energy stress. Phosphate starvation is sensed via a two
component regulatory system primarily mediated by PhoPR whilst the general stress
response regulon is mediated by the sigma factor, B.
This project will investigate the use of Petri Nets as a new computational method
to model the phosphate response regulon in B. subtilis and to characterise its interplay
with the general stress (sigma B) response regulon. Data will be drawn from our
laboratory based studies of the transcriptome, proteome and phosphoproteome. Petri
Nets are a formal modelling technique based on using simple graph-like structures to
represent complex distributed interactions. They were originally developed for
modelling and reasoning about complex distributed computing applications, and have
the important advantage of being supported by a wide range of analysis tools (such as
those based on model checking). Petri Nets lend themselves (particularly stochastic
and coloured Petri Nets) to representing the kinds of relations and interconnections
that occur in metabolic/regulatory networks, and thus provide a formal means of
documenting and analysing the complex relationships that exist between genes,
substrates and proteins. Newcastle is a leading international centre for research on
Petri Nets, as exemplified by it recently hosting the prestigious Petri Net Conference:
Applications and Theory of Petri Nets’2001. In key EPSRC funded projects,
researchers are considering both the theoretical foundations (such as problems of
compositionality, time Petri Nets, analysis tools) and practical applications (such as
VLSI circuit design and programming language development) of Petri Net techniques.