[TYPES/announce] research position at Imperial, process models for systems biology

[Philippa Gardner]

Luca Cardelli and I have a three-year postdoctoral research position 
available at Imperial, to apply process-modelling techniques to the 
signalling of phagocytosis (the process of ingesting and destroying a 
bacteria or other foreign matter by certain kinds of cells). This 
position complements two other positions: one for a biologist, the other 
for a mathematician. Our difficult challenge is to bridge the gap 
between the experimental work, a predictive  analysis using process 
models, and the very different analysis using  differential equations.

The details are given below: the deadline for applications is 10th 
February; please send informal enquiries to me.

I'd be grateful if you would forward this email  to candidates you think 
might be suitable. In particular, we are looking for someone  with 
either a background in biology or at least a strong interest in the subject.

Best wishes,

Philippa Gardner
pg at doc.ic.ac.uk

--------------------------------------------------------------


Research Assistant/Associate
Department of Computing, Imperial College London

Title: Computational Modelling of Biological Processes

Salary: £26,120 - £33,330 inclusive of London Allowance per annum

Deadline for Applications: 10th February 2006

Applications are invited for the position of a research
assistant/associate for up to three years to work on the application
of process-modelling techniques to the signalling of
phagocytosis. This position has been awarded to Dr Philippa Gardner
and Dr Luca Cardelli (Microsoft Research Cambridge), funded by a large
BBSRC/EPSRC grant to support a new Centre for Systems Biology at
Imperial. It complements two equivalent positions (one for a
biologist, one for a mathematician) in Centre for Molecular
Microbiology and Infection & Division of Cell and Molecular Biology,
to investigate the spatio-temporal control of phagocytic signalling
during uptake of bacteria. We expect the three researchers to work
closely together.

Formal applications should be sent  to the address at the end of this
message. Please send  informal enquiries to

Philippa Gardner, email: pg at doc.ic.ac.uk

Background of Project
----------------------

Recognition and uptake of bacteria, parasites and
encapsulated DNA vaccines by professional phagocytes - macrophages,
dendritic cells - is crucial for the induction of protective
immunity. Live attenuated strains of intracellular pathogens such as
Salmonella and Shigella have been shown to act as oral human and
animal vaccines and as heterologous vaccine carriers capable of
inducing protective responses to antigens from other viral, bacterial
and eukaryotic pathogens. The mechanism of attenuation is crucial in
determining vaccine efficacy, but the biology of this is unknown; in
practice multiple mutants are screened in an empirical trial and error
manner. It would be a major scientific advance if we were able to
engineer improved vaccine strains on the basis of a rational
understanding of the factors that determine their ability to stimulate
a protective, lasting immune response. This may now be possible
through a systems biology approach that can directly inform on logical
targets for mutagenesis studies.

Goals
-----

The project has the objective of modeling such a biological
system via process calculus techniques, and to augment the model as
new knowledge is gathered via experiments. Information derived from
modeling will be used to design new hypotheses to be tested in the
experimental system.

We will use process calculi to build a computer simulation of the
uptake event, feeding in information from the biology relating to
regulatory sequences, localization, and hierarchical issues. The
general approach of process calculi modeling consists in first
identifying appropriate discrete interactions that need to be modeled;
these can be as detailed as individual chemical events or as abstract
as membrane evolutions, or a combination of these. The basic
interactions are embedded, in a fairly systematic and well-understood
way, in a process language that also includes other general modeling
operators (such as concurrent or stochastic interactions). The
resulting modeling language can be used to describe and analyze
complex biochemical systems, particularly emphasizing discrete and
combinatorial aspects, in much the same way that a programming
language can be used to describe complex software systems. We will
build on previous work that uses stochastic process calculi for
modeling both ordinary biochemical interactions and the dynamic
evolution of compartments, particularly during endocytosis. The
modeling component of the project will involve identifying a suitable
modeling language, using it to encode the experimental knowledge of
pathogen uptake as it is being acquired, and running simulations of
the whole process, from the input stimuli to the formation and
evolution of the phagosome.


Applicants should complete an application form, downloadable from
http://www.imperial.ac.uk/employment/academicform.htm. Applications
will not be accepted unless they are on the correct form and clearly
marked with the Job Reference Number PG Bio 05.  The application form
should be accompanied by a full CV with names and addresses of 3
referee and should be sent to:

Mrs Nicola Rogers
Department of Computing
Imperial College London
South Kensington Campus
London, SW7 2AZ
UK
Email: n.c.rogers at imperial.ac.uk