At 12:15 05/01/01 -0000, Douglas Kell wrote:
>Actually I am very favourably disposed to the e-cell type of project,
>and I am hopnig that the UK can start one (it will also bring in all
>the mol biol people who want to get into /metabolic modelling but
>don't know the right people to hold their hands).
>I think this is a good idea too. What about organising a UK consortium and
approaching the Wellcome Trust?
>(Comment: the next generation of metabolic models, which will
>probably be integrated with genomics databases, would do well to
>include fields containing information on the EVIDENCE for particular
>values, see e.g. Evidence Codes in Gene Ontology
>http://www.geneontology.org/GO.evidence.html).
This is an excellent idea.
>(iii) There is a view that says that kinetics as measured in vitro or
>even in situ are so different from those occuring under the actual
>environmental conditions in vivo that they should not be treated as
>much better than estimates anyway, and that that will NEVER change.
>In which case we shouldn't worry about dotting the last i, etc.
This prompts a question about what would be the best stategy for such a model.
It is possible to have a "top-down" strategy to cell modelling (by
analogy to top-down strategies in MCA) i.e. measure some key
intermediates or branch-point metabolites within the cell (by NMR, HPLC or
whatever), make a range of perturbations at known places in metabolism, and
extract the phenomenological kinetics of the pathways of interest.
This generates a simple phenomenological model of metabolism.
(The same approach may be used on protein or mRNA levels.)
There are many advantages and disadvantages of this approach compared to
a "bottum-up" approach starting from the kinetics of isolated enzymes,
but in principle one can work down to the enzyme level by refining the
model with more intermediates, and it may be experimentally more approachable.
(Indeed there is already substantial data to generate such models).
The other tricky problem is what type of cell to use. Everybody would
have theirown favorite.
Guy Brown
Dr Guy C. Brown
Department of Biochemistry,
University of Cambridge,
Tennis Court Road,
Cambridge CB2 1QW, UK.
Tel: (44) (0)1223 333342
Fax: (44) (0)1223 333345
e-mail: gcb at mole.bio.cam.ac.ukhttp://www.bio.cam.ac.uk/dept/biochem/brown
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