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From genes to whole organs: vertical integration using mathematical simulation of the heart

Presented by: 
D Noble [Oxford]
Friday 28th September 2001 - 10:00 to 11:00
INI Seminar Room 1
Session Title: 
Vertical Integration in Biology: From Molecules to Organisms
Biological modelling of cells, organs and systems has reached a very significant stage of development. Particularly at the cellular level, there has been a long period of iteration between simulation and experiment (Noble & Rudy, 2001). We have therefore achieved the levels of detail and accuracy that are required for the effective use of models in drug development. To be useful in this way, biological models must reach down to the level of proteins (receptors, transporters, enzymes etc), yet they must also reconstruct functionality right up to the levels of organs and systems. This is now possible and three important developments have made it so:
  • Relevant molecular and biophysical data on many proteins and the genes that code for them is now available. This is particularly true for ion transporters (Ashcroft, 2000) The complexity of the biological processes that can now be modelled is such that valuable counter-intuitive predictions are emerging (Noble & Colatsky, 2000). Multiple target identification is also possible.
  • Computer power has increased to meet the demands. Even very complex cell models involving up to 50 different protein functions can be run on single processor machines, while parallel computers are now powerful enough to enable whole organ modelling to be achieved. (Kohl et al 2000)

    I will illustrate these points with reference to models of the heart.

    The criterion that models must reach down to the level of proteins automatically guarantees that they will also reach down to the level of gene mutations when these are reflected in identifiable changes in protein function (Noble 2001). Changes in expression levels characteristic of disease states can also be represented. These developments ensure that it will be possible to use simulation as an essential aid to patient stratification. I will illustrate these points with reference to sodium channel mutations.

  • University of Cambridge Research Councils UK
        Clay Mathematics Institute London Mathematical Society NM Rothschild and Sons