ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

Furthermore, the values are spread out within this interval, thus indicating that there is
no sharp distinction between ‘important’ and ‘unimportant’ parameter combinations and
confirming the sloppy nature of the model under investigation [5]. The results presented
in [5] suggest that sloppy sensitivity spectra, as observed by the sustantial variation in
eigenvalue magnitudes in the model presented here, are universal in systems biology
models. This prevalence of sloppiness highlights the power of collective fits and
suggests that the focus of modelling efforts should be on predictions rather than on
parameters.
In summary, we have shown how a relatively simple system of differential equations
can accurately model the biological process of subventricular neurogenesis and that the
individual parameter values of this system are of equal importance in determining the
properties of its solutions. We have found a particular parameter space (which is likely
not to be unique) that is stable to perturbation and that yields results which match others
in the literature. We compared different mechanisms of migration and found that
chemoattraction is required to obtain physiologically relevant migration into the OB and
that chemorepulsion can fortify this migration pattern. We believe that this model could
be extended and reapplied once more accurate information on the various parameters is
available in order to make quantitative predictions of neurogenic behaviour.
Furthermore, the agreement between this model and the BLI data implies that at least
one chemoattractant factor is secreted in an endocrine/paracrine manner and is
responsible for directing migration, as it is produced by all types of neural stem cells
present. Whether this is physiologically the case remains to be confirmed
experimentally.
5. ACKNOWLEDGEMENTS
The authors would like to thank the Nuffield Foundation for the award of an
Undergraduate Research Bursary (Grant Refs: URB/ 39423, URB/37878) which
supported this research.
6. REFERENCES
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