As an experimentalist with great interest, but little capabilities,
in modelling I would like to drop my penny on why MCA has not become
mainstream in the US. While I agree with almost everything that has been
mentioned I would like to add one more factor: Grants.
If my own experience in this area is any indication this is a major
reason. Most research in the US is entirely dependent on soft money and
people like myself, who only have jobs as long as the universities
accountant is happy with the overhead, cannot afford to branch off in a
non-grantable direction. Three times I submitted proposals containing MCA
or related approaches. Two of these were aimed at specific announcements
from granting agents encouraging these approaches. The one not aimed at an
announcement came back with :"These results cannot be interpreted." on the
part that I proposed to analyze using MCA. Never mind 10 quotations
demonstrating the feasibility. The two written in response to announcements
were in fact even more disappointing. The end, as far as I was concerened,
of one very MCA oriented "call for preproposals" was a letter that only
projects looking at gene expression would be considered. As if no one works
on gene expression. The other aimed at NIH PA-95-087 ended in the hands of
a study section with no knowledge of and clearly no affinity for the aims
of the announcement. If any of these had been granted there would have been
at least one post-doc in the US doing MCA related work.
The program director responsible for the grant that does pay my
research explained me a few facts of life : My experience with program
announcements and other initiatives is not unique. Mixing theory and
experimental work is bound to lead to rejection because the top 30 %
(everybody involved in the system mentions that number) is so good that
study sections will look for any reason to reject. Theoretical work is then
said to be out of scope. He told me not to mention MCA in future proposals
unless I have preliminary results that are so utterly convincing that even
the most hard-nosed experimentalist will be impressed. That sort of results
one can only get by spending some serious time and money on it, which you
cannot do without a grant specifically for it. Which rounds the circle.
Re: point of regulation
If I still may come back to this older discussion. I hope someone
can explain me some data (Microbiology 1996 142, 3337-3345). The specific
activity of inorganic pyrophospate dependent phosphofructokinase (PPi-PFK)
of Trichomonas vaginalis, catalyzing a reaction close to equilibrium
(because PPi instead of ATP is utilized), correlates better to glucose
consumption than that of any other glycolytic enzyme. Correlation obviously
is no proof of a causal relationship. However, no correlation is a much
stronger indication for the lack of it. Can this correlation be interpreted
as "exerting a high degree of flux control", even in the case of a close to
equilibrium reaction or is that stretching too far ?.
Thanks for your thoughts,
Benno
