
Prof. Dr. Stefan Schuster
Research
Synopsis of current work in research
My scientific work is in the field of mathematical modelling of
biological processes, with the following major topics:
Structural analysis of biochemical networks.
I am interested in structural
properties of biochemical networks such as non-negative conservation
relations,
the set of all non-negative steady-state fluxes and elementary modes
of functioning. An elementary mode is
a minimal set of enzymes that can operate at steady state, with all the
irreversible reactions operating in the
appropriate direction (Schuster and Hilgetag, 1994, see publication
list below). Elementary modes can be
interpreted as biochemical pathways. Together with
David Fell, Claus
Hilgetag, John Woods, and
Thomas Pfeiffer,
we have developed algorithms and computer programs for detecting these
patterns in networks of any complexity,
for example, the program
METATOOL,
which can be downloaded from that site and an archive in
Oxford.
The algorithm for computing all elementary modes in biochemical
networks of any complexity can be downloaded
as a
PDF file.
There is also a version that
can be used online:
phpMetatool.
It was developed by Hagen Hoepfner and
Matthias Lange in Magdeburg.
Recently, I am trying to apply such topological methods to the
reconstruction of bacterial metabolism, in cooperation
with
Dr. Peer Bork's
group, in particular with
Thomas Dandekar
(University of Wuerzburg and EMBL, Heidelberg).
Another application is in metabolic engineering, where it is of
interest to find biochemical synthesis routes allowing a
maximal conversion yield.
Another method developed concerns the block-diagonalization of the
null-space matrix. This allows one to decompose
biochemical networks into subsystems that are completely independent
with respect to flux. This procedure is performed
by the program BlocDiag written in C by
Ferdinand Moldenhauer
and myself. It can be downloaded by
ftp.
Metabolic Control Analysis.
This analysis was developed in
the early 70's by Drs.
Heinrich
& Rapoport in Berlin and Drs. Kacser & Burns in
Edinburgh (for a
comprehensive bibliography established by
Athel Cornish-Bowden (Marseille),
click here).
My contributions concerned the analysis of flux control
insusceptibility (with Ronny Schuster), comparison of the
existing definitions of control coefficients (with Reinhart Heinrich),
and further elaboration on a modular approach
to control analysis (with
Daniel Kahn and
Hans Westerhoff).
Furthermore, I worked out a proof of an invariance
property of co-response coefficients and appropriate definitions of
control coefficients in nonideal systems and on
control analysis of metabolic systems involving quasi-equilibrium
reactions (with Johann Rohwer, Hans Westerhoff,
B.N. Kholodenko and
Marta
Cascante). I elaborated
on a method for phrasing the fundamental equations of MCA
in terms of generalized variables.
Further work
Further work concerns the study
of optimal properties of enzymatic systems (maximization of catalytic
efficiency, stability)
and the interrelation of transmembrane potential and pH difference
across membranes with electrogenic proton pumps.
I have also been involved in the development of models for calcium
oscillations and their interrelations with ER membrane
potential oscillations (in collaboration with Milan Brumen and Marko
Marhl from Maribor, Slovenia).