Biochemie-Zentrum der Universität Heidelberg (BZH)

Funding
Sonderforschungsbereich (SFB) 638:
Dynamics of macromolecular complexes in biosynthetic transport
Chairman: Felix Wieland, Biochemie-Zentrum der Universität Heidelberg (BZH)
Cells are highly dynamic structures that can be
compared with factories full of sophisticated ma-
chines. In the last decades many individual parts
of these machines have been identified and char-
acterised. In the years to come the most excit-
ing challenge will be to decipher how individual
building blocks are put together in variable ways
to perform the cell´s dynamic functions. This is
done in an iterative way: one first tries to com-
bine the single parts to functional assemblies;
once an assembly is defined functionally, such
assemblies are combined to even higher aggre-
gates at a next layer of complexity, again func-
tionally characterised, and so on. With a hundred
thousand or so different proteins that build up a
human cell, and up to 200 parts comprising a
macromolecular complex (a functional unit), it is
evident that there is still a long way to go in order
to completely understand not only the compositions
of all possible functional units, but also their
interplay, i.e. their dynamics. With this knowledge
complete, we would understand the molecular
basis of life, and to prove our understanding, we
would have to reconstitute a living cell from its
defined building blocks. This would have to occur
not only by adding each component in exactly
the correct concentration, but also in a defined
sequence, because of their dynamics many of the
assemblies can only function correctly in a timedependent
manner. Needless to say that such a
task could be solved only by the activity of many
scientists worldwide, and final success, if possible
at all, lies in the far future.
Along this way, the SFB 638 “Dynamics of Macromolecular
Complexes in Biosynthetic Transport”
has initiated an interdisciplinary approach to investigate
the structural and dynamic behaviour of
complexes of up to 100 or so components with-
in a cell. Even if none of the scientists involved
is likely to reach the final goal, we believe that
many important lessons can be learned during
this journey. The expertise existing in Heidelberg
has led us to focus our research on biosynthetic
transport. In this context we use the term dynamics
at two levels: I) dynamics of macromolecular
complexes (e.g. their conformational change, or
their assembly and disassembly), and ii) the dynamics
of the interplay of macromolecular complexes
during their further assembly or disassembly
to form functional subcellular structures
(e.g. formation and transport of a pre-ribosomal
assembly through the nuclear pore, the formation
or disassembly of a coated membrane carrier, or
the formation and transport of a virus particle).
Biosynthetic transport is a cellular housekeeping
function of special interest with respect to medical
research, because many congenital diseases
are caused by defects in transport machinery
and biosynthetic transport is exploited at various
steps by pathogenic viruses for productive infection
and synthesis of viral progeny. Thus, our SFB
brings together research groups using structural,
cell biological, biochemical, molecular biological
and virological methods and analysing various
model organisms, from bacteria via yeasts to
mammalian cells. Our collaborative approach
allows integration of colleagues coming from different
fields in the life sciences, driven by their
common research interest. As a result, exchange
between the groups of a wide range of knowledge
and methodology is achieved naturally, and this,
combined with the common interest, fosters creativity
and at the same time strengthens a competent
and critical view to evaluate results.
Funding
49