Genetics of Apoptosis

number of clones to single genes per transfection. Because an individual transfection
is performed for every cDNA clone in a library, the process requires thousands of
transfections in parallel. Thus, it was only a logical step to use robotic systems in the
screen. Reporter assays to detect apoptosis and a transfection robot, especially tailored
to multiple simultaneous transfections, were also developed (Kachel and Grimm,
2002).

3.

Conclusions

Cell-culture studies with the correlative, the selection, and the screen approaches have
already led to the description of a number of genes involved in apoptosis. However,
most of them are still isolated entities, and such concise stories as derived from the
work with C. elegans (Chapter 10) cannot yet be told about the genes isolated in cell
culture. Clearly, additional efforts by the investigators are required to integrate these
apoptosis genes into a signaling network. However, some general statements can
already be deduced from the available data.
Interestingly, many inhibitors or mediators determined by the presented methods
can also function with stimuli other than the ones that were originally used for their
isolation. This argues for a very redundant signaling during apoptosis. Hence, we
must revise the notion of a linear pathway emanating from one stimulus and
progressing in a straight succession of sequentially activated apoptosis mediators down
to caspases. It is more likely that nature uses many, partially redundant signaling
pathways that feed back to further mediators of apoptosis. This cross-talk might
stabilize the system and prevent mistakes in the activation of this deadly program.
While many chapters in this book focus on several gene families involved in
apoptosis (such as the TNFR or the Bcl-2 family), these families are underrepresented
in our description of cell-culture systems in apoptosis. Rather than a shortcoming,
this could be an advantage, as the defined conditions of cell culture seem to allow
researchers to clone genes outside the standard apoptosis pathways. As every gene
from cell culture characterizes a signaling pathway, it is possible to use these genes to
describe these unique signals and the cellular processes they activate.
All in all, cell culture has already made valuable contributions to apoptosis research
and greatly deepened our understanding of cell death. With all the information gained
from this work, it is safe to say that cell-culture systems can be expected to keep many
researchers in the field of apoptosis busy for some time to come.

210 GENETICS OF APOPTOSIS