Programmed cell death (PCD) occurs primarily through an evolutionary conserved form of cell suicide, termed apoptosis. 
Apoptosis is normally required for the elimination of cells produced in excess as well as potentially harmful cells that 
have sustained genetic damage. Many cells undergo apoptosis during development. The trophic theory of cell survival was 
originally developed to explain the massive neuronal cell loss in the developing vertebrate CNS and was later extended to 
include most, if not all, animal cells. This concept is based on the assumption that a cell-intrinsic suicide program 
operates by default unless it is suppressed by trophic factors such as the neurotrophins secreted by neighboring cells. This 
social control of cell survival ensures the functional integrity of a given tissue or organ by matching the number of 
different cell types to each other. However, inappropriate activation or inactivation of apoptosis is associated with a 
variety of human diseases including neurodegenerative disorders, stroke, AIDS, autoimmune diseases and cancer. 


The overall objective of my research is to gain a comprehensive understanding of the biological principles that 
underlie the regulation of apoptosis in the context of a multicellular organism, to identify and characterize the genes 
involved in this process, and to develop methods to influence them. Knowledge obtained in these studies provides new 
insights into diseases that are associated with altered rates of apoptosis.

I am utilizing the highly accessible genetic model system Drosophila melanogaster. In Drosophila, a large number of 
cells die during development. Like in vertebrates, this cell death is not genetically predetermined in a lineage-restricted 
manner, but is dependent on environmental circumstances. This appears to be a common strategy for the generation of complex 
patterns such as neuronal connectivity, and must be imposed on populations of cells whose numbers cannot be precisely 
specified by the genome. Thus, Drosophila shares the developmental plasticity with vertebrates. Therefore, 
molecular genetic studies in Drosophila promise considerable hope for advancing our understanding of the basic control 
mechanisms involved in the regulation of PCD in vertebrates including humans. 

Three novel cell death genes have been isolated in Drosophila: hid (head involution defective), reaper and grim. These genes 
induce apoptosis by activating a specialized class of death proteases, termed caspases. They do this by directly 
inhibiting IAPs (Inhibitor of Apoptosis Proteins), a highly conserved class of proteins, that inhibit caspases from 
activation.

The cell death inducer hid fulfils a number of requirements for the trophic theory of cell survival. Its expression is not 
only observed in dying cells but also in cells that live. However, ectopic expression of hid can very efficiently induce 
apoptosis. Thus, in surviving hid-expressing cells, very potent post-translational mechanisms must operate to prevent 
them from undergoing HID-induced apoptosis. Since the survival of most cells requires active suppression of the intrinsic 
cell suicide program according to the trophic theory, hid might provide a link between the cell death machinery and the 
mechanisms leading to its inactivation. 

My Short Term Research Goals is to understand the mechanism of regulation of hid activity by trophic (survival) pathways 
using a combination of genetic, molecular and biochemical approaches in the context of a developing multicellular organism. 

I showed genetically that activation of the RAS pathway leads specifically to inhibition of hid-induced apoptosis whereas 
reaper- and grim-induced apoptosis are not affected (Bergmann et al., 1998). This finding is interesting with regard to the 
trophic theory of cell survival, since hid expression is also observed in many cells that do not die suggesting that these 
cells require active signaling in order to survive. The anti-apoptotic function of RAS appears to provide this 
activity. RAS controls a number of effector pathways, two of which result in activation of protein kinases known to mediate 
its anti-apoptotic effect: the mitogen-activated protein kinase p42/44 (MAPK) and the Akt-kinase. I showed that the 
five MAPK phosphorylation sites in HID are critical for the survival-promoting activity of RAS (Bergmann et al., 1998), 
whereas activation of Akt-kinase is not required for regulation of hid activity (unpublished). Trophic survival 
signaling appears to be used in certain cellular paradigms. During embryogenesis, a subset of glia cells, the midline 
glia, enables correct migration and guiding of commissural axons in the CNS. I showed that the survival of the midline 
glia is dependent on inhibition of HID by activated MAPK. Moreover, the trophic signal for midline glia survival appears 
to be generated by the neighboring commissural axons such that only those midline glia cells that are appropriately 
positioned relative to the axons survive (Bergmann and Steller, submitted). 

1996 - 2000: 
Post-doctoral work in the laboratory of Prof. Dr. Hermann Steller at MIT on the role of survival 
signaling in Programmed Cell Death (Apoptosis)

1992-1996: 
Ph.D. in Biology in the laboratory of Prof. Dr. Christiane Nüsslein-Volhard
Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany

February 1992:	
Diploma in Biochemistry, University of Tübingen, Germany

1991: 
Diploma Thesis in the laboratory of Prof. Dr. Christiane Nüsslein-Volhard

1985-1990: 		
Studies in Biochemistry at the University of Tübingen, Germany