Prof. Dr. Ernst Hafen

 

Main Goals, Keywords

The goal of our research is to understand how cells communicate and how with each other and how these cellular interactions reproducibly mediate the plethora of decisions that cells make during development.

Keywords: genetics, signal transduction, Drosophila, insulin signaling, nutrition, cell size, growth

Group Members

2 senior research fellow, 3 postdoctoral fellows, 9 PhD students, 3 technicians (1 trainee), 1 secretary

Previous and Current Research

We want to unravel the genetic circuitry of cellular processes during development. To this end we use the powerful genetic tools available in Drosophila. We have shown that the specification of R7 photoreceptor cells fate depends on the Sevenless receptor tyrosine kinase and the Ras/MAP Kinase. Dorsal closure, a process of epithelial joining in the Drosophila embryo resembling wound healing, is controlled by the coordinate activation of the DPP/TGFß and JNK pathway. More recently we turned our interest to the question of how cell, organ, and body size is genetically controlled. By performing large scale genetic genetic screens we were able to saturate the genome for mutations that affect the size of cells, organs, and the entire organism but that do not interfere with cellular differentiation. In the Drosophila genome, we identified a total of approximately 30 genes that promote growth and 25 genes that inhibit growth. Many of these genes encode proteins constituting the Insulin/TOR signaling pathway. The activity of this pathway controls cellular and organismal growth in response to the availability of nutrients. Mutations that reduce insulin signaling promote longevity confirming the universal link between insulin signaling, caloric restriction and lifespan first discovered in nematodes.

Future Projects

The genetic screen for growth mutants has provided us with a large number of genes. Many of our present projects focus on the characterization of these genes and the corresponding proteins to understand how they control cell and body size. The quest for unreaveling the metabolic networks involved in growth control is facilitated by our new affiliation with the Institute of Molecular Systems Biology. In a collaborative effort with the group of Ruedi Aebersold we are purifying and analyzing the protein complexes associated with our 55 gene products involved in growth regulations.

Techniques and Equipment

We use the advanced genetic tools available in Drosophila and combine them with cell biological and biochemical methods in cell culture.

Selected Publications

• Montagne, J., Lecerf, C., Parvy, J.P., Bennion, J.M., Radimerski, T., Ruhf, M.L., Zilbermann, F., Vouilloz, N., Stocker, H., Hafen, E., Kozma SC, Thomas G. PLoS Genet. The nuclear receptor DHR3 modulates dS6 kinase-dependent growth in Drosophila. May 6;6:e1000937 (2010).
• Aegerter-Wilmsen, T., Smith, A.C., Christen, A.J., Aegerter, C.M., Hafen, E., Basler K. Exploring the effects of mechanical feedback on epithelial topology. Development. Feb;137(3):499-506 (2010).
• Köhler, K., Brunner, E., Guan, X.L., Boucke, K., Greber, U.F., Mohanty, S., Barth, J.M., Wenk, M.R., Hafen, E.  A combined proteomic and genetic analysis identifies a role for the lipid desaturase Desat1 in starvation-induced autophagy in Drosophila. Autophagy. Oct; 5(7): 980-90 (2009). Epub 2009 Oct 22.

Funding

Grants from SNF, EU Research Training Networks, Oncosuisse, Roche Research Fellow

URL

www.imsb.biol.ethz.ch

www.imsb.ethz.ch/researchgroup/hafene