Ruprecht-Karls-Universitšt Heidelberg





Spokesperson:
Prof. Bernd Bukau

ZMBH, Im Neuenheimer Feld 282
69120 Heidelberg, Germany
Tel.: + 49-6221 54 6795
Fax.: +49-6221 54 5894
bukau@zmbh.uni-heidelberg.de


SFB 1036 managing office /
SFB 1036 - Geschäftsstelle

Veronika Helm
ZMBH, Im Neuenheimer Feld 282
69120 Heidelberg, Germany
Tel.: + 49-6221 54 8102
email: v.helm@zmbh.uni-heidelberg.de



Welcome to the SFB 1036


CELLULAR SURVEILLANCE AND DAMAGE RESPONSE





As a consequence of the intrinsic biochemical fragility of molecules and limited robustness and precision of cellular processes, cells must routinely deal with faulty or damaged molecules and perturbations of cell physiology. Damage and erroneous processes may be tolerable or even result in some advantage eventually contributing to evolutionary diversification, but may otherwise have catastrophic consequences. Some types of damage can become encoded in the genome, and manifest as inherited or acquired diseases. Others may perturb cellular homeostasis and result in malfunction, degeneration and ageing of cells and organisms. Damage and errors are aggravated by a multitude of internal and environmental insults (stresses). Consequently, all cells, from bacteria to human, have developed a powerful network of systems, acting at multiple levels on macromolecules, cellular compartments, whole cells and entire organs, to minimize and reverse the damage that would ensue if mistakes and abnormal molecules went by unmonitored and uncorrected. The medical dimension of surveillance and damage response pathways becomes apparent when these pathways lose effective function, since this usually results in disease.

The long-term goal of this Collaborative Research Center (Sonderforschungsbereich, SFB) entitled "Cellular surveillance and damage control" is to elucidate the molecular mechanisms driving and coordinating damage control systems. In 17 research projects (TP) and 2 service projects (Z) the question of how the quality of gene function is monitored and how damage signals are integrated to elicit appropriate responses will be analyzed. This should provide a comprehensive understanding of how cells react to damage and establish and maintain homeostasis. Towards this goal the SFB will investigate:

Safeguarding systems that avert potential errors and damage by ensuring proper performance of cellular processes such as DNA replication, translation, and those underpinning homeostatic environments (e.g. iron homeostasis or redox state).

Damage repair systems which detect damaged or abnormal macromolecules (DNA, RNA, proteins) and provide repair and/or regulated elimination.

Stress response pathways that increase cellular capacity to cope with specific or global stress (e.g. heat shock, oxidative stress, protein overload in the endoplasmic reticulum). With the planned research on surveillance mechanisms and damage responses we are aiming at providing a comprehensive understanding of how cells react to damage and establish and maintain homeostasis.



News

The SFB 1036 funding has been renewed for the next four years (German press release)

Dr. Cindy Voisine's Fulbright fellowship (from October to December 2016) is supported by the SFB 1036.
Dr. Voisine is a visiting scientist from the Northeastern Illinios University.



Events
Sept. 22, 2016
4 p.m.

Jeffrey Brodsky (University of Pittsburgh, Department of Biological Sciences, Pittsburgh, USA)
ER associated degradation and protein conformational disease: Lessons from model systems and therapeutic opportunities
ZMBH seminar room 001 | INF 282 (pdf)


Photographs of Events

photos from the kick-off meeting 2013 photos from the PhD and PostDoc retreat 2013
photos from the SFB 1036 retreat at Flehingen Castle, 2014 Impressions of the SFB Congress in November 2014
End of year party 2014 & Bernd Bukau´s 60th birthday group photo of the SFB members at retreat in Bad Wimpfen, 2015
End of year party 2015 & inauguration seminars by
Claudio Joazeiro and H. Kaessmann


Recent publications

Wunderle, L., Knopf, J.D., Kühnle, N., Morle, A., Hehn, B., Adrain, C., Strisovsky, K., Freeman, M., Lemberg, M.K. (2016) Rhomboid intramembrane protease RHBDL4 triggers ER-export and non-canonical secretion of membrane-anchored TGF-alpha. Sci. Rep. 6:27342; doi: 10.1038/srep27342 (Abstract).

Nillegoda, N.B., Kirstein, J., Szlachcic, A., Berynskyy, M., Stank, A., Stengel, F., Arnsburg, K., Gao, X., Scior, A., Aebersold, R., Guilbride, D.L., Wade, R.C., Morimoto, R.I., Mayer, M.P., Bukau, B. (2015) Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation. Nature 524:247-251; doi:10.1038/nature14884 (read more).

Walter, D., Lier, A., Geiselhart, A., Thalheimer, F.B., Huntscha, S., Sobotta, M.C., Moehrle, B., Brocks, D., Bayindir, I., Kaschutnig, P., Muedder, K., Klein, C., Jauch, A., Schroeder, T., Geiger, H., Dick, T.P., Holland-Letz, T., Schmezer, P., Lane, S.W., Rieger, M.A., Essers, M.A., Williams, D.A., Trumpp, A., Milsom, M.D. (2015) Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells. Nature 520:549-552; doi: 10.1038/nature14131. (Abstract).

Miller, S.B.M., Ho, C.-T., Winkler, J., Khokhrina, M., Neuner, A., Mohamed, M.Y.H. et al. (2015). Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition. EMBO J 34:778-797 (Abstract).

Miller, S.B.M., Mogk, A., Bukau, B. (2015). Spatially organized aggregation of misfolded proteins as cellular stress defense strategy. J Mol Biol 427:1564-1574 (Abstract).

Peralta, D., Bronowska, A.K., Morgan, B., Doka, E., Van Laer, K., Nagy, P., Gräter, F., Dick, T.P. (2015). A proton relay enhances H2O2 sensitivity of GAPDH to facilitate metabolic adaptation. Nat Chem Biol 11:156-163. (Abstract).

Sobotta, M.C., Liou, W., Stocker, S., Talwar, D., Oehler, M., Ruppert, T., Scharf, A.N., Dick, T.P. (2015) Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling. Nat Chem Biol 11:64-70. (Abstract).

Abu-Odeh, M., Salah, Z., Herbel, C., Hofmann, T.G., Aqeilan, R.I. WWOX, the common fragile site FRA16D gene product, regulates ATM activation and the DNA damage response. Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):E4716-25. doi: 10.1073/pnas.1409252111. Epub 2014 Oct 20. (Abstract).

Khmelinskii, A., Blaszczak, E, Pantazopoulou M, Fischer B, Omnus DJ, Le Dez G, Brossard A, Gunnarsson A, Barry JD, Meurer M, Kirrmaier D., Boone, C., Huber, W., Rabut, G., Ljungdahl, P.O., Knop, M. (2014). Protein quality control at the inner nuclear membrane. Nature. 2014 Dec 18;516(7531):410-3. doi: 10.1038/nature14096. (Abstract).






















































The SFB 1036 is funded by the