First and foremost, I would like to express my deepest gratitude to Dr. Mary Horne for giving me the opportunity to complete my PhD here in the US. This dissertation would not have been possible without her constant support and guidance.
I also very much appreciate the trust she has placed in me over the past years.
I would like to thank Dr. Gabriele Fischer von Mollard for reviewing this unconventional thesis and her support during this very interesting time. Her willingness to support an external PhD made this project possible.
In addition I would like to thank Dr. Johannes Hell for the support I received during my time in Iowa and Davis.
I also want to thank the Faculty of Chemistry in Bielefeld and the Departments of Pharmacology in Iowa and Davis.
Special thanks go to my co-workers, Michaela, Nicole and Eric, who helped me with all the little and big things, in the lab and everywhere else. In particular I want to thank Michaela for all the hard work and long ours she invested in my project. I really enjoyed spending time with you guys (in the lab and outside).
I also thank the members from Hell for their open arms, helpful discussions and introduction into the special characteristics of Midwestern lifestyle. Thank you very much Duane, Rob, Jason, Amy, Uche, Cheston, Hui, Cigdem, Lucas, Tom, I had a great time. I hope we will meet again.
Thank you Ivar, you know why. Ohne dich wäre ich nie auf die Idee gekommen Deutschland zu verlassen und mich in ein so großes Abenteuer zu stürzen. Danke dass du so bist wie du bist.
Nicht zuletzt möchte ich meiner Familie danken. Auch wenn ich euch nicht sehr oft sehen konnte, habe ich doch jeden Sonntag auf Neuigkeiten gewartet. Die vielen kleinen und großen “Kehrpakete” haben mir so manchen Abschnitt versüßt und das Weitermachen erleichtert.
121
Erklärung
Die vorliegende Arbeit wurde unter der wissenschaftlichen Anleitung von Prof. Dr.
Mary Horne an der Fakultät für Pharmacology der Universität von Iowa, Iowa City, USA und der Fakultät für Pharmacology der Universität von Kalifornien, Davis, USA angefertigt.
Hiermit versichere ich, dass ich die vorliegende Dissertation ohne fremde Hilfe selbständig verfasst und nur die angegebenen Quellen und Hilfsmittel benutzt habe.
Wörtlich oder dem Sinn nach aus Werken entnommene Stellen sind unter Angabe der Quellen kenntlich gemacht. Ich habe bisher an keiner anderen Fakultät oder Hochschule einen Antrag auf Zulassung zur Promotion eingereicht und die vorliegende Dissertation weder in der gegenwärtigen noch in einer anderen Fassung vorgelegt.
Maike Zimmermann
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Curriculum Vitae
Maike Zimmermann Education
PhD (Dr. rer. nat.) Biochemistry, University of California, Davis, USA and University of Bielefeld, Germany, 2012, Dissertation: Contribution of cyclin G2 to the cell cycle inhibitory effects of cancer therapeutics, Advisor: Prof. Dr. Mary Horne
Diplom Biochemistry, University of Bielefeld, Department of Chemistry and Department of Biology, Bielefeld, Germany, 2007, Thesis: Characterization of the hybrid histidine kinase Slr1759 of the cyanobacterium Synechocystis sp. PCC 6803, Advisor: Prof. Dr. Dorothee Staiger
Research Experience
09/09-present Visiting Scholar/Assistant Specialist, The University of California, Davis, School of Medicine, Department of Pharmacology, Davis, California, USA (Dr. Mary Horne lab)
11/07-08/09 Visiting Scholar/Research Assistant III, The University of Iowa College of Medicine, Department of Pharmacology, Iowa City, Iowa, USA (Dr.
Mary Horne lab)
05/05-06/05 Advance practical training, University of Bielefeld, Department of Chemistry, Bielefeld, Germany (Dr. Frey lab)
10/01-04/07 Studies of Biochemistry, University of Bielefeld, Department of Chemistry, Bielefeld, Germany
Teaching Experience
10/06-12/06 Preparation and mentoring of undergraduate students during the Basic biology practical course I, University of Bielefeld, Department of Biology, Bielefeld, Germany
10/05-12/05 Preparation and mentoring of undergraduate students during the Immunology practical course, University of Bielefeld, Department of Chemistry, Bielefeld, Germany
Honors and Awards
07/25/11-07/29/11 Trainee scholarship for the Flow Cytometry Intensive Course sponsored by Tree Star
123 Publications
1. Michel, K.P., Schroder, A.K., Zimmermann, M., Brandt, S., Pistorius, E.K., Frankenberg-Dinkel, N., and Staiger, D. (2009). The hybrid histidine kinase Slr1759 of the cyanobacterium Synechocystis sp. PCC 6803 contains FAD at its PAS domain.
Archives of microbiology 191, 553-559.
2. Zhou, J., Su, P., Wang, L., Chen, J., Zimmermann, M., Genbacev, O., Afonja, O., Horne, M.C., Tanaka, T., Duan, E., et al. (2009). mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America 106, 7840-7845.
3. Xu, H., Ginsburg, K.S., Hall, D.D., Zimmermann, M., Stein, I.S., Zhang, M., Tandan, S., Hill, J.A., Horne, M.C., Bers, D., et al. (2010). Targeting of protein phosphatases PP2A and PP2B to the C-terminus of the L-type calcium channel Ca v1.2. In Biochemistry, pp. 10298-10307.
4. Zimmermann, M., Arachchige Don, A.S., Donaldson, M.S., Dallapiazza, R.F., Cowan, C.E., and Horne, M.C. (2012). Elevated Cyclin G2 expression intersects with DNA damage checkpoint signaling and is required for a potent G2/M checkpoint arrest response to doxorubicin. Journal of Biological Chemistry.
Abstracts
1. Arachchige Don, A.S., Zimmermann, M., Cowan, C., Dallapiazza, R., Duven, J., Wong, M. and *Horne, M.C. Cyclin G2 intersects with the ATM-Chk2 dsDNA-damage response pathway and contributes to doxorubicin-induced G2/M checkpoint arrest. Midwest Breast Cancer Research Symposium, Iowa City, 2009.
2. Arachchige Don, A.S., *Zimmermann, M., Cowan, C., Le, X.F., Mou, E. and Horne, M.C. Modulation of cyclin G2 expression and localization in tumor cells responding to inhibitors of the PI3K/AKT/mTOR pathway. Midwest Breast Cancer Research Symposium, Iowa City, 2009.
3. *Zimmermann, M., Arachchige Don, A.S., Cowan, C., Mou, E. and Horne, M.C.
Binding partners and post-translational regulation of the unconventional, estrogen repressed-cell cycle inhibitor, cyclin G2. Midwest Breast Cancer Research Symposium, Iowa City, 2009.
4. *Zimmermann, M., Cowen, C. and Horne, M.C. The FOXO regulated cell cycle inhibitor Cyclin G2 is upregulated by mTOR inhibitor Rapamycin and opposed by the Skp2 associated ubiquitin Ligase. American Society for Cell Biology meeting, San Diego, 2009.
5. Zimmermann, M., Arachchige Don, A.S., Mou, E., and *Horne, M.C. Modulation of expression and localization of cyclin G2, an estrogen- and HER2 repressed cell cycle inhibitor. American Society for Cell Biology, San Diego, 2009.
6. Arachchige Don, A.S., *Zimmermann, M., Dallapiazza, R., Donaldson, M., Cowan, C., and Horne, M.C. Cyclin G2 intersects with the ATM-Chk2 dsDNA-damage response pathway and contributes to doxorubicin-induced G2/M checkpoint