Team
Team

Silke Kleinbölting, Dr. rer. net.

Position: Senior Research Scientist

Room no.: CP-02-133

Telephone no.: +49 (0)231 755 8834

Email: silke.kleinboelting@tu-dortmund.de

Member of the group: 08/2019

University degree: Dr. rer. nat. in Biochemistry

 

Earlier positions:

2015-2019

Postdoctoral DFG research fellow, Stanford University, USA

Structural and functional investigation of the entry mechanism of measles virus.
Improvement of IgE:FcεRI disurptive antibody.

Principal Investigator: Prof. Dr. T. Jardetzky

2014-2015

Postdoctoral research fellow, University Bayreuth, Germany.

Characterization of activators and Inhibitors for the humane soluble adenylyl cyclase.

Principal Investigator: Prof. Dr. C. Steegborn

2010-2014

PhD student, University Bayreuth, Germany.

Fundamental activation mechanism by metal ions and bicarbonate as well as further development of inhibitors and activators for cyclases with the main focus on the humane soluble adenylyl cyclase (hsAC).

Principal Investigator: Prof. Dr. C. Steegborn

2009-2010

Internship, University of Auckland, New Zealand

Structural biology and drug design for proteins of the anthranilate synthase complex of M. tuberculosis.

Principal Investigator: Prof. Dr. T. Baker

2007-2009

Master of Science (M.Sc.) - Biochemistry

Ruhr-University Bochum - MPI Dortmund (Principal Investigator: Prof. Dr. A. Wittinghofer)

2004-2007

Bachelor of Science (B. Sc.) - Biochemistry

Ruhr-University Bochum - MPI Dortmund (Principal Investigator: Prof. Dr. A. Wittinghofer)

 

Expertise: X-ray crystallography, biophysics, assay development, expression and purification

Off-Lab activities (hobbies): Snowboarding, board games, travelling

Research projects:

Identification and characterization of selective inhibitors against the TET2 enzyme, which has an important role in epigenetic modification of physiological and pathological processes. Therefore, TET2 is a promising target to develop epigenetic modulators as new therapeutic agents.

Investigation of novel small molecules for FKBP12-target protein-protein interactions. FKBPs are playing a central role in modulating various signal pathways and are known for their critical function in oncogenic diseases

Publications:

Kleinboelting, S., Diaz, A., Moniot, S., van den Heuvel, J., Weyand, M., Levin, L. R., Buck, J., and Steegborn, C. (2014) Crystal structures of human soluble adenylyl cyclase reveal mechanisms of catalysis and of its activation through bicarbonate. Proc. Natl. Acad. Sci. 111, 3727–3732.

Kleinboelting, S., van den Heuvel, J., Kambach, C., Weyand, M., Leipelt, M., and Steegborn, C. (2014a). Expression, purification, crystallization and preliminary X-ray diffraction analysis of a mammalian type 10 adenylyl cyclase. Acta Crystallogr. Sect. F Struct. Biol. Commun. 70, 467–469.

Banerjee, A., Adolph, R. S., Gopalakrishnapai, J., Kleinboelting, S., Emmerich, C., Steegborn, C., and Visweswariah, S. S. (2015) A Universal Stress Protein (USP) in Mycobacteria Binds cAMP. J. Biol. Chem. 290, 12731–12743.

Kleinboelting, S., van den Heuvel, J., and Steegborn, C. (2014b). Structural analysis of human soluble adenylyl cyclase and crystal structures of its nucleotide complexes - implications for cyclase catalysis and evolution. FEBS J. 281, 4151–4164.

Bashiri, G., Johnston, J. M., Evans, G. L., Bulloch, E. M. M., Goldstone, D. C., Jirgis, E. N. M., Kleinboelting, S., Castell, A., Ramsay, R. J., Manos-Turvey, A., Payne, R. J., Lott, J. S., and Baker, E. N. (2015) Structure and inhibition of subunit I of the anthranilate synthase complex of Mycobacterium tuberculosis and expression of the active complex. Acta Crystallogr. D Biol. Crystallogr. 71, 2297–2308.

Kleinboelting, S., Ramos-Espiritu, L., Buck, H., Colis, L., Heuvel, J. van den, Glickman, J. F., Levin, L. R., Buck, J., and Steegborn, C. (2016) Bithionol Potently Inhibits Human Soluble Adenylyl Cyclase through Binding to the Allosteric Activator Site. J. Biol. Chem. 291, 9776–9784.

Ramos-Espiritu, L., Kleinboelting, S., Navarrete, F. A., Alvau, A., Visconti, P. E., Valsecchi, F., Starkov, A., Manfredi, G., Buck, H., Adura, C., Zippin, J. H., van den Heuvel, J., Glickman, J. F., Steegborn, C., Levin, L. R., and Buck, J. (2016) Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase. Nat. Chem. Biol. 12, 838–844.*

Gasser, P., Tarchevskaya, S., Guntern, P., Brigger, D., Zbaren, N., Kleinboelting, S., Heusser, C., Jardetzky, T., Eggel, A., (2019) The next generation anti-IgE antibody ligelizumab efficiently suppresses FcεRI-dependent allergic responses through neutralization of free IgE and inhibition of IgE production. Nat. Commun. Revision.

*basis for patent application (WO2017190050A1)