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Prof. Dr. rer. nat. Marius Ueffing
Group Head, Institute Director
Email: marius [dot] ueffing [at] uni-tuebingen [dot] de
Dr. rer. nat. Karsten Boldt
Email: karsten [dot] boldt [at] uni-tuebingen [dot] de
Medical Proteome Center
Centre for Ophthalmology
Institute for Ophthalmic Research
Our main interest is on how genetic gene variants are transferred into function and how function is systemically perturbed upon disease. The goal is to study mechanisms of disease first and then to establish a basis for the development of rational strategies for therapy and prevention. Towards this goal, we rather look at protein networks than single genes or proteins and analyze their integration into a systemic physiological context. Physiology and pathophysiology can then be studied in a comparative, systematic, analytical fashion. The goal here is to learn, which critical functions on the molecular level are perturbed in neurodegenerative processes.
To this end we apply mainly state of the art mass spectrometry (MS) based analytical strategies, including quantitative methods like SILAC or ICPL.
During the last years our main efforts focused on the development of combinatory approaches to use the potential of quantitative MS for the analysis of protein complexes, protein networks and the impact of gene variants on those.
We further use quantitative MS to decipher the impact of mutations or noxes on the proteomic level. In combination with the detection and the dynamics of post-translational modifications, this enables us to further understand the cellular processes underlying disease.
As a core unit we offer our knowledge and the power of MS, including quantitative MS to the medical campus at the University Clinics in TÃ¼bingen.
Boldt K*,Mans DA*, Won J*, van Reeuwijk J, Vogt A, Kinkl N, Letteboer SJF, Hicks WL,
Hurt RE, Naggert JK, Texier Y, den Hollander AI, Koenekoop RK, Bennett J, Cremers FP,
Gloeckner CJ, Nishina PM, Roepman R, Ueffing M. Disruption of intraflagellar protein
transport in photoreceptor cilia causes Leber congenital amaurosis in humans and mice.
J Clin Invest. 2011 Jun 1; 121(6):2169-80.
Bengel D*, Boldt K*, Davis EE, Burtscher I, TrÃ¼mbach D, Diplas B, AttiÃ©-Bitach T, Wurst W,
Katsanis N, Ueffing M,Lickert H. Pitchfork regulates cilia disassembly and left-right
asymmetry. Dev Cell. 2010 Jul 20;19(1):66-77.
den Hollander AI*, Koenekoop RK*, Mohamed MD*, Arts HH*, Boldt K, Towns KV,
Sedmak T, Beer M, Nagel-Wolfrum K, McKibbin M, Dharmaraj S, Lopez I, Ivings L,
Williams GA, Springell K, Woods CG, Jafri H, Rashid Y, Strom TM, van der Zwaag
B, Gosens I, Kersten FF, van Wijk E, Veltman JA, Zonneveld MN, van Beersum SE,
Maumenee IH, Wolfrum U, Cheetham ME, Ueffing M, Cremers FP*, Inglehearn CF*,
Roepman R*. Mutations in LCA5, encoding the ciliary protein lebercilin, cause
Leber congenital amaurosis. Nature Genetetics. 2007;39(7):889-95.
Gloeckner CJ, Boldt K, Schumacher A, Roepman R, Ueffing M. A novel tandem affinity
purification strategy for the efficient isolation and characterisation of native protein
complexes. Proteomics. 2007;7(23):4228-34.
Meixner A, Boldt K, Van Troys M, Askenazi M, Gloeckner CJ, Bauer M, Marto JA, Ampe C,
Kinkl N, Ueffing M. A QUICK screen for Lrrk2 interaction partners - leucine-rich repeat kinase 2
is involved in actin cytoskeleton dynamics. Mol Cell Proteomics. 2011 Jan;10(1):M110.001172.
Gloeckner CJ, Boldt K, von Zweydorf F, Helm S, Wiesent L, Sarioglu H, Ueffing M.
Phosphopeptide analysis reveals two discrete clusters of phosphorylation in the N-terminus
and the Roc domain of the Parkinson-disease associated protein kinase LRRK2.
Journal of Proteome Research. 2010 Apr 5;9(4):1738-45.
* these authors contributed equally