Yvonne Schmitz

Current Projects

Integrative development of modeling and simulation methods for regenerative systems (dIEM oSIRIS)

The ability of regeneration characterizes cell biological systems and is increasingly required for computer science systems as well. The Graduate School "dIEM oSiRiS" is a DFG-funded research training group. It brings together researchers from Medicine, Biology and Computer Science and contributes towards achieving new insights into the functioning of biological cell systems, establishing modelling and simulation as an experimental methodology in Biology, and developing innovative modelling and simulation methods and tools from which the understanding and the design of regenerative systems in general will benefit.

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Mathematical modeling of Neurodegenerative Processes in Alzheimer’s Disease (MSBN)

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid plaques in the brain of affected individuals. This project aims at modelling of neurodegenerative processes in AD. Our study focuses on the interactome of neuronal factors central to the proteolytic processing of amyloid precursor protein (APP) into Aβ, the main constituent of senile plaques. Factors considered in this model include proteases, trafficking adaptors, as well as a novel sorting receptor SORLA.

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Research Interest

Nucleo-cytoplasmic antagonist shuttling
"I am interested in Wnt signalling and its role in differentiation, where I am focussing on the role of nucleo-cytoplasmic antagonist shuttling."

The Wnt signalling pathway plays a significant role in the differentiation of neuronal stem cells. The protein β-catenin is the main protagonist and transcriptional co-factor of the pathway. However, not only β-catenin, also its antagonists have been proven to shuttle between cytoplasm and nucleus, while the functional relevance of this is still controversial.
How is the output of the pathway influenced by antagonist shuttling? Can Wnt signalling benefit from antagonist shuttling?
We formulated different hypotheses in order to examine the relevance of nucleo-cytoplasmic antagonist shuttling using mathematical modelling. We have investigated different shuttling mechanism (diffusive and facilitated transport) and considered retention of β-catenin by the antagonists as a possible function.
We found that Wnt signalling can benefit from nucleo-cytoplasmic shuttling of β-catenin antagonists. The analysis of the models shows that the breakdown of β-catenin cytoplasmic retention induced by APC shuttling can maximize the output of the pathway. Our study indicates that one protein may have two opposing functions within the same pathway depending on the cellular context. Furthermore, we showed that saturated protein translocation can under certain conditions be modelled by pure diffusion. A difference in the shuttling rate constants of sufficient orders of magnitude leads to an accumulation in either  compartment, which corresponds to saturation in translocation.

Academic Background

2009
Internship at the Sethna Group,
Cornell University, Ithaca/USA
2007 - present
PhD-Student at the SBI Team at the University of Rostock,
Rostock/Germany
2007
Dipl. Phys. (comparable to a Masters degree in physics)
Theoretical Physics/Complex Systems, ICBM
University of Oldenburg, Oldenburg/Germany
2002 - 2003
Courses in the masters program of the Department of Physics
University of Liverpool, Liverpool/United Kingdom
1999 - 2007
Student of Physics
University of Oldenburg, Oldenburg/Germany

Publications

Schmitz Y, Rateitschak K, Wolkenhauer O

Analysing the impact of nucleo-cytoplasmic shuttling of beta-catenin and its antagonists APC, Axin and GSK3 on Wnt/beta-catenin signalling

submitted for publication

Bader BM, Schmitz Y, Kuznetsov SA, Weiss DG (2013)

Wnt/beta-catenin signaling in differentiating human neural progenitor cells is controlled by spatio-temporal changes of beta-catenin distribution

submitted for publication

Lao A, Schmidt V, Schmitz Y, Willnow T, Wolkenhauer O (2012)

Multi-compartmental modeling of SORLA's influence on amyloidogenic processing in Alzheimer's disease

BMC Systems Biology 6:74
access

Schmidt V, Baum K, Lao A, Rateitschak K, Schmitz Y, Teichmann A, Wiesner B, Petersen CM, Nykjaer A, Wolf J, Wolkenhauer O, Willnow T (2012)

Quantitative modeling of amyloidogenic processing and its influence by SORLA in Alzheimer's disease

EMBO Journal 31: 187-200

 access

Schmitz Y, Wolkenhauer O, Rateitschak K (2011)

Nucleo-cytoplasmic shuttling of APC can maximize beta-catenin/TCF concentration

Journal of Theoretical Biology 279: 132-142
access

Schmitz Y, Baurmann M, Engelen B, Feudel U (2007)

Pattern Formation of Competing Microorganisms in Sediments

Mathematical Modelling of Natural Phenomena 4: 74-104
access

Lao A, Schmidt V, Schmitz Y, Willnow T, Wolkenhauer O

Regulated Trafficking of APP by SORLA in Alzheimer’s Disease

Systems Medicine International Conference (SYSMED), Dublin (Ireland), 9 September - 13 September 2012

Lao A, Schmidt V, Schmitz Y, Willnow T, Wolkenhauer O

Multi-compartmental modeling of APP processing influenced by SORLA in Alzheimer’s disease

13th International Conference on Systems Biology (ICSB), Toronto (Canada), 19 August - 23 August 2012

Schmitz Y, Rateitschak K, Wolkenhauer O

Mathematical modelling of the Wnt pathway: the influence of nucleo-cytoplasmic shuttling of β-catenin and its antagonists APC, Axin and GSK3

12th International Conference on Systems Biology (ICSB), Heidelberg/Mannheim (Germany), 28 August - 1 September 2011

Lao A, Schmitz Y, Schmidt V, Rateitschak K, Wolf J, Willnow T, Wolkenhauer O

Mathematical Modeling of APP Processing influenced by SORLA in Alzheimer’s Disease

12th International Conference on Systems Biology (ICSB), Heidelberg/Mannheim (Germany), 28 August - 1 September 2011

Schmitz Y, Wolkenhauer O, Rateitschak K

Mathematical modelling of nucleo-cytoplasmic shuttling of beta-catenin and its antagonist APC

11th International Conference on Systems Biology (ICSB), Edinburgh (GB), 10-15 October 2010