Dr. Yvonne Schmitz

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

PhD Students (from 2007-01-01 until 2014-12-31)

Thesis title: "Compartmental Modelling of the Wnt pathway"

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 - 2014

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

Selected publications

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

Schmitz Y, Rateitschak K, Wolkenhauer O (2013)

Cellular Signalling, 2210:2221

Spatio-temporal distribution changes and nucleo-cytoplasmic shuttling rates regulate differentiation in human neural progenitor cells

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

submitted for publication

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

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

BMC Systems Biology 6:74

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

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)

EMBO Journal 31: 187-200

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

Schmitz Y, Wolkenhauer O, Rateitschak K (2011)

Journal of Theoretical Biology 279: 132-142

Pattern Formation of Competing Microorganisms in Sediments

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

Mathematical Modelling of Natural Phenomena 4: 74-104
access

Regulated Trafficking of APP by SORLA in Alzheimers Disease

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

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

Venue: Dublin, Ireland

Multi-compartmental modeling of APP processing influenced by SORLA in Alzheimers disease

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

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

Venue: Toronto, Canada

Mathematical Modeling of APP Processing influenced by SORLA in Alzheimers Disease

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

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

Venue: Heidelberg/Mannheim, Germany

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

Schmitz Y, Rateitschak K, Wolkenhauer O

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

Venue: Heidelberg/Mannheim, Germany

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

Schmitz Y, Wolkenhauer O, Rateitschak K

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

Venue: Edinburgh, UK

Elucidating the role of nucleo-cytoplasmic shuttling of beta-catenin antagonists by mathematical modelling

Schmitz Y, Bader BM, Weiss DG, Wolkenhauer O, Rateitschak K

Summer School on Systems Biology for Medical Applications, Tenerife, Spain, 30.09.-02.10.2008

Venue: Tenerife, Spain

Quantitative 3D image analysis to study the beta-catenin translocation during differentiation of human neural progenitor cells

Bader BM, Schmitz Y, Redlich B, Rateitschak K, Wolkenhauer O, Weiss DG

2nd International Congress on Stem Cells and Tissue Formation, Dresden, Germany, July 2008

Venue: Dresden, Germany

Mathematical modeling of neurodegenerative processes in alzheimer's diesease

Rateitschak K, Schmidt V, Carlo AS, Sporbertm A, Lao A, Wolkenhauer O, Willnow T

First status seminar of the Helmholtz alliance on systems biology. Potsdam, Germany, June 2008

Venue: Potsdam, Germany

Compartmental Modelling of the Wnt pathway

Schmitz Y

2014