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logo" style="width:278px; height:75px ; clear:left; margin-left:0px; margin-top:0px"><br><br> </div> <div id="math">MATHEMATICS OF SELF-ORGANISATION IN CELL SYSTEMS</div> <div id="underlogo"></div> <div id="left"> <div id="separatemenu">&nbsp;</div> <div id="betweenmenu">&nbsp;</div> <div id="undermenu">&nbsp;</div> <div id="placemenu"> <div class="menu"> <ul> <li><a href="http://www.biostruct.uni-hd.de/index.php" class= "current" >Home</a></li> <!-- <li><a href="http://www.biostruct.uni-hd.de/folder_research/research.php" >Research</a></li> --> <li><a href="http://www.biostruct.uni-hd.de/folder_people/people.php" >People</a></li> <li><a href="http://www.biostruct.uni-hd.de/folder_publications/publications.php" >Publications</a></li> <li><a href="http://www.biostruct.uni-hd.de/folder_theses/theses.php" >Completed Theses</a></li> <li><a href="http://www.biostruct.uni-hd.de/folder_funding/funding.php" >Projects and Funding</a></li> <li><a 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href="http://euro-math-soc.eu/year-mathematical-biology-2018">Year of Mathematical<br> Biology 2018</a></li> <li><a href="http://www.bioquant.uni-heidelberg.de">BioQuant</a></li> <li><a href="http://www.bioms.de">BIOMS</a></li> <!-- <li><a href="http://www.haw.uni-heidelberg.de/forschung/win-kolleg.de.html">WIN-Kolleg</a></li> --> <!--<li><a href="http://www.iwr.uni-heidelberg.de/organization/gk">Graduated College at IWR</a></li>--> <li><a href="http://www.esmtb.org">ESMTB</a></li> <!-- <li><a href="http://mmns.mimuw.edu.pl">MMNS</a></li> --> <!--<li><a href="http://www.biostruct.uni-hd.de/MapMathBioEu.php" >A Map of Mathematical Biology in Europe</a></li>--> </ul> </div> </div> <div id="pict5"> <div class="contact"> <ul> <li><b>Contact:</b><br>Prof. Dr.<br> Anna Marciniak-Czochra</li> <li><a href="mailto:Anna.Marciniak@iwr.uni-heidelberg.de">anna.marciniak@iwr.uni-heidelberg.de</a> </li> <li>+49 (0)6221 5414140</li> </ul> </div> </div> <div id="impressum"> <a href="http://www.iwr.uni-heidelberg.de/impressum/">impressum</a> </div> <div> </body> </html> <div id="main"> <div id="pict1"><a class="clearcss" id="single_image1" href="images/page_pictures_nov18/12L.png" title="concentration of free growth factors in a spatially distributed model of cancer growth for large diffusion (2D domain)"><img src="images/page_pictures_nov18/12.png" alt="by Steffen H&#228;rting"></a></div> <div id="pict2"><a class="clearcss" id="single_image2" href="images/page_pictures_nov18/11L.png" title="finite element simulation of tissue deformation due to external forces"><img src="images/page_pictures_nov18/11.png" alt="by Moritz Mercker"></a></div> <div id="pict3"><a class="clearcss" id="single_image3" href="images/page_pictures_nov18/10L.png" title="finite element simulation of budding processes in biological membranes"><img src="images/page_pictures_nov18/10.png" alt="by Moritz Mercker"></a></div> <div id="pict4"><a class="clearcss" id="single_image4" href="images/page_pictures_nov18/9L.png" title="concentration of precancerous cells"><img src="images/page_pictures_nov18/9.png" alt="by Steffen H&#228;rting"></a></div> <div id="section">Welcome to</div> <div id="content"> <div id="pict6"><a class="clearcss" id="single_image5" href="images/6L.png" title="concentration of precancerous cells in a spatially distributed model of cancer growth for large diffusion (2D domain)"><img src="images/6.png" alt="by Steffen H&#228;rting"></a></div> <div id="pict7"><a class="clearcss" id="single_image6" href="images/7L.png" title="concentration of precancerous cells in a spatially distributed model of cancer growth for small diffusion (2D domain)"><img src="images/7.png" alt="by Steffen H&#228;rting"></a></div> <div id="pict8"><a class="clearcss" id="single_image7" href="images/8L.png" title="an irregular solution of a receptor-based model with hysteresis"><img src="images/8.png" alt="by Alexandra K&#246;the"></a></div> <h2>Research Group</h2> <h2>Applied Analysis and Modelling in Biosciences</h2> <h2><a href="http://www.marciniak-czochra.uni-hd.de">Prof. Dr. Anna Marciniak-Czochra</a></h2> <h3>Institute of Mathematics, <br> Interdisciplinary Center of Scientific Computing (IWR) <br> and BIOQUANT Center, Heidelberg University.</h3> <br> <br> <table class="table2"> <tr><td> <!--The group is focused on multi-scale mathematical modelling and analysis of the dynamics of structure formation and self-organisation in cell systems. Our interests lie in the interface between mathematics and biosciences. Field of focus is the dynamics of self-organisation and structure formation in developmental and regeneration processes, and cancer. Our current research is devoted to the following biological applications: </td></tr> </table> <br> <div class="site"> <ul> <li>signalling and transport processes in cancerogenesis</li> <li>pattern formation and regeneration in developmental systems</li> <li>self-renewal and differentiation of stem cells during hematopoiesis and neurogenesis</li> </ul> --> <b>Research focus:</b> The interdisciplinary expertise of our research group lies in the areas of applied mathematics and mathematical and computational biosciences. Specifically, our field of focus is the dynamics of self-organisation and structure formation in developmental and regeneration processes and in cancer. The aim of our research is to develop and analyse mathematical models of the dynamics of structure formation in multicellular systems and to develop new mathematical methods of modelling of such complex processes. We collaborate closely with experimentalists and clinicians, and pursue mathematical problems arising in modelling of biological processes, both analytically and computationally. <br> Mathematical areas of interest are partial differential equations, dynamical systems, and multiscale and singular perturbation analysis. Methods of mathematical analysis are used to formulate the models and to study the spatio-temporal behaviour of solutions, such as stability and dependence on characteristic scales, geometry, and sensitivity to initial data and key parameters. <br> <br> <b>Our analytical research includes:</b> <br> (1) Analysis of nonlinear structured population models; linking continuous and discrete structures; <br> (2) Analysis of pattern formation mechanisms in the systems of reaction-diffusion type; <br> (3) Derivation of effective models from first-principles to describe transport of cells and molecules through heterogeneous media such as biological tissues. <br> One area of focus is related to models of growth, transport and transformation processes in spaces reflecting within-population heterogeneity. Another area of focus involves new mathematical models of symmetry breaking and pattern formation in multicellular systems and analysis of a variety of pattern formation mechanisms.  Particular attention is paid to methods of model upscaling and reduction allowing derivation and analysis of tractable models of complex processes. <br> <br> <b>Applications in biology and medicine:</b> Mathematical models and methods developed by the group are applied to specific problems of developmental and cell biology. <br> <br> <b>(1)</b> <b>Stem cell dynamics in development, regeneration and cancer</b> <br> The first area of focus is mathematical modeling, analysis, and simulation of dynamics of stem cell self-renewal, differentiation, and clonal evolution in different contexts. Our interdisciplinary research is part of the Collaborative Research Center (SFB 873) “Maintenance and Differentiation of Stem Cells in Development and Disease’’. <br> <br> Our current research is devoted to: <br> - mathematical modelling the plant meristem development providing mechanistic understanding of meristem regulation and mutant phenotypes (collaboration with the group of Jan Lohmann, COS, Heidelberg University); <br> - mathematical modelling of stem cell-based development of the fish respiratory organ (collaboration with the group of Lazaro Centanin, COS, Heidelberg University); <br> - mathematical modelling of aging and regeneration in adult neurogenesis (collaboration with the laboratories of Ana Martin-Villalba, DKFZ, Heidelberg and Francois Guillemot, Francis Crick Institute, London); <br> - modelling of healthy and cancerous hematopoiesis, including blood regeneration, development of acute leukemias, clonal selection and resulting therapy resistance in blood cancers (collaboration with hematologists Anthony D. Ho, Carsten Müller-Tidow and Christoph Lutz, Heidelberg Medical Clinic); <br> Our research in mathematical hematology became part of the newly established interdisciplinary Thematic Research Network “Integrative Blood Biology Network (iBLOOD): From Basic Molecular Mechanisms to Advanced Cellular Therapies” (Heidelberg University and German Cancer Research Center). <br> <br> <b>(2)</b> <b>Pattern formation</b> <br> The second, related, line of our research is modelling, analysis and simulation of symmetry breaking and pattern formation in developmental biology. The related applications oriented research is part of the Collaborative Research Center (SFB) 1324 “Mechanisms and functions of Wnt signaling”. <br> The focus of our current project is: -mathematical modelling of symmetry breaking and pattern formation in Hydra; in parcticular mechanisms and fuction of spatio-temporal Wnt signalling and of mechano-chemical interactions (collabration with experimental groups of Thomas Holstein and Suat Özbek, COS, Heidelberg University). <!--<b>Research focus:</b> The interdisciplinary expertise of Anna Marciniak-Czochra (AMC) lies in the areas of applied mathematics and mathematical and computational biosciences. Specifically, her research focus is mathematical modelling and analysis of dynamics of self-organisation and structure formation in multicellular systems and developing new mathematical methods for modeling of such complex processes. The research combines rigorous mathematical techniques, innovative mathematical modeling and computation, with a close collaboration with experimentalists and clinicians. Mathematical areas of interest are partial differential equations, dynamical systems, and multiscale and singular perturbation analysis. Methods of mathematical analysis are used to formulate the models and to study the spatio-temporal behaviour of solutions, such as stability and dependence on characteristic scales, geometry, and sensitivity to initial data and key parameters. <br><br> The main lines of AMC’s analytical research are devoted to <br> <b>(i)</b> <b>nonlinear discrete and continuous structured population models</b> and <br> <b>(ii)</b> <b>mechanisms of pattern formation in partial and integro-differential equations</b>.<br> <br><br> One area of focus concerns models of growth, transport and transformation processes in spaces reflecting within-population heterogeneity. Another area of focus involves new mathematical models of symmetry breaking and pattern formation in multicellular systems and analysis of a variety of pattern formation mechanisms.  Particular attention is paid to methods of model upscaling and reduction allowing derivation and analysis of tractable models of complex processes. <br><br> The models developed by AMC and collaborators were successfully applied to stem cell processes and developmental pattern formation; in particular, to investigate evolution of clonal heterogeneity [Busse et al. 2022, Busse et al. 2016, Stiehl et al. 2014] and disease dynamics in acute leukemias [Stiehl et al. 2020, Stiehl et al. 2018, Wang et al. 2017, Stiehl et al. 2015], cell fate control in organ development [Danciu et al. 2022, Klawe et al. 2020, Stolper et al. 2019, Gaillochet et al. 2017], age-dependent changes in adult neurogenesis [Harris et al. 2021, Kalamakis et al. 2019, Ziebell et al. 2018] and symmetry breaking and axes formation in Hydra [Ziegler et al. 2021, Mercker et al. 2015, Marciniak-Czochra 2006]. <br><br> New models constructed by AMC often lead to mathematical challenges and require, or inspire, original approaches and techniques of model analysis and simulation. Among others, she contributed to the development of a functional analytic framework for analysis of structured population models in spaes of nonnegative Radom measures [Gwiazda et al. 2014, Gwiazda et al. 2010, Gwiazda et al. 2010], showed how to describe discrete and continuous dynamics of cell differentiation in such setting [Gwiazda et al. 2012] and developed approaches for upscaling and reduction of differential equation models. The latter included rigorous quasi-stationary and large diffusion approximations [Kowall et al. 2021, Marciniak-Czochra et al. 2018], and derivation of upscaled models of multi-scale systems [Marciniak-Czochra et al. 2015, Carraro et al. 2015, Marciniak-Czochra et al. 2014, Marciniak-Czochra et al. 2012, Marciniak-Czochra et al. 2008]. A close collaboration with numerical research groups (Peter Bastian and Robert Scheichl, IWR, Heidelberg University, Thomas Richter, University of Magdeburg) led to the development of cutting-edge methods for model simulation [Brinkmann et al. 2018, Merckeret al. 2013, Carraro et al. 2013] and recently resulted in a computational framework for Bayesian parameter estimation and model selection for partial differential equations. <br><br> <b>Applications in biology and medicine:</b> Mathematical models and methods developed by the AMC group are applied to specific problems of developmental and cell biology, as listed further below. <br><br> <b>(1)</b> <b>Stem cell dynamics in development, regeneration and cancer </b> <br> The first area of focus is mathematical modeling, analysis, and simulation of dynamics of stem cell self-renewal, differentiation, and clonal evolution in different contexts. AMC’s interdisciplinary research is part of the Collaborative Research Center (SFB 873) “Maintenance and Differentiation of Stem Cells in Development and Disease’’. <br><br> In close collaboration with developmental biologists (Lazaro Centanin and Jan Lohmann, COS, Heidelberg University), the research group of AMC works on multi-scale models of stem cell-initiated organogenesis. They built models of plant meristem development providing mechanistic understanding of meristem regulation and mutant phenotypes [Klawe et al. 2020, Gaillochet et al. 2017]. Furthermore, they proposed models identifying functional heterogeneity of stem cells in development of the fish respiratory organ [Danciu et al. 2022, Stolper et al. 2019]. <br><br> The role of intercellular heterogeneity is also the topic of AMC’s research in aging and regeneration in adult neurogenesis (collaboration with experimental labs of Ana Martin-Villalba, DKFZ, Heidelberg and Francois Guillemot, Francis Crick Institute, London). Integrating mathematical models with experimental data allowed identification of stem cell properties that change with age to compensate for the reduction of the stem cell pool and to maintain life-long neurogenesis [Harris et al. 2021, Kalamakis et al. 2019, Ziebell et al. 2018]. <br><br> In a collaboration with hematologists (Anthony D. Ho, Carsten Müller-Tidow and Christoph Lutz, Heidelberg Medical Clinic), the AMC’s group developed multi-compartment [Marciniak-Czochra et al. 2009] and structured population models [Doumic et al. 2011] that allowed them to explain observations on regeneration processes in hematopoiesis [Stiehl et al. 2014], development of leukemia [Köthe et al. 2020, Stiehl et al. 2018, Wang et al. 2017, Stiehl et al. 2015], clonal selection and resulting therapy resistance in blood cancers [Stiehl et al. 2014]. The study reveals different scenarios of possible cancer initiation and provides qualitative hints for treatment strategies. The models, combined with clinical data, may serve as a tool for personalised (targeted) therapy and provide insight into healthy and leukemic stem cell behavior in addition to molecular or biological classification of these cells. AMC’s research in mathematical hematology became part of the newly established interdisciplinary Thematic Research Network “Integrative Blood Biology Network (iBLOOD): From Basic Molecular Mechanisms to Advanced Cellular Therapies” (Heidelberg University and German Cancer Research Center). <br><br> <b>(2)</b> <b>Pattern formation</b><br> The second, related, line of AMC’s research is modelling, analysis and simulation of symmetry breaking and pattern formation in developmental biology. The related applications oriented research is part of the Collaborative Research Center (SFB) 1324 “Mechanisms and functions of Wnt signaling”. Together with the experimental groups of Thomas Holstein and Suat Özbek (Center for Organismal Studies (COS), Heidelberg University), the AMC’s reseach group investigate the role of different components of the complex spatio-temporal Wnt signalling in development and regeneration of the fresh water polyp Hydra [Ziegler et al. 2021]. They focus on models coupling non-diffusive cellular processes with diffusing signalling factors, which have been derived using homogenisation techniques [Marciniak-Czochra et al. 2008]. The results transcend the classical Turing theory [Veerman et al. 2021]. The group investigates how the structure of nonlinearities determines model dynamics and lead to pattern formation phenomena. They explore multistability and hysteresis in signalling [Köthe et al. 2020], diffusion-driven instability [Marciniak-Czochra et al. 2018, Ziebell et al. 2014, Marciniak-Czochra et al. 2013], or interplay between the two mechanisms [Härting, et al. 2017]. They also investigate a new pattern-formation mechanism based on coupling of chemical signaling with tissue mechanics, described by 4th order PDEs [Brinkmann et al. 2018, Mercker et al. 2015, Mercker et al. 2015, Mercker et al. 2013, Mercker et al. 2013]. Numerical simulations of the mechano-chemical models show symmetry breaking and formation of patterns similar to those observed in experiments [Brinkmann et al. 2018, Mercker et al. 2013]. Currently the group is working on a new approach to model identification by combining statistical methods of parameter estimation with singular perturbation analysis of the proposed hypothetical mechanisms. Implemented using parallel computer architecture in close collaboration with numerical experts (Robert Scheichl, Heidelberg Univ., and Heikki Haari, Lappeenranta-Lahti University of Technology, Finland), this methodology opens a perspective for extensions to further PDE problems and different types of data. AMC’s research on mathematical theory and tools for derivation, analysis, simulation and calibration of PDE models of pattern formation is part of the Heidelberg Cluster of Excellence “Structures”. <br><br> <b>(3)</b> <b>Systems Medicine</b> <br> It is important to develop models that may contribute not only to a mechanistic understanding of the underlying processes but also to integration of this knowledge with experimental and patient data and providing a tool for patient stratification, risk prediction and treatment planning. AMC’s research group focus on mathematical hematology projects, working on applications of mathematical models to acute myeloid leukemia [Stiehl et al. 2020, Stiehl et al. 2015], and multiple myeloma (collaboration with Heidelberg Medical Clinic V). <br><br> During recent years our research has been supported by funding from a number of sources, for example ERC Starting Grant, German Research Council (DFG), Emmy Noether Programme and Cluster “Structures” of the Excellence Strategy, Humboldt Foundation, Federal Ministry of Education and Science (BMBF) and Heidelberg Academy of Sciences and Humanities. --> <br> <br> <br> <!-- <tr> <td><img src="images/puzzleFull_map.svg" alt="puzzle" style="height:246.8718px; width:290.3754px"></td> </tr> --> <!-- <table style="border-collapse: collapse; border: none;border-spacing: 0"> <tr style="height:100px; padding: 0; margin: 0;"> <th style="width:290.3754px; padding: 0; margin: 0;"><h2 style="background-color:rgb(233, 233, 233);text-align:center;">Method development and Model analysis</h2></th> <th style="width:290.3754px; padding: 0; margin: 0;"><h2 style="background-color:rgb(31, 71, 15);text-align:center;">Modelling and Applications</h2></th> </tr> <tr style="height:246.8718px; padding: 0; margin: 0;font-size: 0px; line-height: 0px"> <td style="width:290.3754px;padding: 0; margin: 0;font-size: 0px; line-height: 0px"><a href="http://www.biostruct.uni-hd.de/folder_people/people.php"><img src="images/p1.svg" alt="piece1" style="height:246.8718px; width:290.3754px"></a></td> <td style="width:290.3754px;padding: 0; margin: 0;font-size: 0px; line-height: 0px"><a href="http://www.biostruct.uni-hd.de/folder_publications/publications.php"><img src="images/p2.svg" alt="piece2" style="height:246.8718px; width:290.3754px"></a></td> </tr> <tr style="height:246.8718px;padding: 0; margin: 0;font-size: 0px; line-height: 0px"> <td style="width:290.3754px;padding: 0; margin: 0;font-size: 0px; line-height: 0px"><a href="http://www.biostruct.uni-hd.de/folder_theses/theses.php"><img src="images/p3.svg" alt="piece3" style="height:246.8718px; width:290.3754px"></a></td> <td style="width:290.3754px;padding: 0; margin: 0;font-size: 0px; line-height: 0px"><a href="http://www.biostruct.uni-hd.de/folder_funding/funding.php"><img src="images/p4.svg" alt="piece4" style="height:246.8718px; width:290.3754px"></a></td> </tr> </table> --> </div> </div> </div> <div id="bottom"></div> <div id="bottomright"></div> </div> </body> </html>

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