Stan Marée's old webpage

I have recently moved to Norwich, where I have started as a Project Leader in the Department of Computational and Systems Biology at the John Innes Centre. My research group focuses on Modelling Animal and Plant Development.

From 2003-2009 I was a staff member of the Theoretical Biology / Bioinformatics Group, at the Utrecht University, the Netherlands.

Research interests

stan2.jpgThe main theme of my research is ``Modelling morphogenesis on the interface of subcellular and cellular processes''. Since we have entered the era of bioinformatics, we continuously gain better understanding of the processes that take place on the subcellular level. However, there is limited knowledge how the subcellular processes eventually lead to morphogenesis, how during embryogenesis tissues, organs, and whole organisms emerge and are able to grow, develop, and maintain themselves. We want to fill up the missing link between gene regulation and morphogenesis. To bridge the gap, we are coupling the cellular Potts model, a cellular automata-type of model that is very powerful for describing cell dynamics, to (minimal) models of gene regulation networks. This multi-level modelling approach, in which all the pre-defined dynamics in the model are on the (sub)cellular level, while all the interesting behaviour that emerges from the model take place at different intermediate levels of organisation, as well as at the level of the whole organism, allows us to keep a relatively low level of model-complexity, since the complexity of the morphogenesis itself emerges from the interactions and entanglement of the different levels. It provides a framework in which cells can differentiate and generate shape simultaneously, and in which experimental findings related to gene regulation can be linked to the observed development, from the cellular level to the level of the whole organism.

From 2001-2003 I have been a MITACS postdoctoral fellow working with Leah Keshet. I was a member of the Mathematical Biology research group of the Mathematics Department at the University of British Columbia.

In Vancouver, I have worked on models describing the development of Type I Diabetes. Type I diabetes is an autoimmune disease which develops after a prolonged period of inflammation of the pancreatic islets of Langerhans. The immune system specifically attacks the insulin-producing beta cells. Progression from hidden inflammation to overt diabetes is caused by an increase in the fraction of lymphocytes that have a high affinity and high toxicity to the beta cells. This is called avidity maturation. Treatment of diabetes-prone mice with peptides similar to those recognised by the lymphocytes has been observed to either speed up or slow down the avidity maturation, and thereby the development of diabetes. The outcome depends in a highly non-linear way on the dose of the administered peptide. We have developed a number of ODE models to explore the possible underlying mechanisms of the avidity maturation and its modulation by peptide treatment. The models describe the dynamics of lymphocyte populations that have different affinities for the beta cell peptide, as well as the so-called antigen-presenting cells, which present these peptides to the lymphocytes.

PhD Thesis: From Pattern Formation to Morphogenesis

I have done my PhD studies under supervision of Dr. Sasha Panfilov and Prof. Paulien Hogeweg in the Theoretical Biology / Bioinformatics group, Utrecht University, the Netherlands. In my thesis I describe a model study of the whole development of the cellular slime mould Dictyostelium discoideum.

Personal stuff

When I was living in Vancouver, I have made a couple of fantastic hikes through beautiful British Columbia. Here you can find many nice pictures of our hikes.

List of Publications

M. Laskowski, V. A. Grieneisen, H. Hofhuis, C. A. ten Hove, P. Hogeweg, A. F. M. Marée, and B. Scheres.
Root system architecture from coupling cell shape to auxin transport.
PLoS Biol., 6(12):e307 (2008). MEDLINE.

A. F. M. Marée, M. Komba, D. T. Finegood, and L. Edelstein-Keshet.
A quantitative comparison of rates of phagocytosis and digestion of apoptotic cells by macrophages from normal (BALB/c) and diabetes-prone (NOD) mice.
J. Appl. Physiol., 104(1):157-169 (2008). MEDLINE.

J. B. Beltman, A. F. M. Marée, J. N. Lynch, M. J. Miller, and R. J. de Boer.
Lymph node topology dictates T cell migration behavior.
J. Exp. Med., 204(4):771-780 (2007a). MEDLINE.

J. B. Beltman, A. F. M. Marée, and R. J. de Boer.
Spatial modelling of brief and long interactions between T cells and dendritic cells.
Immunol. Cell Biol., 85(4):306-314 (2007b). MEDLINE.

V. A. Grieneisen, J. Xu, A. F. M. Marée, P. Hogeweg, and B. Scheres.
Auxin transport is sufficient to generate a maximum and gradient guiding root growth.
Nature, 449(7165):1008-1013 (2007). MEDLINE.

A. Jilkine, A. F. M. Marée, and L. Edelstein-Keshet.
Mathematical model for spatial segregation of the Rho-family GTPases based on inhibitory crosstalk.
Bull. Math. Biol., 69(6):1943-1978 (2007). MEDLINE.

J. Käfer, T. Hayashi, A. F. M. Marée, R. W. Carthew, and F. Graner.
Cell adhesion and cortex contractility determine cell patterning in the Drosophila retina.
Proc. Natl. Acad. Sci. U.S.A., 104(47):18549-18554 (2007). MEDLINE.

A. F. M. Marée, V. A. Grieneisen, and P. Hogeweg.
The Cellular Potts Model and biophysical properties of cells, tissues and morphogenesis.
In A. R. A. Anderson, M. A. J. Chaplain, and K. A. Rejniak, editors, Single-Cell-Based Models in Biology and Medicine, pages 107-136. Birkhäuser Verlag, Basel (2007).

J. Käfer, P. Hogeweg, and A. F. M. Marée.
Moving forward moving backward: directional sorting of chemotactic cells due to size and adhesion differences.
PLoS Comput. Biol., 2(6):e56 (2006). MEDLINE. DownLoad PDF.

A. F. M. Marée, A. Jilkine, A. Dawes, V. A. Grieneisen, and L. Edelstein-Keshet.
Polarization and movement of keratocytes: a multiscale modelling approach.
Bull. Math. Biol., 68(5):1169-1211 (2006a). MEDLINE. Web Page. DownLoad PDF.

A. F. M. Marée, P. Santamaria, and L. Edelstein-Keshet.
Modeling competition among autoreactive CD8+ mathend000# T cells in autoimmune diabetes: implications for antigen-specific therapy.
Int. Immunol., 18(7):1067-1077 (2006b). MEDLINE. DownLoad PDF.

A. F. M. Marée, R. Kublik, D. T. Finegood, and L. Edelstein-Keshet.
Modelling the onset of Type 1 diabetes: can impaired macrophage phagocytosis make the difference between health and disease?
Philos. Transact. A., 364(1842):1267-1282 (2006c). MEDLINE. DownLoad PDF.

M. A. C. Groenenboom, A. F. M. Marée, and P. Hogeweg.
The RNA silencing pathway: the bits and pieces that matter.
PLoS Comput. Biol., 1(2):155-165 (2005). MEDLINE. DownLoad PDF.

B. Han, P. Serra, A. Amrani, J. Yamanouchi, A. F. M. Marée, L. Edelstein-Keshet, and P. Santamaria.
Prevention of diabetes by manipulation of anti-IGRP autoimmunity: high efficiency of a low-affinity peptide.
Nat. Med., 11(6):645-652 (2005). MEDLINE. DownLoad PDF.

A. F. M. Marée, M. Komba, C. Dyck, M. \Labeçki, D. T. Finegood, and L. Edelstein-Keshet.
Quantifying macrophage defects in type 1 diabetes.
J. Theor. Biol., 233(4):533-551 (2005). MEDLINE. DownLoad PDF.

A. F. M. Marée and P. Hogeweg.
Modelling Dictyostelium discoideum morphogenesis: the culmination.
Bull. Math. Biol., 64(2):327-353 (2002). MEDLINE. Web Page. DownLoad PDF.

A. F. M. Marée and P. Hogeweg.
How amoeboids self-organize into a fruiting body: multicellular coordination in Dictyostelium discoideum.
Proc. Natl. Acad. Sci. U.S.A., 98(7):3879-3883 (2001). MEDLINE. Web Page. DownLoad PDF.

V. Müller, A. F. M. Marée, and R. J. de Boer.
Release of virus from lymphoid tissue affects human immunodeficiency virus type 1 and hepatitis C virus kinetics in the blood.
J. Virol., 75(6):2597-2603 (2001a). MEDLINE. DownLoad PDF.

V. Müller, A. F. M. Marée, and R. J. de Boer.
Small variations in multiple parameters account for wide variations in HIV-1 set-points: a novel modelling approach.
Proc. R. Soc. Lond. B., 268(1464):235-242 (2001b). MEDLINE. DownLoad PDF.

A. F. M. Marée, W. Keulen, C. A. B. Boucher, and R. J. de Boer.
Estimating relative fitness in viral competition experiments.
J. Virol., 74(23):11067-11072 (2000). MEDLINE. Web Page. DownLoad PDF.

A. F. M. Marée, A. V. Panfilov, and P. Hogeweg.
Migration and thermotaxis of Dictyostelium discoideum slugs, a model study.
J. Theor. Biol., 199(3):297-309 (1999a). MEDLINE. Web Page. DownLoad PDF.

A. F. M. Marée, A. V. Panfilov, and P. Hogeweg.
Phototaxis during the slug stage of Dictyostelium discoideum: a model study.
Proc. R. Soc. Lond. Ser. B, 266:1351-1360 (1999b). Web Page. DownLoad PDF.

A. F. M. Marée and A. V. Panfilov.
Spiral breakup in excitable tissue due to lateral instability.
Phys. Rev. Lett., 78:1819-1822 (1997). Web Page. DownLoad PDF.

R. J. A. van Wezel, M. J. M. Lankheet, F. A. J. Verstraten, A. F. M. Marée, and W. A. van de Grind.
Responses of complex cells in area 17 of the cat to bi-vectorial transparent motion.
Vision Res., 36(18):2805-2813 (1996). MEDLINE. DownLoad PDF.

A. F. M. Marée, R. J. A. van Wezel, F. A. J. Verstraten, and W. A. van de Grind.
Processing of transparent motion information in area 17 complex cells of the cat.
Perception (suppl.), 23:57-58 (1994).

R. J. A. van Wezel, F. A. J. Verstraten, A. F. M. Marée, and W. A. van de Grind.
Responses of complex cells in area 17 of the cat to transparent motion.
Invest. Ophthalmol. Vis. Sci. (suppl.), 35:1973 (1994).

Current address

Address: Dr. Stan Marée
  John Innes Centre
  Norwich Research Park
  Colney, Norwich
Office location: Genome Centre, Room 101d
Phone: +44-1603-450828