System Biology

 Systems biology is a new science to study the interactions and interplay of many levels of biological information. Systems biology will enable us not only to cure complex diseases but also to predict an individual's health and extend the human body's natural lifespan by preventing diseases. Because of the advance in both experiments and theoretical studies, the conversion of biology into a more quantifiable science is now possible and might be the main driving force behind innovation and development in mathematics.  Subjects of our study including different biological problems such as developmental biology, biology of cancer, diabetes, and blood diseases. 

Gene Regulation in developmental biology

In this project, we will study the gene regulation network for the development of wing imaginal disc of drosophila by mathematical method. Development is a complicated biological process that controlled by a complex and subtle gene network. However, the mechanisms that how can this network operate reliably despite mutation, noisy enviroments and stochasticity in gene expression is not known. In this project, we will firstly establish a mathematical model for the gene regulation network of the development of wing imagical disc, and secondly study the robustness of the gene network when the synthesis rates of proteins are changed due to either determine or stochastic reason. Through the research of this project, we will try to help people uncovering the mechanisms behind biological phenomenon that control the stability and robustness of the development process. Furthermore, the method we development from the research of this project will be able to study the gene regualtion networks for other biological processes as well, and hence improve the quantitative research for the biological science, which may in turn stimulate the study of applied mathematics. Quantitative research for the developemental biology will help people understand the mechanisms of some inherited and geneogenous diseases, and provide theoretical foundation for treating and preventing such diseases.

During the initial phase of embryonic development, identical cells simply divide to reproduce more of the same. At some stage, signaling protein molecules known as morphogens (aka ligands) are synthesized at a localized site. These morphogens disperse from their production site; some bind to cell receptors along the way, generally resulting in different receptor occupancies at different cell locations. The spatial concentration gradient of morphogen-receptor complexes (aka bound morphogens) induces spatially graded differences in cell signaling (Figure 1). The differential cell signaling in turn gives rise to different gene expressions from which follow different stable cell fates and visually patterned arrangements of tissues and organs during development.

 

Figure 1. Morphogen gradient

 

In principle, the process of forming morphogen gradients leading ultimately to tissue patterning consists of syntheses of transportable morphogens and membrane bound cell receptors, their binding and dissociation, endocytosis and exocytosis of morphogen-receptors and their intracellular degradation. This collection of biological processes has been modelled mathematically in [6]. We also see from the mathematical model that small changes of the system parameters may cause substantial changes in gradient shape [6]. In contrast, embryonic patterning is usually highly robust, resisting not only substantial changes in the expression level of individual genes, but also fluctuating environmental conditions (e.g., unseasonal heat waves)[7]. This suggests that additional biological processes must also be at work to ensure such robustness. Identifying the cause of robustness and ways of producing robust morphogen gradients have become a major research effort in recent years [1,2,3,4,5,8,9]. This project will seek to discover the mechanisms by which the robust morphogen gradient is produced.

Bibliography

 

1. A. ELDAR, R. DORFMAN, D. WEISS, H. ASHE, B. Z. SHILO AND N. BARKAI, Robustness of MmP morphogen gradient in Drosophila embryonic patterning, Nature 419(2002), pp. 304-308.

2. A. ELDAR, D. ROSIN, B. Z. SHILO AND N. BARKAI, Self-enhanced ligand degradation underlies robustness of morphogen graients, Dev. Cell, 5(2003), pp. 635-646.

3. A. ELDAR, B.Z. SHILO AND N. BARKAI, Elucidating mechanisms underlying robustness of morphogen gradients, Curr. Opin. Genet. Dev., 14(2004), pp. 435-439.

4. B. HOUCHMANDZADEH, E. WIESCHAUS AND S. LEIBLER, Establishment of developmental precision and proportions in the early Drosophila embryo, Nature, 415(2002), pp. 798-802.

5. N.T. INGOLIA, Topology and robustnessin the Drosophila segment polarity network, PLoS Biol., 2(2004), pp. 0805-0815.

6. A. D. LANDER, Q. NIE AND F. Y. M. WAN, Do morphogen gradients arise by diffusion? Dev. Cell 2(2002), pp. 785-796.

7. S. MORIMURA, L. MAVES, Y. CHEN, F. M. HOFFMANN, decapentaplegic Overexpression affects drosophila wing and leg imaginal disc development and wingless expression, Dev. Biol. 177(1996), pp. 136-151.

8. G. VON DASSOW, E. MEIR, E. M. MUNRO AND G. M. ODELL, The segment polarity network is a robust developmental module, Nature, 406(2000), pp. 188-192.

9. G. VON DASSOW, AND G. M. ODELL, Design and constraints of the Drosophila segment polarity module: robust spatial patterning emerges from intertwined cell state switches, J. Exp. Zool., 294(2002), pp. 179-215.

 

Research Team:

  

Jin-Zhi Lei

Associate Researcher

  

Xiao-Juan Sun

Postdoc

  

Chang-Jing Zhu-Ge

Ph.D sutdent