• Meagher, Laurence
• Condie, Glenn
• Andrade, Jess
• Werkmeister, Jerome
• Haylock, David
• Tarasova, Anna
• Winkler, Dave

Abstract

Regenerative medicine offers exciting new prospects for repairing or replacing tissues damaged by accident and disease. Additionally, the role of aberrant stem cells (cancer stem cells) in causing serious malignant disease is becoming clearer, offering new ways of fighting cancers by reprogramming these cells or causing them to undergo normal differentiation or apoptosis. Consequently there is a vast experimental research effort into understanding factor that drive stem cell fate, and in controlling them. Paradoxically, this huge experimental effort has not been matched by theoretical or computational research into stem cell behaviour and properties. Such study would provide a strong conceptual, theoretical, and computational framework to interpret experimental results, and to plan new experiments. About five years ago my group recognized the opportunities that this paucity of non-experimental research effort provided, and we moved a substantial segment of our modelling work into stem cells, aided by the collocation of the Australian Stem Cell Centre on campus.Our work covers a broad range of activities from: development of theoretical, conceptual models of self organization and criticality in stem cell regulatory networks; novel coarse methods for selecting critical genes from gene expression microarray data; simple, coarse-grained models of stem cell gene regulatory networks that can recapitulate microarray expression levels; nonlinear dynamical models of core regulatory switch circuitry that control fate determination, predictive modelling of stem cell bioreactor properties; anddesign of small molecule cytokine and extracellular matrix mimetics that control stem cell fates.This paper will focus on the design, synthesis and biological activities of small molecule and peptide mimics of cytokines, growth factors, and cell adhesion factors that modulate stem cell growth and differentiation.This work is aimed at developing new therapeutic drugs, smart materials that can provide specific signals to cells, and agents that allow control of cell adhesion for therapeutic and cell culture purposes.1. Towards a Rosetta stone for the stem cell genome: stochastic gene expression, network architecture and external influences, Halley, JD, Winkler, DA, Burden, FR. Stem Cell Res. 1, 157-168 (2008) 2. Modelling atypical small molecule mimics of an important stem cell cytokine, thrombopoietin, Anna Tarasova, David Winkler, ChemMedChem. 4, 2002-2011 (2009). 3. Stem cell decision-making and critical-like exploratory networks, Julianne D. Halley, Frank R. Burden, David A. Winkler, Stem Cell Res. 2, 165–177 (2009). 4. Predictive Mesoscale Network Model of Cell Fate Decisions during C. elegans Embryogenesis, Winkler DA, Burden, FR, Halley, JD, Artif. Life, 15(4), 411–421 (2009). 5. Zinc is not essential for activity of TPO receptor agonists acting at the transmembrane domain, Jessica Andrade, Glenn Condie, David Haylock, Laurence Meagher, Andrew Riches, Anna Tarasova, Jacinta White, David Winkler, ACS Chem. Biol. 5, 741-745 (2010).6. Tripeptide motifs in biology as drug targets, Ung, Phuc, Winkler, DA, J. Med. Chem. (Persp.). 54, 1111–1125, 2011.

Topics

• impedance spectroscopy
• experiment
• zinc
• temperature-programmed oxidation