CAREER: The Landscape of Differentiation: Understanding the Mesenchymal Stem Cell Response to the Topography and Geometry of their Environment

Colorado State University, Fort Collins CO

Investigators

Abstract

The goal of this research project is to develop a causal mechanistic understanding of the response of bone marrow stromal cells (MSCs) to the topography of the surfaces that they are cultured on, utilizing mathematical models and experiments. While the primary focus is on MSCs, many of the questions being addressed are relevant to other mammalian cells. Theoretical models will be developed of cell spreading, adhesion and cell shape on smooth surfaces and on nano-patterned surfaces. Computational signaling models will be built that uncovers the linkages between cell shape and the differentiation decision of MSCs. Experiments in collaborating laboratories will facilitate model development and model validation.The project will help understand how the physical properties of the tissues themselves affect tissue maintenance (or homeostasis) through modulation of the differentiation decision of multipotent stem cells. This may be the process by means of which the extra-cellular matrix helps shape tissues. An understanding of these processes is currently lacking, and this research seeks to help fill this gap. The project will yield new insights into tissue homeostasis and development via the development of biophysical models of cells in different environments, which integrates the interactions and the feedback between the environment, the cellular cytoskeleton and signaling. The research program offers support for training graduate students, undergraduate students, school students and K-12 teachers. The main educational goal of the PI is teaching and disseminating modeling methods for biology and ecology to students at different levels, from school students to graduate students. The PI will develop an undergraduate-level course on modeling methods in biology, and incorporate research carried out in his laboratory, as well as current research from the world over, in the syllabus. Apart from training graduate students in his laboratory, the PI will offer undergraduate students and incoming freshmen, especially students from underrepresented minorities, an opportunity to participate in summer research. In collaboration with the Education and Outreach Center of the College of Natural Sciences (EOC-CNS) at CSU, the PI will develop course material and hold workshops to train K-12 teachers in the art and science of building computational models to understand complex biological and ecological phenomena using free online tools such as Netlogo. This will also be applied to ongoing K-12 projects that the EOC-CNS is currently involved. The EOC-CNS will help design the workshops, recruit teachers especially those who teach under-represented minorities, and will also help evaluate the impact of the workshops by a professional evaluator. K-12 teachers attending the workshop will be trained to incorporate computational models into their teaching, as well as into school research activity. Workshops will also be offered directly to school students, in collaboration with K12 teachers, during summer STEM camps organized by schools in Fort Collins. The emphasis will be on exploiting modeling tools such as Netlogo to make and visualize simple models that give insight into complicated phenomena, involving nonlinearity, stochasticity, feedback and synchronization. Examples will be taken from ecology and biology, and especially on modeling phenomena that K-12 students will encounter in their classes.