Engineering branching networks through synthetic turing morphogen circuits

Just a few years before his death, the famous mathematician and computer scientist Alan Turing proposed a model for the formation of many kinds of complex biological structures. In this model, two different chemicals spread from different release points in a developing creature, ultimately meeting and interacting at different concentrations that have a patterning effect on the organism’s development. This elegant model has been used to explain cat’s striping and spotted patterns, animal digit formation, hair and feather growth, and the branching structure of mammalian lungs. Most of these examples remain theoretical, but Wilson Wong, Ph.D., Chris Chen, M.D., Ph.D., and Darrell Kotton, M.D. are leading a project to test whether Turing’s model is responsible for the fractal-like branches of our lungs. The researchers will develop new tools to genetically engineer lung cells derived from human stem cells and attempt to recreate lung tissue’s complex branching in the lab. Ultimately, these tissues could be used in therapeutics for lung cancer and other lung diseases. 

Affiliated Investigators

Wilson Wong, Ph.D.

Boston University

Dr. Wilson Wong is an Associate Professor of Biomedical Engineering at Boston University.  He is also a founding member of the Biological Design Center. He received his B.S. and Ph.D. in Chemical Engineering from UC Berkeley and UCLA, respectively. He obtained his postdoctoral training from UCSF. Dr. Wong's lab combines engineering, biological network design, molecular biology, and immunology to develop genetic tools for basic biomedical research and cell and gene therapy.  A specific goal is to design robust and reliable methods to perform complex cellular computations in a spatiotemporally controlled manner, which will have significant implications in engineering complex tissues and designing cellular therapy with improved safety and specificity. Dr. Wong's research has been recognized by the NIH Director's New Innovator Award, NSF CAREER Award, ACS Synthetic Biology Young Investigator Award, and the College of Engineering Early Career Excellence in Research Award.

Darrell Kotton, Ph.D.

Boston Medical Center/Boston University Center for Regenerative Medicine

Dr. Darrell Kotton is the founding Director of the Boston Medical Center/Boston University Center for Regenerative Medicine and oversees program development while coordinating the efforts of six physically-contiguous laboratories in their efforts to understand basic reprogramming mechanisms as well as approaches to the directed differentiation of pluripotent stem cells, following lessons from developmental biology to derive a variety of cell lineages for basic studies and disease models.
 
Dr. Darrell Kotton’s laboratory specializes in stem cell biology with a focus on applying stem cells to model and understand lung development and disease. He has trained graduate students and post-doctoral fellows who have gone on to become faculty members in academic medicine, laboratory PI’s, and industry scientists. In his role as an educator, he serves as the PI of the Boston University CTSI’s TL1 training grant in regenerative medicine. Dr. Kotton’s laboratory research has focused primarily on applying mouse and human pluripotent stem cells to investigate the developmental biology of endoderm and the biology of lung injury and repair. His group has developed reprogramming methods, endodermal differentiation protocols for pluripotent stem cells, and gene transfer methods to modulate stem cells or various resident lung cells for durable in vitro and in vivo gene expression. Most recently his laboratory has developed new approaches for generating lung and thyroid lineages from mouse or human pluripotent stem cells in vitro.

Christopher S. Chen

Boston University

Christopher S. Chen, M.D., Ph.D., is the William Fairfield Warren Distinguished Professor of Biomedical Engineering at Boston University, Founding Director of the Biological Design Center, and member of the Wyss Institute for Biologically Inspired Engineering at Harvard University. He also serves as Deputy Director of the National Science Foundation Engineering Research Center in Cellular Metamaterials and Co-PI of the National Science Foundation Science and Technology Center for Engineering Mechanobiology. Dr. Chen has been an instrumental figure in the development of engineered cellular microenvironments to understand and control how cells build tissues. He has served, or is currently serving, as a member of the American Institute for Medical and Biological Engineering, Faculty of 1000, the Defense Sciences Study Group, and on numerous advisory boards and councils. He received his A.B. in Biochemistry from Harvard, M.S. in Mechanical Engineering from M.I.T., Ph.D. in Medical Engineering and Medical Physics from the Harvard-M.I.T. Health Sciences and Technology Program, and M.D. from the Harvard Medical School.