This NSF award by the Office of Emerging Frontiers in Research and Innovation supports a collaboration between investigators at Rice University and the University of Washington to engineer bacterial stem cells to grow and divide into a wide variety of multicellular patterns and structures. In biology, multicellular tissues and organisms arise from undifferentiated stem cells via complex processes of embryogenesis and development. How large numbers of noisy and error-prone biological cells precisely coordinate their actions over space and time remains an open and challenging question. Here the investigators will take an engineering approach to this problem, by constructing a model multicellular "developmental" system in the bacterium E. coli. The genetics of E. coli are well understood and the organism is therefore very amenable to engineering. Moreover, because E. coli does not naturally form patterns, it is a blank slate where any pattern formed can be more easily attributed to the engineered genetic program.
This research program combines immediate practical impact with conceptual depth. The proposed work will enable a potentially transformative technology for controlling the growth of tissues and higher order cellular structures through engineered cell-cell communication. The approach incorporates key features of biological pattern formation, such as (i) the use of positional information encoded within gradients of extracellular signals, (ii) intercellular communication, (iii) feedback and signal processing and (iv) epigenetic inheritance of states. The investigators will develop and quantitatively characterize molecular devices for implementing each of these core functionalities and will then modularly combine those elements into increasingly complex pattern-forming circuits. Experimental work will be guided by mathematical modeling and will take advantage of a custom-made programming formalism for specifying desired shapes and patterns. This group of investigators has highly complementary expertise in signal processing, cell-cell signaling, distributed computing and synthetic biology. This will allow the investigators to produce a combined experimental-computational design cycle that will accelerate the rate of progress in this challenging and important research area.
This technology will have great scientific, economic and societal impact. The last decade of synthetic biology boasted a series of significant advances in engineering cellular sensing and signal transduction and constructing synthetic DNA at large scale. Harnessing these advances for the engineering of coordinated multicellular behaviors, best exemplified in pattern formation, is now a major goal in the field. This collaborative effort will significantly advance the current state of the art in programmed pattern formation by developing a rigorous framework to engineer a single stem cell to grow and differentiate into any arbitrary pattern. The outcomes of this work will impact developmental biology, tissue engineering, regenerative medicine, metabolic engineering and biomaterials research.
This work is tightly integrated with an outreach program that has two main goals. The first goal is to develop an educational program to teach students the interdisciplinary skills necessary to be successful in synthetic biology. To achieve this goal, the PIs are developing a three course curriculum that is coordinated between several departments at Rice University and the University of Washington. The second goal is to increase the participation of women and underrepresented minorities in engineering disciplines. This will be achieved through established outreach programs aimed at high school teachers, incoming freshmen, underrepresented minorities and women. In particular, the PIs will develop new biological teaching tools that take advantage of the visually compelling experimental systems constructed here.
