CAREER: Integrated Microsystems for Synthetic Biology

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"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."This proposal aims at establishing the foundational knowledge that will enable us to build synthetic multi-cellular machines. The researchers will design, fabricate and test a series of hybrid systems consisting of genetically modified bacteria, microfabricated arrays of chemical actuators and optical sensing. The broad goal of the technical work is to develop techniques for modulating synthetic signaling pathways in E. coli bacteria using chemical micro-interfaces. Aim 1 will produce a microsystem and a synthetic gene construct in which cells, guided by the microsystem, will express gene expression patterns programmed by the user. Aim 2 expands this by adding coordinated feedback into the microdevices to develop a complete hybrid two-component Turing reaction-diffusion system. Aim 3 then applies the knowledge gained in Aims 1 and 2 to transition the control from a flat culture plate onto a spheroidal assembly of cells resembling a simple multi-cellular system.The long term vision of this work is to design, build and test chemical interface microsystems that dynamically guide gene expression patterns of multi-cellular synthetic biology systems. This will require the development of both the relevant microsystems intended for sensing and communicating with cells and the synthetic gene constructs which respond to these microsystems. The United States today stands on the brink of a technological revolution, much as we did in the mid-20th century when we began to build complex electronic devices. Intellectual MeritThe work presented here employs microtechnology to make a radical paradigm shift away from the standard methods in synthetic biology which rely on homogenous populations of cells. To date, successful synthetic pattern generation has only been achieved by manually placing two different populations of cells on a cell culture plate (sender and receiver cells) and allowing them to communicate. This work intends to change this: by communicating directly with cells programmed to respond, cultures of cells can be made to develop spatial inhomogeneities in gene expression. The ability to create complex spatial patterns of gene expression, (ie. synthetic bacterial differentiation) will enable the fabrication of a new class of organic constructs built from co-operating cell populations in a manner analogous to differentiation schemes in developmental biology. Broad ImpactThe broad impact and outreach plan has five components: 1) K-12 workshops with Poplin Press and Matthew Perry to develop and test GoNano!, a card-based teaching aid for elementary and junior high students, 2) the development of both a new BioMEMS course for graduate students at UC Berkeley, based on a syllabus on which the PI has published, and a new core MEMS course for undergraduates (which, surprisingly, does not exist in EECS at UC Berkeley), 3) leadership involvement in Berkeley?s SUPERB program, of which the PI is an alumnus, 4) student exchange and BioMEMS seminars with Prof. Nelson Sepulveda at the University of Puerto Rico, Mayaguez, 5) leadership and participation in the URM community at Berkeley; the PI served as the president of the Latino Faculty & Staff Association at the University of Michigan and that experience can be applied at Berkeley.