Biocatalysis Beyond the Cell: Molecular Engineering Catalytic Ensembles for Cell-free Synthetic Biology

Research Statement. My research group is motivated by a desire to understand, harness, and expand the capabilities of biological systems for compelling applications in medicine, materials, and energy. Specifically, we focus on designing, constructing, and modifying biological systems involved in protein synthesis and metabolism to (i) understand why nature’s designs work the way they do and (ii) open the way to products that have been impractical, if not impossible, to produce by other means. An innovative feature of our research program is the use of cell-free systems. The foundational principle is that we can conduct precise, complex biomolecular transformations without using intact cells (Fig. 1), which provides an unprecedented and otherwise unattainable freedom of design to modify and control biological systems.1-4 For example, cell-free systems avoid the need to balance the tug-of-war that exists between the cell’s physiological and evolutionary objectives and the engineer’s process objectives. Leveraging my unique approach, and taking advantage of expertise in quantitative applied biotechnology and genome engineering, my research team has become recognized leaders in biochemical engineering and cell-free synthetic biology. Research program highlights. Highlighting my successful efforts to build a peer-recognized, self-sustained research program, my team has published in high quality specialty journals (e.g., ACS Synthetic Biology, Nucleic Acids Research), and high impact general biochemistry journals (e.g., Molecular Systems Biology). We have also submitted several provisional and full patent applications. Further, my group has been supported by a variety of funding agencies: NIH, NSF, ONR, ARO, DARPA, ARPA-E, among others. As detailed in my CV, in 11 of 16 funded projects, I am principal investigator (PI), being sole-PI in five projects. My team and I have been recognized for research excellence in several venues (see Biosketch for more details): • Packard Fellowship, NIH Pathway to Independence Award, DARPA Young Faculty Award, Agilent Early Career Professor Award, and 3M Non-Tenured Faculty Grant to MCJ, • 40+ invited lectures; including departmental and institute seminars, two international keynote addresses, and several workshops hosted by the National Academy of Sciences, • Invited Lecturer, Cold Spring Harbor Laboratory course on synthetic biology, • Associate Editor (1 of 4), ACS Synthetic Biology, and • Graduate fellowships, travel awards, poster awards to MCJ group (e.g., NDSEG, NSF GRFP, Cabell Fellowship, "Breakthrough Technology" poster award at Metabolic Engineering X (ME X)).