My interdisciplinary lab works at the interface of microfluidics, systems biology, synthetic biology, and diagnostics. We are primarily concerned with acquiring precision measurements, often in high-throughput, of complex biological systems. In the past we contributed to transcription factor biophysics and transcriptional regulation, through in vitro and in vivo measurements. More recently we expanded our scope to large-scale single cell analysis, creation of synthetic genetic networks, and molecular diagnostics. Our current research foci fall into three ”Grand-Challenges”: i) biosystems engineering, ii) gene and genome synthesis, and iii) next generation personal diagnostics.
We continue our research on deconstructing and reconstructing transcriptional regulatory networks (TRNs) to derive quantitative models of transcriptional regulation. We are uniquely positioned to collect large-scale quantitative data on TRNs both in vitro and in vivo using our established MITOMI devices, large-scale single cell imaging platform, and our microfluidic nanoreactors for bottom up design and implementation of TRNs. Specifically, we continue our work on characterizing native transcriptional regulatory networks such as the phosphate system in S. cerevisiae. We believe that a two-pronged approach encompassing the quantitative analysis of native TRNs and construction of de novo TRNs will be particularly fruitful. In the near term we plan to develop a quantitative model of networks consisting of dozens of genes. In the longer term we envision developing a global model of transcriptional regulation in yeast.
Gene and genome synthesis:
Engineering biological systems is currently severely limited for three main reasons: i) lack of quantitative data on biological components and systems, ii) lack of quantitative models, and iii) lack of methods capable of rapidly and cheaply assembling genes and genomes. We have been and are continuing to address the first two limitations by developing novel technologies allowing us to quantitatively characterize complex biological systems. To address the latter point we have been developing novel gene synthesis approaches allowing us to generate hundreds to thousands of synthetic genes. Our novel gene synthesis approaches are tightly integrated with our MITOMI platform allowing us to rapidly synthesize, express, purify, and characterize hundreds of novel proteins in 1-2 days. In the near future we hope to conduct massively parallel gene synthesis on microfluidic devices. Such approaches will be instrumental in advancing protein engineering and in basic protein biochemistry. In the longer term we expect to expand these approaches to create genome sub-assemblies for rapid and cost-effective genome engineering.
Many of the microfluidic approaches we developed over the years are directly applicable to molecular diagnostics. Microfluidic devices will be instrumental in developing next generation, sophisticated point-of-care devices for health monitoring. We have developed several new devices for high-throughput diagnostics and protein quantitation. Most recently we developed a microfluidic device capable of measuring up to 384 biomarkers in parallel. The device can be pre-assembled and stored at ambient conditions for up to 4 weeks, enabling point-of-care diagnostics. I believe that in the near future it will be possible to develop highly integrated and sophisticated devices capable of measuring a multitude of biomarkers at marginal cost and to ubiquitously deploy these in clinics and private homes. The consequence will be significant improvements in disease diagnosis, monitoring of disease progression, and increasing treatment efficacy. Equally important will be the vast amounts of data that could be collected by such systems, which, when combined with genomics, could lead to more efficient personalized treatment regimes.