The ultimate objective of this research project is to develop a microdevice platform that can enable the measurement of a single cell simultaneously for genomic, transcriptomic, proteomic and phenotypic parameters, in other words, at all the levels of the Central Dogma(DNA to RNA to protein to phenotype). Specifically, the PI will develop a microfluidic device for reliably separating cytoplasmic and nuclear contents from the same single cells followed by whole-pool amplification of genomic DNAs and messenger RNAs. The amplified products will be retrieved and analyzed using state-of-the-art genomics technology to link single-cell genetic variation to the expression of affected genes across the whole genome. Single-cell, multiplex protein assay and quantitative analysis of cellular behaviors (phenotype) can be integrated within this microdevice to further correlate genes, transcripts to the levels of proteins and cellular functions. The PI will apply this platform to investigating stem cell differentiation and potentially provide new insights needed for understanding how gene expression is regulated to determine stem cell fate and diversity. Such analysis is critical to fully addresse a range of fundamental biological questions such as embryonic development, cancer and immune cell diversity.
This project also acts as a backbone for the integration of research and educational activities spanning from K12 through graduate training, from Yale University through the local community. Integrating microtechnology into biology represents an urgent requirement of expertise for the future health science researchers and medical practitioners. The synergy of research and education will result in the development of a virtual micro-physiologic system lab for demonstration to not only Yale College students but also to the general public, and increase the participation of minorities and under-represented groups.
Due to the interdisciplinary nature of the project, this CAREER award by the Biotechnology, Biochemical, and Biomass Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biology.
