New Tools for Systems Biology
Single Cell Transcriptomics:
Cells respond heterogeneously to chemical and genetic perturbations. The origin of this heterogeneity ranges from differences in cell morphology, microenvironment, and cell cycle stage to diversity in gene expression, epigenetic state, and genomic stability. Hence, single cell approaches are crucial to unbiased, system-wide analyses of biological samples. We are developing microfluidic devices, fluorescent probes, and sequencing tools to study transcription in individual cells.
Cell Type-Specific Translatomics:
We recently reported cell type-specific measurements of translation in the brain and in brain tumors, combining the RiboTag system with ribosome profiling and computational deconvolution. Current translatomics projects in the lab are addressing several broad questions about translational regulation, particulary in the central nervous system:
- What is the role of translational regulation in cellular differentiation and reprogramming?
- How do downstream mediators of growth signaling pathways achieve gene-specific regulation of protein synthesis?
- How do cis-regulatory elements in mRNA, including structural motifs and covalent modifications, influence translation?
Single Molecule Proteomics:
The ultimate success of the recent revolution in DNA sequencing hinges in part on the ability of proteomics to connect genomics with phenotypes. However, the tools available to reseachers and clinicians for protein analysis lag far behind those for nucleic acid analysis. This is because proteins are structurally complex and have no analog of base-pairing or template-dependent replication, making them much more difficult to identify and detect. We are leveraging recent advances in imaging, microfludics, and sequencing to tackle this important challenge with the hope of enabling proteomic analysis of individual cells.