New Tools for Systems Biology


Single Cell Genomics and 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.  For more information, please see our recent papers here and here.

We are using these tools to study phenotypic transitions that occur during the progression of solid tumors and to better understand the evolution of drug resistance in cancer.

Translatomics - Systems Biology of Protein Synthesis:

We recently reported cell type-specific measurements of protein synthesis 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:

  • How do cis-regulatory elements in mRNA, including structural motifs and covalent modifications, influence translation?
  • How do protein kinases mediate translational control of specific genes? 
We are also interested in the role of translational regulation in development and disease, particularly in the central nervous system:
  • What is the role of translational regulation in cellular differentiation and reprogramming?
  • mTOR is a master regulator of translation in mammalian cells. Hyperactivation of mTOR is a common theme in seizure-causing disorders. What are the consequences of translational dysregulation in seizure-causing disorders such as tuberous sclerosis (TSC) and glioma?
Finally, we are developing new tools for genome-wide measurements of protein synthesis including:
  • High-sensitivity approaches to ribosome footprinting (recently published here)
  • Highly-multiplexed translation measurements for genome-wide screens