• Greenleaf Lab
    Department of Genetics, Stanford University School of Medicine
    Research Interests
    Our lab focuses on developing methods to understand the relationship between sequence, structure,
    and function of the genome and epigenome. Our efforts are split between building new tools to leverage
    the power of high-throughput sequencing and cutting-edge microscopies, and bringing these new technologies
    to bear against basic biological questions of genomic and epigenomic variation.
  • Ultra high-throughput
    RNA-protein biophysics
    On-chip binding of >140k RNA variants
    Summary
    We demonstrate how RNA-MaP can provide detailed insight
    into the biophysical basis and evolutionary consequences of
    sequence-function relationships.
  • Fast & sensitive epigenomic profiling
    ATAC-seq profiles chromatin accessibility with the Tn5 transposase
    Summary
    Using an enzyme known as Tn5 transposase, we preferentially tag and sequence DNA from open chromatin.
    This method, which we've termed ATAC-seq, provides similar information to that of new DNase-seq methods,
    but its protocol is simpler and requires far fewer cells. This opens up the possibility of applying it to a much
    broader collection of samples.
  • We are interested in the intersection between biophysics and evolution.
     By modeling the propensity of binding in a graph of 620,100 mutations, we determined
     the prevalence of epistasis in the evolution of RNA-protein interactions.
  • We are building instrumentation to enable ultra-high-throughput biophysics.
     We aim to uncover single-molecule dynamics and short-lived nucleic-acid conformations hidden
     in “bulk” biochemical methods critical for accurate physical understanding of biopolymers.
  • We are integrating tools from biophysics, genomics, and computer science
    to –for example– probe structure-function relations in RNA-protein interactions.
  • We are located on the beautiful Stanford University campus.

Intro: Understanding the Physical Genome

Our lab focuses on developing methods to probe both the structure and function of molecules encoded by the genome, as well as the physical compaction and folding of the genome itself. Our efforts are split between building new tools to leverage the power of high-throughput sequencing technologies and cutting-edge optical microscopies, and bringing these technologies to bear against basic biological questions by linking DNA sequence, structure, and function.

High-throughput Biophysics & Molecular Evolution

We are interested in understanding the biophysical basis and evolutionary consequences of sequence-function relationships in biological molecules and their interactions. Towards this goal, we develop ultra-high-throughput methods to quantitatively assay sequence-space in bulk and single-molecule experiments.

DNA Accessibility & Chromatin Structure

We seek to understand the hierarchical folding of genomic DNA into regulated structures, the most basic and important of which is the nucleosome. With this objective in mind, we have developed methods that assay open chromatin, nucleosome positions, and transcription factor binding genome-wide in small populations of cells undergoing dynamic processes such as differentiation or stochastic state switching.

Sound interesting?

We are actively recruiting students and postdoctoral fellows to work on these and other projects in the lab.

Join Us!