Imaging translational control by Argonaute with single-molecule resolution in live cells.

A major challenge to our understanding of translational control has been deconvolving the individual impact specific regulatory factors have on the complex dynamics of mRNA translation. MicroRNAs (miRNAs), for example, guide Argonaute and associated proteins to target mRNAs, where they direct gene silencing in multiple ways that are not well understood. To better deconvolve these dynamics, we have developed technology to directly visualize and quantify the impact of human Argonaute2 (Ago2) on the translation and subcellular localization of individual reporter mRNAs in living cells.

Dual roles for piRNAs in promoting and preventing gene silencing in C. elegans.

Piwi-interacting RNAs (piRNAs) regulate many biological processes through mechanisms that are not fully understood. In Caenorhabditis elegans, piRNAs intersect the endogenous RNA interference (RNAi) pathway, involving a distinct class of small RNAs called 22G-RNAs, to regulate gene expression in the germline. In the absence of piRNAs, 22G-RNA production from many genes is reduced, pointing to a role for piRNAs in facilitating endogenous RNAi.

Bead Loading Proteins and Nucleic Acids into Adherent Human Cells.

Many live-cell imaging experiments use exogenous particles (e.g., peptides, antibodies, beads) to label or function within cells.

Rapid, robust plasmid verification by de novo assembly of short sequencing reads.

Plasmids are a foundational tool for basic and applied research across all subfields of biology. Increasingly, researchers in synthetic biology are relying on and developing massive libraries of plasmids as vectors for directed evolution, combinatorial gene circuit tests, and for CRISPR multiplexing. Verification of plasmid sequences following synthesis is a crucial quality control step that creates a bottleneck in plasmid fabrication workflows.

Lighting up single-mRNA translation dynamics in living cells.

Over the past five years, technological advances have made it possible to image the translation of single mRNA in the natural context of living cells. With these advances, researchers are beginning to shed light on when, where, and to what degree mRNA are translated with single-molecule precision. These works provide insight into the heterogeneity of translation amongst single transcripts, behavior that is averaged out in complementary bulk assays.

Castration Determines the Efficacy of ETAR Blockade in a Mouse Model of Prostate Cancer Bone Metastasis.

Bone metastasis is a painful complication of advanced prostate cancer. Endothelin-1 is a tumor-secreted factor that plays a central role in osteoblast activation and the osteosclerotic response of prostate cancer metastatic to bone. Antagonists that block the activation of the endothelin A receptor (ETAR), located on osteoblasts, reduce osteoblastic bone lesions in animal models of bone metastasis.