The innovation menagerie: New institutional structures are expanding horizons for early-stage research.

Academia is a vital source of innovation and discovery, but it faces challenges in funding and coordination. These challenges limit the scope and impact of academic research. Now, philanthropists and governments are exploring new institutional structures and funding strategies, with the goal of unleashing scientific discovery.

RNA timestamps identify the age of single molecules in RNA sequencing.

Current approaches to single-cell RNA sequencing (RNA-seq) provide only limited information about the dynamics of gene expression. Here we present RNA timestamps, a method for inferring the age of individual RNAs in RNA-seq data by exploiting RNA editing. To introduce timestamps, we tag RNA with a reporter motif consisting of multiple MS2 binding sites that recruit the adenosine deaminase ADAR2 fused to an MS2 capsid protein.

Slide-seq: A scalable technology for measuring genome-wide expression at high spatial resolution.

Spatial positions of cells in tissues strongly influence function, yet a high-throughput, genome-wide readout of gene expression with cellular resolution is lacking. We developed Slide-seq, a method for transferring RNA from tissue sections onto a surface covered in DNA-barcoded beads with known positions, allowing the locations of the RNA to be inferred by sequencing. Using Slide-seq, we localized cell types identified by single-cell RNA sequencing datasets within the cerebellum and hippocampus, characterized spatial gene expression patterns in the Purkinje layer of mouse cerebellum, and defined the temporal evolution of cell type-specific responses in a mouse model of traumatic brain injury.

A theoretical analysis of single molecule protein sequencing via weak binding spectra.

We propose and theoretically study an approach to massively parallel single molecule peptide sequencing, based on single molecule measurement of the kinetics of probe binding (Havranek, et al., 2013) to the N-termini of immobilized peptides. Unlike previous proposals, this method is robust to both weak and non-specific probe-target affinities, which we demonstrate by applying the method to a range of randomized affinity matrices consisting of relatively low-quality binders.

3D nanofabrication by volumetric deposition and controlled shrinkage of patterned scaffolds.

Lithographic nanofabrication is often limited to successive fabrication of two-dimensional (2D) layers. We present a strategy for the direct assembly of 3D nanomaterials consisting of metals, semiconductors, and biomolecules arranged in virtually any 3D geometry. We used hydrogels as scaffolds for volumetric deposition of materials at defined points in space.

Multiplexed neural recording along a single optical fiber via optical reflectometry.

We introduce the design and theoretical analysis of a fiber-optic architecture for neural recording without contrast agents, which transduces neural electrical signals into a multiplexed optical readout. Our sensor design is inspired by electro-optic modulators, which modulate the refractive index of a waveguide by applying a voltage across an electro-optic core material. We estimate that this design would allow recording of the activities of individual neurons located at points along a 10-cm length of optical fiber with 40-μm axial resolution and sensitivity down to 100  μV using commercially available optical reflectometers as readout devices.