Technology Development Initiative Paper of the Month

Highly accurate protein structure prediction for the human proteomeNature

Determining complete protein structures is difficult as sufficient quantities need to be purified; protein size, transmembrane domains, and susceptibility to conformational changes create inconsistencies; and the work can take months to years. Tunyasuvunakool et al. applied AlphaFold to predict full-length structures with detailed chemical components of nearly the entire human proteome (98.5%) as well as ~20 other organisms and provided this data in a public database. Since publication, the authors updated AlphaFold (version 2) shortening days-long prediction computation to minutes/hours and the database now has over 200 million protein structures. [Read More]

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Engineering of NEMO as calcium indicators with large dynamics and high sensitivity. Nat Methods

Current genetically encoded calcium indicators have suboptimal dynamic range and peak signal-to-baseline ratios. Li et al. engineered a new series of mNG-based calcium indicators (NEMO) that exhibit fast kinetics with up to 100-fold increase in dynamic range and 20-fold increase in signal-to-baseline ratios when NEMO sensors were compared to GCaMP6m or NCaMP7. Increased fluorescence and dynamic range of NEMO should facilitate the in vivo monitoring of calcium changes in deep brain structures and cellular organelles. [Read More]

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Revealing the structure of pharmacobehavioral space through motion sequencing. Nat Neurosci.

Standard behavioral assays that are used for screening candidate therapeutic drugs, such as the elevated plus maze and forced swim test, yield only one or two dimensions of information. Wiltschko et al. used a machine learning algorithm called MoSeq (for motion sequencing) to analyze 3D video recordings of twenty minutes of open field mouse activity, thereby obtaining a much higher dimensional readout of behavior in response to a wide variety of psychoactive drugs and doses. [Read More]

The Successor Representation: Its Computational Logic and Neural Substrates. J Neurosci.

In this paper, Gershman presents and builds upon a reinforcement learning algorithm first proposed by Peter Dayan in 1993, called the successor representation, which solves some important problems that previous classes of reinforcement learning algorithms have had.  Recent research has supported the idea that humans and other animals use successor representations for learning and decision making under some conditions and has proposed that dopaminergic mechanisms could build successor representations in the brain. [Read More]

Customizable, wireless and implantable neural probe design and fabrication via 3D printing. Nature Protocols.

Detailed in this protocol are custom manufacturing techniques for rapidly 3D-printing large number of optogenetic probes of any length and number of shanks. Also included are instructions for low-cost, custom, wireless harnesses to couple with probes for offsite optical manipulation. [Read More]

Insights into distinct signaling profiles of the µOR activated by diverse agonists. Nat Chem Biology.

The TRUPATH BRET2 assay is a single and comprehensive platform of 14 G protein biosensors that allows for unambiguous measurement of heterotrimeric G protein dissociation following agonist-induced receptor stimulation. Because individual G protein subunits have distinct functional characteristics, directly monitoring their activation and signaling profiles provides new opportunities for revealing previously uncharacterized actions of GPCR ligands. [Read More]

Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging. Cell.

A group of researchers from Stanford University employed a multiplexed mass cytometry to profile the epigenetic landscape and measure a broad array of global chromatin modifications in human cells at the single-cell level. The EpiTOF technology provides new opportunities for identifying cell-specific epigenetic changes associated with altered physiological and pathological states. [Read More]

Polony gels enable amplifiable DNA stamping and spatial transcriptomics of chronic pain. Cell.

Fu*, Sun*, Dong* et. al. generated and validated a novel polony-based ‘stamp gel’ that uses common lab equipment and enzymatic replication to produce copies of the 1 µm resolution barcoded array slide that is used for spatial transcriptomic capture. Taken together, polony gel stamping is poised to increase accessibility of high-resolution spatial transcriptomics. [Read More]

Rapid Quantum Magnetic IL-6 Point-of-Care Assay in Patients Hospitalized with COVID-19. Diagnostics.

The quantum diamond microscope system is a sensitive method to detect target proteins in a short time compared to similar immunocomplex-based detection methods (e.g. traditional ELISAs). This method does not require removal of unbound beads or extensive wash steps thus providing relatively fast and sensitive assay for measuring protein targets in pre-clinical and clinical applications. [Read More]

Nanoparticle single-cell multiomic readouts reveal that cell heterogeneity influences lipid nanoparticle-mediated messenger RNA delivery. Nature Nanotechnology.

Researchers from the Georgia Institute of Technology and Emory University’s School of Medicine have developed a system that makes nanoparticle delivery to subsets of cells more predictable by combining DNA barcoding with a nanoparticle delivery system called single-cell nanoparticle targeting-sequencing (SENT-seq). Using SENT-seq, the investigators identified how different nanoparticles deliver DNA barcodes and mRNA into cells to affect the transcriptome and proteome with single cell resolution. [Read More]