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At GNF, we have been developing and implementing high throughput miniaturized assays and robotic systems to enable drug discovery for over 15 years. This presentation will review how our platform systems have adapted to and incorporated the latest scientific and technical advancements. Our flagship high throughput screening systems, capable of running hundreds of thousands of compounds per day against cellular or biochemical assays, continue to demonstrate their effectiveness. We have continued to expand the utility of GNF-built automation, as well as other commercially available technologies, to enable cost effective and rapid cell-based profiling of small molecules as well as biologics. In addition, this approach has allowed scientists to run primary cell assays on a scale not otherwise practical. Examples will include instruments and automation to greatly accelerate high-content phenotypic assays and flow cytometry. The latest advancements in reagent dispensing, detection and robotics will further the deployment of these technologies into areas such as highly multiplexed transcriptional readouts and Next Gen Sequencing.

Mammalian brains store and update quantitative internal variables. Primates and rodents, for example, have an internal sense of whether they are 1 or 10 meters away from a landmark and whether a ripe fruit is twice or four times as appetizing as a less ripe counterpart. Such quantitative internal signals are the basis of cognitive function, however, our understanding of how the brain stores and updates these variables remains fragmentary. In this talk, I will discuss imaging and perturbation experiments in tethered, walking Drosophila. The goal of these experiments is to determine how internal variables are calculated by the tiny Drosophila brain and how these variables influence behavior. Specifically, in the Drosophila central complex a set of heading neurons have been described, whose activity tracks the fly’s orientation, similar to head direction cells in rodents. However, the circuit architecture that gives rise to these orientation tracking properties remains largely unknown in any species. I will describe a set of clockwise- and counterclockwise-shifting neurons whose wiring and calcium dynamics provide a means to rotate the heading system’s angular estimate over time. Shifting neurons are required for the heading system to properly track the fly's movements in the dark, and, their stimulation induces a rotation of the heading signal in the expected direction and by the expected amount. The central features of this circuit are analogous to models proposed for head-direction cells in rodents and may thus inform how neural systems, in general, perform addition.