Abstract - Brenda Bloodgood

The brain’s capacity to learn from experience requires the conversion of transient brain activity into long-lasting changes in neural circuitry. Inducible transcription factors (ITFs) are uniquely poised to translate millisecond signals into persistent changes, but their specific functions in learning are still being elucidated. We propose the development of a new toolkit that enables the visualization and manipulation of endogenous ITFs in individual neurons, in real time, and in behaving animals. Our strategy utilizes molecular scaffolds, engineered through synthetic affinity maturation of nanobodies, which specifically bind to an endogenous ITF. The scaffold will be fused to a fluorophore and/or transcriptional modifier, allowing users to visualize endogenous ITFs and dynamically manipulate transcription. A degradation signal will be incorporated into the nanobody. Consequently, the nanobody can be constitutively expressed and degraded. When a neuron expresses the target ITF however, the ITF-nanobody interaction will stabilize the complex. We envision our transcriptional reporters will have a transformative impact on the broader community’s ability to investigate mechanisms that underlie stable and plastic representations in the brain and will open new areas of research, akin to the leap in understanding that has been facilitated by the development and use of genetically encoded calcium indicators.

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AWARDS

Principal Investigator Institution Title Abstract
Andersen, Richard California Institute of Technology Engineering Artificial Sensation View
Andrews, Anne University of California, Los Angeles Nanoscale Neurotransmitter Sensors View
Bloodgood, Brenda University of California San Diego A novel toolkit for visualizing and manipulating activity-induced transcription in living brain. View
Chaumeil, Myriam University of California, San Francisco In vivo metabolic imaging of neuroinflammation using hyperpolarized 13C View
Cleary, Michael University of California, Merced Capturing physiological maps of neural gene expression View
Cohen, Bruce University of California, Lawrence Berkeley National Laboratory Nano-optogenetic control of neuronal firing with targeted nanocrystals View
Dai, Hongjie Stanford University  Deep brain imaging of single neurons in the second near-infrared optical window View
Hall, Drew University of California, San Diego Magnetic Monitoring of Neural Activity using Magnetoresistive Nanosensors View
Krubitzer, Leah University of California, Davis An integrated system to monitor, image, and regulate neural activity View
Kubby, Joel University of California, Santa Cruz Three-Photon Microscopy with Adaptive Optics for Deep Tissue Brain Activity Imaging View
Melosh, Nicholas Stanford University Parallel Solid State Intracellular Patch-Clamping with Biomimetic Probes View
Park, B. Hyle University of California, Riverside  Label-free 4D optical detection of neural activity View
Portera-Cailliau, Carlos University of California, Los Angeles High-speed interrogation of network activity with frequency domain multiplexing View
Shanechi, Maryam University of Southern California Control-Theoretic Neuroprosthetic Design Using Electrocorticography Signals View
Smith, Will University of California, Santa Barbara Whole brain imaging in a primative chordate View
Wood, Marcelo University of California, Irvine Epigenetic PET tracer for cross-species investigation of age-related memory dysfunction View