The Scripps Research Institute

Neurosciences Research Foundation, Inc.

Other

Neuroscience Research Foundation, Inc.

Gerald M Edelman

Vincent P Mauro

Jeffrey L Krichmar

Wei Zhou

Stephen A Chappell

Geoffrey Owens

Douglas A Nitz

Jeffrey L McKinstry

Douglas Alan Moore

Donald Hutson

James Andrew Snook

Bruce A Cunningham

Leslie Krushel

Frederick S Jones

Robyn Meech

Jason G Fleischer

Kathryn L Crossin

Giulio Tononi

George N Reeke, Jr

Botond Szatmáry

Jason K Pinkstaff

Olaf Sporns

Botond Szatmary

Luke Burman

Anil K Seth

Provided herein are methods for stable integration and/or expression of one or more recombinant polynucleotides in a host cell. The recombinant polynucleotides are typically integrated into the host genome at some native chromosomal integration sites. The integration can be mediated by homologous recombination or by using a hybrid recombinase targeting the specific chromosomal locations. The native chromosomal integration sites in the host cells, which support stable integration and strong transcription activities of foreign genes, are present within or adjacent to specific genes in the CHO genome, the ankyrin 2 gene (Ank2), cleavage and polydenylation specific factor 4 gene (Cpsf4), C-Mos gene, and Nephrocystin-1/Mal gene. Also provided are methods and nucleic acid molecules for inserting site-specific recombination sequences (chromosomal landing pads) into these specific chromosomal locations, engineered host cells containing chromosomal landing pads, methods and compositions (e.g., kits) therefore.

Chromosomal landing pads and related uses

A translation enhancer-driven positive feedback vector system is disclosed which is designed to facilitate identification of a Translational Enhancer Element (TEE) and to provide a means for overexpression of gene products. The system exploits both transcriptional and translational approaches to control the expression levels of genes and/or gene products. Methods are also disclosed for screening libraries of random nucleotide sequences to identify translational elements and for overproduction of proteins, which have uses in both research and industrial environments.

Translational enhancer-element dependent vector systems

Provided herein is a synthetic or isolated polynucleotide encoding a mammalian 18S rRNA that is resistant to pactamycin. The pactamycin-resistance is conferred by one or more single residue substitutions in the 18S rRNA sequence; a fragment thereof harboring said substitutions; a complementary sequence thereto; or a substantially identical sequence of the foregoing. Related systems, methods and kits are also described.

Ribosomal polynucleotides and related expression systems

Translation enhancer-element dependent vector systems

Described herein are rules to modify natural mRNAs or to engineer synthetic mRNAs to increase their translation efficiencies. These rules describe modifications to mRNA coding and 3' UTR sequences intended to enhance protein synthesis by: 1) decreasing ribosomal diversion via AUG or non-canonical initiation codons in coding sequences, and/or 2) by evading miRNA-mediated down-regulation by eliminating one or more miRNA binding sites in coding sequences.

Reengineering mRNA primary structure for enhanced protein production

Provided are mRNA translational enhancer elements (TEEs), e.g., SEQ ID NOs:1-35. Also provided are translational enhancer polynucleotides that comprise one or more of the specific TEEs exemplified herein or their variants, homologs or functional derivatives. Further provided are expression vectors comprising such TEEs or translational enhancer polynucleotides, as well as host cells and expression systems that harbor such vectors.

Compositions and methods related to mRNA translational enhancer elements

A brain-based device (BBD) for moving in a real-world environment has sensors that provide data about the environment, actuators to move the BBD, and a hybrid controller which includes a neural controller having a simulated nervous system being a model of selected areas of the human brain and a non-neural controller based on a computational algorithmic network. The neural controller and non-neural controller interact with one another to control movement of the BBD.

Hybrid control device

A brain-based device (BBD) having a physical mobile device NOMAD controlling and under control by a simulated nervous system. The simulated nervous system is based on an intricate anatomy and physiology of the hippocampus and its surrounding neuronal regions including the cortex. The BBD integrates spatial signals from numerous objects in time and provides flexible navigation solutions to aid in the exploration of unknown environments. As NOMAD navigates in its real world environment, the hippocampus of the simulated nervous system organizes multi-modal input information received from sensors on NOMAD over timescales and uses this organization for the development of spatial and episodic memories necessary for navigation.

Mobile brain-based device having a simulated nervous system based on the hippocampus

A mobile brain-based device (BBD) includes a mobile platform with sensors and effectors, which is guided by a simulated nervous system that is an analogue of the cerebellar areas of the brain used for predictive motor control to determine interaction with a real-world environment. The simulated nervous system has neural areas including precerebellum nuclei (PN), Purkinje cells (PC), deep cerebellar nuclei (DCN) and an inferior olive (IO) for predicting turn and velocity control of the BBD during movement in a real-world environment. The BBD undergoes training and testing, and the simulated nervous system learns and performs control functions, based on a delayed eligibility trace learning rule.

Brain-based device having a cerebellar model for predictive motor control

A mobile brain-based device BBD includes a mobile base equipped with sensors and effectors (Neurally Organized Mobile Adaptive Device or NOMAD), which is guided by a simulated nervous system that is an analogue of cortical and sub-cortical areas of the brain required for visual processing, decision-making, reward, and motor responses. These simulated cortical and sub-cortical areas are reentrantly connected and each area contains neuronal units representing both the mean activity level and the relative timing of the activity of groups of neurons. The brain-based device BBD learns to discriminate among multiple objects with shared visual features, and associated 'target' objects with innately preferred auditory cues. Globally distributed neuronal circuits that correspond to distinct objects in the visual field of NOMADare activated. These circuits, which are constrained by a reentrant neuroanatomy and modulated by behavior and synaptic plasticity, result in successful discrimination of objects. The brain-based device BBD is moveable, in a rich real-world environment involving continual changes in the size and location of visual stimuli due to self-generated or autonomous, movement, and shows that reentrant connectivity and dynamic synchronization provide an effective mechanism for binding the features of visual objects so as to reorganize object features such as color, shape and motion while distinguishing distinct objects in the environment.

Mobile brain-based device for use in a real world environment

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La Jolla, CA, United States of America

Gerald M Edelman