The breadth of genomic diversity found among organisms in nature allows populations to adapt to diverse environments1,2. However, genomic diversity is difficult to generate in the laboratory and new phenotypes do not easily arise on practical timescales3. Although in vitro and directed evolution methods4–9 have created genetic variants with usefully altered phenotypes, these methods are limited to laborious and serial manipulation of single genes and are not used for parallel and continuous directed evolution of gene networks or genomes. Here, we describe multiplex automated genome engineering (MAGE) for large-scale programming and evolution of cells. MAGE simultaneously targets many locations on the chromosome for modification in a single cell or across a population of cells, thus producing combinatorial genomic diversity. Because the process is cyclical and scalable, we constructed prototype devices that automate the MAGE technology to facilitate rapid and continuous generation of a diverse set of genetic changes (mismatches, insertions, deletions). We applied MAGE to optimize the 1-deoxy-d-xylulose-5-phosphate (DXP) biosynthesis pathway in Escherichia coli to overproduce the industrially important isoprenoid lycopene. Twenty-four genetic components in the DXP pathway were modified simultaneously using a complex pool of synthetic DNA, creating over 4.3 billion combinatorial genomic variants per day. We isolated variants with more than fivefold increase in lycopene production within 3 days, a significant improvement over existing metabolic engineering techniques. Our multiplex approach embraces engineering in the context of evolution by expediting the design and evolution of organisms with new and improved properties.

Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light–induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience.

Whole-cell patch clamp electrophysiology of neurons is a gold standard technique for high-fidelity analysis of the biophysical mechanisms of neural computation and pathology but it requires great skill to perform. We have developed a robot that automatically performs patch clamping in vivo, algorithmically detecting cells by analyzing the temporal sequence of electrode impedance changes. We demonstrate good yield, throughput, and quality of automated intracellular recording in mouse cortex and hippocampus.

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Science and Technology, both in mechanical engineering. Since joining James Madison University, Nagel has helped to develop and teach the six course engineering design sequence which represents the spine of the curriculum for the Department of Engineering. The research and teaching interests of Dr. Nagel tend to revolve around engineering design and engineering design education, and in particular, the design conceptualization phase of the design process. He has performed research with the US Army Chemical Corps, General Motors Research and Development Center, and the US Air Force Academy, and he has received grants from the NSF, the EPA, and General Motors Corporation. Dr. Julie S Linsey, Georgia Institute of TechnologyDr. Julie S. Linsey is an Assistant Professor in the George W. Woodruff School of Mechanical Engineering at the Georgia Institute of Technological. Dr. Linsey received her Ph.D. in Mechanical Engineering at The University of Texas. Her research area is design cognition including systematic methods and tools for innovative design with a particular focus on concept generation and design-by-analogy. Her research seeks to understand designers' cognitive processes with the goal of creating better tools and approaches to enhance engineering design. She has authored over 100 technical publications including twenty-three journal papers, five book chapters, and she holds two patents. A Review of University Maker Spaces IntroductionAs society continues to progress in a globalized world, the necessity for more and better engineers is increasingly apparent. The engineer of the future needs to be able to harness creativity and innovation in order to stay competitive and relevant in an economy with ever growing needs.1 It is therefore the responsibility of the university to cultivate and grow these skills in their students. It has been seen, though, that the undergraduate curriculum lends itself to diminishing creativity in students.2 As such, there is opportunity for improvement in the undergraduate experience in order to not only alleviate this effect, but to also improve on vital engineering skills that are currently underdeveloped in graduating engineers. According to the creators of the Conceive-Design-Implement-Operate initiative (CDIO), skills beyond strictly technical knowledge such as interpersonal skills and critical thinking are in high demand in industry. 3,4 This is supported by the recently released ASEE Transforming Undergraduate Education in Engineering (TUEE) Phase I report.5 Fostering these skills is, however, no easy feat in the already tightly packed engineering curriculum. The current system has a heavy emphasis on theory and mathematical modeling as opposed to a more practice based curricula, which was the standard engineering education approach until the modern approach gained favor in a shift that occurred between 1935 and 1965.6 As a result of this shift, many engineering students do not spend much of their time engaged in actual design and build processes until late in their degree pr...