On Monday night, a presentation and panel discussion centered on the US’s BRAIN (Brain Research Through Advancing Innovative Neurotechnologies) Initiative (see IBO 4/15/13, 6/15/14). Launched in 2013, the BRAIN Initiative is a US public-private partnership to accelerate technology and application development for the study of the human brain. For FY17, the US presidential budget for the Project is $450 million. Run by the NIH, federal agencies involved in the Project are the DOE, DARPA (Defense Advanced Research Projects Agency), the NSF, IARPA (Intelligence Advanced Research Projects Activity) and the FDA.
The discussion looked at the history of the Initiative, currently funded projects and the future of neuroscience research in general. Chris Martin, PhD, of the Kavli Foundation, a private sector supporter of the BRAIN Initiative, announced the launch of BRAIN Initiative Alliance webpage (http://www.braininitiative.org/) to serve as a centralized information location for both the public and researchers for information regarding the BRAIN Project and similar projects worldwide. The site also includes a listing of grant opportunities.
Four researchers presented the results of research funded by BRAIN Initiative grants, highlighting the emphasis of the project on technology development and application. Among the techniques highlighted by the scientists discussing their research funded by the BRAIN Initiative was the use of single-cell RNA-Seq to characterize cell types in the brain; optogenetics to study dexterous behavior in mouse models; a human-wearable PET scanner, which allows for full head motion; and the mapping of the human neocortex using massively parallel single-cell analysis.
In the subsequent group discussion, Walter Koroshetz, MD, director of the NIH’s National Institute of Neurological Disorders and Stroke, noted that future investments by the BRAIN Initiative will emphasize technologies for working with non-model organisms. William Newsome, PhD, of Stanford University discussed the importance of theoretical approaches and statistics to understanding large data sets. Jim Deshler, PhD, deputy division director of the NSF’s Directorate for Biological Sciences/Division of Biological Infrastructure, told the audience that the NSF is working to coordinate the BRAIN Initiative with brain research worldwide such as the EU’s Brain Project (see IBO 1/31/13). Reflecting on lessons learned from other fields, the panel discussed the need for team (versus individual) science. Dr. Koroshetz noted the NIH is trying to advocate for such an approach.
As for the exhibit, venture-backed start-up Ultivue, whose original patents were licensed from the Wyss Institute at Harvard University and Caltech, was at the show, presenting its first commercial product, the Ultivue-2 kit for super resolution microscopy. The Ultivue-2 kit is based on the DNA-PAINT (Point Accumulation for Imaging in Nanoscale Topography) technology for single-molecule localization. DNA-PAINT utilizes short complementary DNA strands, one attached to an antibody and its complement to a fluorophore. Transient hybridization of these short strands in combination with optical sectioning (i.e., TIRF, SPIM illumination) allows for the “blinking” characteristic of single-molecule localization techniques. However, in contrast to the use of dye-labeled antibodies, the transient bond allows for single-channel imaging of multiple colors sequentially using the same dye and immunity to photobleaching. Demonstrated resolution is as low as 20 nm in cells.
The technology also alleviates pain points in super resolution by requiring lower laser power, and less strenuous sample and buffer preparation. Launched this summer, the Ultivue-2 is a two-plex secondary antibody-based kit for an average of 25 two-color experiments in super resolution. It is priced at $750 and available from Ultivue’s website. In addition, the DNA strands can be lengthened to accommodate stable binding and dehybridized at any time with a proprietary buffer, allowing for high multiplexing at standard resolution microscopy in cell and tissue samples. Ultivue also showcased its first secondary antibody-based kit, available for early adopters under a material transfer agreement, which enables imaging of up to five colors in cells, including the DAPI fluorescent stain.
Super resolution microscopy was definitely a theme at the show, as all major vendors were represented. At the show, Nikon Instruments launched the ECLIPSE Ti2 Inverted Research Microscope. The system features a 25 mm field of view (fov), compared to 18 mm on the ECLIPSE Ti. The larger fov allows the system to take greater advantage of large-format CMOS cameras. Consequently, the system enables higher data throughput. High throughput is also enabled by hardware-triggering, in which the camera exposure signal triggers the activity of other devices instead of the software processing.
Also emphasizing speed was ZEISS with its new Airy Scan Fast confocal laser scanning microscopy system. Based on a new illumination shaping approach, the system features an increased speed of 20–50 frames per second and improved signal of noise, compared to the Airy Scan. The company claims a four-times increase in acquisition speed.
At the show, Bruker launched the Ultima NeuraLight 3D module for its Ultima Multiphoton Microscopes, designed for optogenetic applications. Optogenetics is the control of neurons through light by targeting specific proteins. The Ultima NeuraLight 3D combines 3-D optical stimulation and multiphoton imaging, resulting in a 3-D laser hologram based on multiple stimulation points. Special software allows for fast switching times (300–500 Hz) to capture 3-D activation patterns.
Next year’s conference will be held November 11–15 in Washington, DC.
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Authored by Tanya Samazan