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Swanson, R.

Publications and source records attributed to Swanson, R..

4 recordsLinked to original sources

Imaging high-frequency voltage dynamics in multiple neuron classes of behaving mammals

Fluorescent genetically encoded voltage indicators report transmembrane potentials of targeted cell-types. However, voltage-imaging instrumentation has lacked the sensitivity to track spontaneous or evoked high-frequency voltage oscillations in neural populations. Here we describe two complementary TEMPO voltage-sensing technologies that capture neural oscillations up to [~]100 Hz. Fiber-optic TEMPO achieves [~]10-fold greater sensitivity than prior photometry systems, allows hour-long recordings, and monitors two neuron-classes per fiber-optic probe in freely moving mice. With it, we uncovered cross-frequency-coupled theta- and gamma-range oscillations and characterized excitatory-inhibitory neural dynamics during hippocampal ripples and visual cortical processing. The TEMPO mesoscope images voltage activity in two cell-classes across a [~]8-mm-wide field-of-view in head-fixed animals. In awake mice, it revealed sensory-evoked excitatory-inhibitory neural interactions and traveling gamma and 3-7 Hz waves in the visual cortex, and previously unreported propagation directions for hippocampal theta and beta waves. These technologies have widespread applications probing diverse oscillations and neuron-type interactions in healthy and diseased brains.

neuroscience↗

De novo design of ACE2 protein decoys to neutralize SARS-CoV-2

There is an urgent need for the ability to rapidly develop effective countermeasures for emerging biological threats, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a generalized computational design strategy to rapidly engineer de novo proteins that precisely recapitulate the protein surface targeted by biological agents, like viruses, to gain entry into cells. The designed proteins act as decoys that block cellular entry and aim to be resilient to viral mutational escape. Using our novel platform, in less than ten weeks, we engineered, validated, and optimized de novo protein decoys of human angiotensin-converting enzyme 2 (hACE2), the membrane-associated protein that SARS-CoV-2 exploits to infect cells. Our optimized designs are hyperstable de novo proteins ([~]18-37 kDa), have high affinity for the SARS-CoV-2 receptor binding domain (RBD) and can potently inhibit the virus infection and replication in vitro. Future refinements to our strategy can enable the rapid development of other therapeutic de novo protein decoys, not limited to neutralizing viruses, but to combat any agent that explicitly interacts with cell surface proteins to cause disease.

biochemistry↗

VipariNama: RNA vectors to rapidly reprogram plant morphology and metabolism

Synthetic transcription factors have great promise as tools to explore biological processes. By allowing precise alterations in gene expression, they can help elucidate relationships between gene expression and plant morphology or metabolism. However, the years-long timescales, high cost, and technical skill associated with plant transformation have dramatically slowed their use. In this work, we developed a new platform technology called VipariNama (ViN) in which RNA vectors are used to rapidly deploy synthetic transcription factors and reprogram gene expression in planta. We demonstrate how ViN vectors can direct activation or repression of multiple genes, systemically and persistently over several weeks, and in multiple plant species. We also show how this transcriptional reprogramming can create predictable changes to metabolic and morphological phenotypes in the model plants Nicotiana benthamiana and Arabidopsis thaliana in a matter of weeks. Finally, we show how a model of gibberellin signaling can guide ViN vector-based reprogramming to rapidly engineer plant size in both model species as well as the crop Solanum lycopersicum (tomato). In summary, using VipariNama accelerates the timeline for generating phenotypes from over a year to just a few weeks, providing an attractive alternative to transgenesis for synthetic transcription factor-enabled hypothesis testing and crop engineering.

plant biology↗

Novel feeding and mating behaviors of a population of nautiluses, Nautilus belauensis, in Palau

The nautiloid lineage extends back nearly 500 million years but today, is represented by only two living genera, Nautilus and Allonautilus. Behavioral observations of these living nautiluses have improved our understanding of how nautiloids, and ammonoids, behaved and interacted in their environment. These behaviors may also help to inform conservation practices. Here, we describe feeding and mating behaviors in wild nautiluses not reported from any other population. In Palau, Nautilus belauensis was observed actively preying on a large, living crab (Chaceon sp.) and performing courtship-like behaviors prior to mating. These behaviors occurred across multiple nights and from different nautiluses, suggesting that the behaviors are characteristic of at least a subset of the population, if not the entire population. Perhaps the behaviors exhibited by the Palauan nautiluses are an outlier and simply a localized characteristic of a far-removed population. Or, perhaps these apparent abnormal behaviors of Palauan nautiluses are what all nautiluses across the Indo-Pacific should be exhibiting. If the latter explanation is correct, we can start to address the potential causes of the behavioral differences, such as population size, habitat type, and prey availability. In either case, this apparent behavioral plasticity may have also been a reason that the nautiloid lineage has been able to survive throughout millions of years of environmental changes. Today, these behavioral observations could prove to be a valuable conservation tool to protect species and environments, especially in the deep-sea ecosystem the nautiluses inhabit.

zoology↗