Bussell, R. | bioRxiv Science

bioRxiv2020

Acoustogenetic Control of CAR T Cells via Focused Ultrasound

Optogenetics can control specific molecular events in living systems, but the penetration depth of light is typically limited at hundreds of micrometers. Focused ultrasound (FUS), on the other hand, can deliver energy safely and noninvasively into tissues at depths of centimeters. Here we have developed an acoustogenetic approach using short-pulsed FUS to remotely and directly control the genetics and cellular functions of engineered mammalian cells for therapeutic purposes. We applied this acoustogenetic approach to control chimeric antigen receptor (CAR) T cells with high spatiotemporal precision, aiming to mitigate the potentially lethal "on-target off-tumor" effects of CAR T cell therapy. We first verified the controllability of our acoustogenetic CAR T cells in recognizing and killing tumor cells in vitro, and then applied this approach in vivo to suppress tumor growth of both lymphoma and prostate cancers. The results indicate that FUS-based acoustogenetics can allow the noninvasive and remote activation, without any exogenous cofactor, of different types of CAR T cells for cancer therapeutics.

bioengineering↗

bioRxiv2019

Chemical Impacts of the Microbiome Across Scales Reveal Novel Conjugated Bile Acids

A mosaic of cross-phyla chemical interactions occurs between all metazoans and their microbiomes. In humans, the gut harbors the heaviest microbial load, but many organs, particularly those with a mucosal surface, associate with highly adapted and evolved microbial consortia1. The microbial residents within these organ systems are increasingly well characterized, yielding a good understanding of human microbiome composition, but we have yet to elucidate the full chemical impact the microbiome exerts on an animal and the breadth of the chemical diversity it contributes2. A number of molecular families are known to be shaped by the microbiome including short-chain fatty acids, indoles, aromatic amino acid metabolites, complex polysaccharides, and host lipids; such as sphingolipids and bile acids3-11. These metabolites profoundly affect host physiology and are being explored for their roles in both health and disease. Considering the diversity of the human microbiome, numbering over 40,000 operational taxonomic units12, a plethora of molecular diversity remains to be discovered. Here, we use unique mass spectrometry informatics approaches and data mapping onto a murine 3D-model13-15 to provide an untargeted assessment of the chemical diversity between germ-free (GF) and colonized mice (specific-pathogen free, SPF), and report the finding of novel bile acids produced by the microbiome in both mice and humans that have evaded characterization despite 170 years of research on bile acid chemistry16.

microbiology↗