Molecular Engineering for Non-Invasive Imaging and Control of Biological Systems

Many important biological processes occur deep inside living organisms. Their study requires technologies to image and manipulate cellular and molecular function non-invasively. To develop such technologies, we pursue fundamental advances at the interface of molecular and cellular engineering with various forms of physical energy: magnetic, mechanical, thermal and chemical. Our work takes advantage of naturally evolved biological structures with unique physical properties, which we use as starting points for engineering. Examples of current research include:

Genetically Encoded Reporters for Ultrasound
We are developing the first genetically encoded and engineered imaging agents for ultrasound based on gas vesicles (GVs), a unique class of hollow protein nanostructures from buoyant microbes. Current work is focused on understanding and engineering the acoustic properties and in vivo interactions of GVs as targeted molecular imaging agents, and using them as reporter genes in cell-based therapeutics and diagnostics.
Collaborators: Stuart Foster (U. Toronto), Dennis Kochmann (Caltech), Mickael Tanter (INSERM, Paris), Richard Andersen (Caltech)

Genetically Encoded Reporters, Devices and Basic Mechanisms of MRI
We are developing next-generation genetically encoded reporters and sensors for MRI. For some of this work, we engineer paramagnetic proteins to produce contrast changes in T1 and T2 weighted MRI in response to chemical metabolites and signals such as neurotransmitters or ATP. In addition, we are developing new classes of genetically encoded reporters that operate through novel contrast mechanisms. For example, we are developing the first MRI reporter genes for hyperpolarized xenon MRI and diffusion-weighted MRI. Furthermore, we are studying the fundamental mechanisms of MRI contrast using nitrogen vacancy diamond magnetometry.
Funding: Burroughs Wellcome Fund, Dana Foundation, W.M. Keck Foundation, Human Frontiers Science Foundation
Collaborators: Leif Schroeder (Leibniz Institut, Berlin), Ron Walsworth (Harvard), Azita Emami (Caltech)

Ultrasonic and Thermal Modulation of Biological Systems
We are interested in controlling cellular agents such as engineered microbes remotely within the body. For eample, we have engineered tunable thermal bioswitches that allow us to control gene expression in engineered microbes using ultrasound with millimeter precision. In addition, ultrasound has been shown to stimulate and inhibit neural activity in animals and humans, but the mechanisms of this neuromodulation are not well understood. We are studying these mechanisms at the biophysical, molecular, cellular, circuit and whole-brain levels. Previously, we used similar approaches to determine the mechanisms of infrared neural stimulation.
Funding: NIH (BRAIN Initiative, NIMH), DARPA
Collaborators: Doris Tsao (Caltech)

Additional support acknowledgements: Heritage Medical Research Institute, Jacobs Institute for Molecular Engineering in Medicine, Weston Havens Foundation, Sontag Foundation, Pew Fellowship in the Biomedical Sciences, Packard Fellowship for Science and Engineering

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