Genetically encodable optical technologies, such as fluorescent proteins and optogenetics, have revolutionized biomedical research by enabling observations and control of molecular processes in genetically engineered cells. However, these optical methods are fundamentally limited by the penetration depth of light in opaque biological tissues. George Lu's research aims to develop new genetically encodable agents that can communicate with deeply penetrant forms of energy, such as magnetic field and sound waves used in magnetic resonance imaging (MRI) and ultrasound imaging. These new technologies have the potential to enable functional tracking and precise control of therapeutic cells noninvasively in cell-based therapies.
Prior to joining Rice, Lu’s Ph.D. research at UC San Diego focused on membrane protein structural biology and the development of NMR spectroscopy. Motivated by applying the knowledge of protein structures to the engineering of proteins for novel biomedical applications, George Lu transitioned to his postdoctoral research on protein engineering in the laboratory of Dr. Mikhail Shapiro at Caltech, where he focused on a class of gas-filled hollow protein nanostructures called gas vesicles (GVs). Exploring the unique mechanical and material properties of these biogenic gas compartments, he led the projects to develop GVs as “erasable” MRI contrast agents and as the first genetically encodable optical coherence tomography (OCT) contrast agents. For these pioneering works, he was recognized as the Young Investigator of the Year by the World Molecular Imaging Society in 2018.
George Lu’s research at Rice, which is supported by the NIH Pathway to Independence (K99/R00) award and a $2 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT), will (i) explore the biophysical properties of GVs for novel therapeutic applications, (ii) pursue structure-based mechanism and design of GVs, and (iii) use synthetic biology to develop structural biology methods. These projects are built on a common pipeline of biochemistry, structure, design, and engineering of proteins, which will be established as the core expertise of the Laboratory for Structural Biomolecular Engineering.
Gas vesicles (GVs) are a class of gas-filled hollow protein nanostructures. They were evolved in certain photosynthetic microbes, and serve as their flotation devices in bodies of water. GVs are several hundreds of nanometers in size and made exclusively of proteins, which form a 2-nm-thick porous, amphipathic shell that allows gas to freely exchange but prevents the condensation of water vapor inside the nanostructures. Notably, the physical properties of GVs, including their size, shape, and critical collapse pressure are determined by their genetic sequence, and can vary significantly (often by more than an order of magnitude) among different species. In the past few years, the biomolecular engineering of GVs opened up a new frontier of noninvasive deep-tissue imaging of cellular function, such as being developed as the first reporter genes for ultrasound imaging, the erasable MRI contrast agents, and the first genetically encodable OCT contrast agents. In addition, GVs can potentially enable the manipulating and control of genetically engineered cells, such as through GV-based acoustic tweezer and cavitation.
The Laboratory for Structural Biomolecular Engineering will employ protein engineering, synthetic biology, chemical biology, and computational biology to understand the biochemistry and biophysics of these class of protein nanostructures, and to engineer novel biomedical applications based on their unique properties. Current research includes several interrelated directions: