Cell therapies have emerged as one of the most promising cancer treatments. However, they face a major hurdle, which is the lack of robust methods to functionally track these cells after they are infused to animal models or human patients.

Inspired by how the green fluorescent protein (GFP) revolutionized cellular imaging, we have recently developed agents that are genetically encodable similar to GFP but, instead of being imaged by light with a tissue penetration depth limited to ~ 1 mm, are imaged by ultrasound, magnetic resonance imaging (MRI), or optical coherence tomography (OCT) that reaches deep tissue. These agents are gas vesicles (GVs), hollow gas-filled protein nanostructures isol...

Read More

Cell therapies have emerged as one of the most promising cancer treatments. However, they face a major hurdle, which is the lack of robust methods to functionally track these cells after they are infused to animal models or human patients.

Inspired by how the green fluorescent protein (GFP) revolutionized cellular imaging, we have recently developed agents that are genetically encodable similar to GFP but, instead of being imaged by light with a tissue penetration depth limited to ~ 1 mm, are imaged by ultrasound, magnetic resonance imaging (MRI), or optical coherence tomography (OCT) that reaches deep tissue. These agents are gas vesicles (GVs), hollow gas-filled protein nanostructures isolated from buoyant photosynthetic microbes, that become visible in these imaging modalities due to their unique material and mechanical properties.

Here, I propose to develop the major next step in GV-based imaging, the multi-color imaging capability. Different species of GVs can be differentiated by their acoustic collapse pressures, which are genetically encoded properties of their shell proteins. By systematically engineer the shell protein, I aim to develop novel variants of GVs that span the “color spectrum” and can be simultaneously expressed as transgenes inside a cell. These new agents will then be used to enable the tracking of location and cellular signaling of therapeutic bacteria against metastatic melanoma.

If successful, this will pave the way towards future adoption of this general multi-color imaging paradigm to other therapeutic cells, especially genetically engineered T cells. My expertise in synthetic biology, protein structural biology, and molecular imaging makes me uniquely qualified to implement this research plan.

Additionally, the outstanding research environment within the Bioengineering department at Rice University, and the input from collaborators at MD Anderson Cancer Center, will be optimal for the success of the proposed aims.

Read Less