New advances in nanotechnology grounded in physics, chemistry, and engineering are essential to modern cell and molecular biology research. In recent years, scientists have developed powerful tools to extensively categorize and functionally analyze the parts of cells, and we now know a great deal about how these intracellular structures operate. But biologists are still unable to answer many questions about molecular dynamics at the nanoscale. In order to build nanostructures and nanodevices that are compatible with living tissues and can safely operate inside the body for therapeutic purposes, these questions must be addressed.

Applying nanobiotechnology to molecular and cellular dynamics refers to highly specific biological intervention at the molecular scale. Bringing this perspective into the realm of nanoscience will enable researchers to manipulate individual genes and proteins for investigating complex biological functions in living cells, and ultimately for curing diseases. Because biological molecules and structures inside living cells are too small to be seen with conventional microscopes, research on the scale of nanometers will enable previously impossible feats. Tools in development at INBT will provide a better understanding of the signaling pathways that regulate embryonic development, cell differentiation, cell motility, and immune responses. 

Research challenges and long-term objectives include:

• visualizing entire signaling pathways inside cells in real-time
• placing biosensors, the size of a single molecule, into cells that can sense subcellular concentrations of enzymes and small molecules
• investigating the real-time visualization force-generation activity of a single motor protein
• organizing and altering single proteins to increase cell responses

Projects include development of the following:

• next-generation fluorescent reporters and nanoprobes to monitor single molecules in real time and in living cells
• structurally-based methods to develop proteins that can be locally activated and relocated through genetic means and/or external magnetic/optical/electric fields using micropatterned substrates or microneedles
• genetically-encoded biosensors and bioconjugated nanoparticles to image in real time and in living cells the dynamic conformational changes
• higher resolution live-cell imaging instruments, with the ambitious goal of reaching the new spatial resolution limit of 50 nanometers
• highly robust fluorescent proteins and quantum dot bioconjugates that are engineered to allow the visualization of multiple biochemical reactions and correlated events taking place simultaneously in a single living cell