By Lesley Colgan, MPFI Research Scientist
The complex network of neurons that carry electrical signals through pathways in our brain allow us to see, breathe, learn and think. However, packed inside each neuron are the real heroes of the brain, tens of thousands of tiny molecular machines that work together in their own complex networks to generate and modulate our brain signals. Critical to brain function, these proteins are also the target of pharmaceuticals. Therefore, understanding their roles and complex interactions is crucial to developing effective therapies for brain disorders. It is also an immense challenge for neuroscientists.
I like to think of protein networks as one of those viral, epic marble runs you can find on YouTube, only much more complex. The energy is passed from that first rolling marble at the start by interacting with other marbles, blocks, balls, and magnets, sometimes in surprising ways, until the goal is reached. Through close observation, we can understand how the marbles traveled from start to finish.
When a neuron receives information, it is the force that sets that first marble rolling. This activated protein sets off a complex chain of events involving hundreds of other proteins that interact and modify the signal, similar to the blocks, balls, and magnets that interact with the marble. How can scientists understand these events, however, without seeing each intricate piece of the marble run?
Until recently, neuroscientists’ tools to study protein cascades were blunt. We could disrupt one of the proteins-either by deleting it or impairing its function, and in doing so, interrupt the signal. Just as removing a block from the marble run would cause the marble to fall. While this told scientists that the specific protein was essential to achieving the goal, it didn’t explain its precise role. It couldn’t answer how, when, and where we should activate this protein to repair neuronal dysfunction in disease. Suppose, however, that scientists could see precisely how the protein cascade worked by visualizing all of its parts. In that case, there might be hope to answer these questions.
Biosensors are tools that move neuroscientists toward that goal. In simple terms, a biosensor allows scientists to detect a biological change in a living neuron. Like putting a light on a specific piece of the marble maze that flashes when hit by the marble, a biosensor converts protein activity into something we can see and measure. In neuroscience, this is usually light, or more specifically, fluorescence. Scientists can then use a microscope to detect the fluorescence change and thus ‘see’ the protein activity in a functioning neuron.
Scientists like Dr. Ryohei Yasuda, one of the scientific directors at MPFI, are developing and using biosensors to determine the intricate marble maze that mediates neuroplasticity. Of course, this takes time as each biosensor only reveals one piece of the maze. With enough pieces, however, we may be able to understand how these thousands of miniature machines work together in each of our neurons to allow us to learn. More importantly, it may lead us to clues on repairing neuron function in mental health disorders and neurodegenerative disease.