We use recycled products every day. Money, for example, goes on a circular journey from our hands to banks and back again. Once paper money is too worn to be used, banks send it to be destroyed. A similar microscopic waste system is present in our brains, in which nervous system cells called neurons trade chemical messengers and remove the carriers they travel in when they become defective.
Now two Johns Hopkins Medicine researchers, Takanari Inoue, Ph.D., and Shigeki Watanabe, Ph.D., have received $150,000 from the Chan Zuckerberg Initiative to study ways to make this waste management process more efficient. The research could eventually help scientists develop treatments for neurodegenerative diseases such as Parkinson’s disease, Huntington’s disease and dementia, conditions that are marked by faulty recycling of the vesicles that carry chemical messengers, or neurotransmitters.
Inoue and Watanabe study cell signaling and plasticity, which allow cells to communicate and adjust to changing activity. Together, their labs will team up to understand how brain cells signal to the brain’s immune cells for garbage removal.
Neurons are, famously, uniquely shaped cells. The cell body is surrounded by short projections, known as dendrites, and it sprouts one long branch, the axon, which forks off into smaller, short branches called axon terminals. At the junction between two neurons, otherwise known as the synapse, vesicles carry neurotransmitters out of one neuron and onto another. This happens rapidly, in milliseconds, but it takes days for newly made vesicles to travel the whole length of a neuron, from the cell body to its axon terminals, causing neurons to recycle vesicles so that enough are present at the synapse.
While vesicles and vesicle proteins need to be recycled within synapses, the faulty parts need to be discarded. Some defective parts are disposed of at the synapse, but others must be driven back to the cell body for disposal.
The brain’s waste management system works less effectively as humans age and in those with certain genetic mutations. Inoue and Watanabe aim to understand how the waste management issue is communicated to the surrounding cells and develop a synthetic system to clear out the garbage from the nerve cells on demand.
In addition to Inoue and Watanabe’s award, the Chan Zuckerberg Initiative has funded 30 pairs of researchers from around the globe in its Neurodegeneration Collaborative Pairs pilot projects, an initiative to foster collaboration among scientists working to treat neurodegenerative diseases. The current award is part of phase 1 of the initiative. If selected for phase 2, the pair will potentially be awarded an additional $1.2 million.
According to Watanabe, the collaboration will enable them to capitalize on their research techniques and encourage an open exchange of ideas. “In a lab, members share their ideas, but because they use similar techniques and address related research questions, they tend to approach scientific questions in a similar fashion,” says Watanabe. “However, by talking to people in other labs, new ideas can arise.” Inoue explains that “the very ideas of the grant were, in part, born from a joint lab retreat in May last year.”
The partnership will also contribute to diversity and inclusion efforts in the scientific community — both labs are involved in research programs for underrepresented minorities. As part of these programs, the pair plan to develop joint summer projects that enable students to work between both labs.
