By Nicholas Weiler
The Wu Tsai Neurosciences Institute has awarded its fourth round of seed grants to five interdisciplinary teams of researchers studying important questions in neuroscience.
The seed grants, which the institute has awarded every two years since 2015, are intended to foster collaborations between small teams of researchers from different backgrounds and disciplines, to allow them to pilot novel research ideas that may be risky but have the potential to dramatically impact the field.
This year, the institute is awarding grants to researchers spanning nine Stanford departments, from pediatrics to electrical engineering. The funded projects aim to address important questions in the neural drivers of diseases of early brain development and age-related neurodegeneration; to explore whether a sense of touch helps nerve fibers make synaptic connections; and to develop transformative new brain recording and stimulation technologies.
“We received an overwhelming number of outstanding, innovative proposals this year, but these teams rose to the top because of their potential to explore novel hypotheses and produce powerful new technologies that could change the way we conceptualize brain function,” said Robert Malenka, MD, PhD, the Nancy Friend Pritzker Professor of Psychiatry and Behavioral Sciences, who chaired Wu Tsai Neuro’s Seed Grants selection committee.
This team aims to develop a noninvasive technology for on-demand control of targeted cell populations throughout the brains of live mice. Optogenetics is a powerful technique for controlling the activity of genetically-defined brain cells using light, but it is challenging to deliver the light deep into the brain or to dynamically shift stimulation between different brain regions. The proposed research will employ mechanoluminescent nanoparticles that can be made to produce light anywhere in the brain using focused ultrasound. The researchers will test the system’s ability to screen multiple brain regions for their contributions to addictive drug seeking behavior.
This team aims to understand the role of mechanical force on synapse formation in the wiring of brain circuits during development. A family of synaptic molecules called latrophilins are known to play an important role in synapse formation, but the mechanism of their contribution is unknown. The proposed research will test the innovative hypothesis that latrophilins mediate molecular-scale mechanical signals to sculpt synapse formation and will shed light on how latrophilin signaling regulates synapse formation during brain development and how it may go awry in neuropsychiatric disease.
This team aims to reveal how the failure of mitochondrial quality control during aging contributes to nerve cell death in Parkinson’s disease — and how this process could be reversed to treat the disease. Little is known about the molecular drivers of age-related mitochondrial dysfunction and the toxic factors the cell’s power plants produce when they fail. The researchers plan to comprehensively map this gene network in PD-afflicted cells for the first time using cutting-edge CRISPR DNA-targeting technology. If successful, the project could identify novel targets for the first disease-modifying therapies for PD.
Ada Poon, Electrical Engineering
Shan Wang, Electrical Engineering
Paul George, Neurology and Neurological Sciences
This team aims to engineer a magnetic sensor and stimulator of neuronal activity that could complement or replace standard microelectrodes in experimental and clinical neuroscience. By recording magnetic fields, such a device could directly record the electrical currents within neurons, and do so through a protective coating designed to minimize the inflammatory scarring that limits the useful lifetime of conventional micro-electrodes. The proposed device would take advantage of the team’s expertise in cutting edge circuit design and fabrication techniques, and the development of novel laboratory testing platforms to systematically validate the sensor.
Carla Shatz, Biology, Neurobiology
Anca Pasca, Pediatrics
Michelle Drews, School of Medicine, Neurosciences
This team aims to examine what happens when the developing brain experiences a viral infection, which has been linked to neurodevelopmental disorders such as schizophrenia and autism. The research centers on a family of molecules called MHCI, which plays important roles in both immune responses to infection and in synapse formation during brain development. This researchers will study what happens when the brain and immune system collide, using innovative human brain organoid models and fetal brain samples to examine how virus-associated interferons affect MHCI levels as well as synapse density and function.