Feng Zhang used to think biology was all about animals and anatomy, but a seventh-grade enrichment program in molecular biology changed his mind. “I saw that biology is also about little molecular parts you can play with and put together in engineering ways,” he says. Now as a new member of the Department of Brain and Cognitive Sciences, the McGovern Institute for Brain Research, and the Broad Institute, Zhang is engineering nano-sized materials to change brain activity in animal models of psychiatric disease. “I’m using these tools to discover what goes wrong in brain circuits in these diseases, and to learn how to fix it,” he says.
If that sounds ambitious, consider that he co-developed a revolutionary technology called optogenetics, now used by neuroscientists worldwide, in his first lab rotation as a new Stanford graduate student with Karl Deisseroth in 2004. They decided to see if they could use the newly discovered channelrhodopsin, a protein made by green algae that opens a pore in cell membranes in response to light, to control the activity of neurons. As an undergraduate at Harvard, Zhang had studied how viruses enter cells, so he now engineered a virus to deliver the light-activated protein into specific sets of neurons in transgenic animals. Working with fellow graduate student Ed Boyden (now a fellow member of the McGovern Institute), he developed a mini-hardware system using lasers and fiber optics to precisely control the neurons expressing these proteins in living animals, turning them on and off with colored lights to study neural patterns involved in sleep and reward conditioning. “We can use this tool to see what the many different types of cells in the brain do and how they correlate with behavior,” Zhang says. “It’s a way to take apart a very complex brain.”
Then, as a junior fellow at Harvard, Zhang created another tool using other newly discovered proteins, TAL (transcription activator-like) effector proteins made by Xanthomonas bacteria. “These proteins manipulate the genome of the plants the bacteria live on,” he explains, “and we can engineer them to bind to any DNA sequence we want and modulate the expression of genes in specific types of neurons.”
Now at MIT, Zhang is using these tools in animal models of depression and schizophrenia to discover what changes result in psychiatric disease. For example, he wants to understand how environmental influences change the way genes are expressed in neural circuits in people genetically predisposed to depression. “We’re working with the Broad Institute to map the changes in the genome, and we’re applying optogenetics and gene transcription modulation to correct the errant patterns of gene activity to see if we can rescue the behavioral deficit. That could lead us to new targets for developing new treatments or cures.”
Zhang says he was attracted to MIT because of its sense of practicality. “The school wants to make something that translates into people’s lives,” he says. “It’s also very collaborative, and those interactions are important — because psychiatric diseases are not small problems.”