Five Questions for Feng Zhang
Core faculty member Feng Zhang, who joined the Broad in 2011, has quickly earned a reputation as one of the brightest young scientists working today. His research on optogenetics and genome engineering earned him a spot in this year’s “Brilliant 10,” Popular Science magazine's annual list of the most promising scientific innovators. He was also recognized last month by MIT Technology Review, which named him as one of their “35 Innovators Under 35” for 2013.
In this edition of “Five Questions,” Zhang, who is also an assistant professor at MIT and a principal investigator at the McGovern Institute for Brain Research at MIT, talks about his research, the excitement it has generated, and where he hopes his work may lead him.
Q1: Your lab is remarkably prolific. What is the primary focus of your research?
FZ: We’re looking at how the cells’ molecular machinery works and, to do that, we need new tools that allow us to have precise control over the biological activities happening inside the cell. My lab mainly focuses on developing tools that can help us understand how the genome works and how it influences the activity of brain cells to help organisms carry out complex functions. We are also looking at what goes wrong in these systems to cause disease.
Photo by Len Rubenstein
Q2: Can you describe the different lines of research that your lab pursues, and how they relate to each other?
FZ: Understanding how the brain works is one of my main interests. Two different lines of research – optogenetics and genome engineering – are helping my lab do that.
Optogenetics allows us to use light to control specific neurons, and thus control when and how information is sent from one brain cell to another. It’s really unique in the sense that you can specifically control the activity of a subset of cells in the brain without affecting nearby cells. This allows you to send information to the brain and see how it gets processed, so you can start to understand signaling in the brain.
Genome engineering looks at the brain from a different perspective. Using genome engineering or genome editing, we can change the actual DNA letters in the genome to understand which genes are involved in what function, and which genetic mutations are involved in a specific disease.
Q3: You were the senior author of a paper that came out just last week in Cell. Can you tell us a little bit about it?
FZ: The Cell paper builds on previous work that we did developing a new genome engineering system called CRISPR. One of the applications of CRISPR is to make very precise changes in the genome so that you can ask questions like, “What does this specific difference in the DNA sequence do to the biology of the cell?” We developed CRISPR over the past two and half years, but recently we came to realize that it would sometimes make imprecise, off-target modifications in the genome, and that’s a problem if our whole premise is that we are making precise changes to the genetic code without changing anything else in the cell. The paper in Cell describes a new approach that we found that makes editing much more precise; we show that we can overcome the off-target activity that we saw before.
Q4: What is the ultimate goal of your research?
FZ: It’s twofold: many of the diagnoses in medicine today are based on observation of symptoms. We don’t necessarily know what the cause of the disease or symptom is, so we just treat the symptom. One of my long-term goals is to make disease diagnosis more scientific by using genome editing to identify and understand the roles that genetic mutations play in disease. A second, more distant goal is to use genome editing to correct the genetic mutations that lead to disease. To do that in a therapeutic context we will have to be very precise; we don’t want to mutate other genes that are not involved in the disease. The work we did for the Cell paper takes us one step closer to reaching that therapeutic potential.
Q5: Your research has gotten a lot of attention over the last couple of years. What is it about your work that fascinates people?
FZ: I think people are excited for a few reasons. First, this technology allows many researchers to do what they’ve wanted to do for a long time: to manipulate the genome precisely. In the past, that could only be done in yeast, and to some extent in mice. Making genetic changes – however you want, in any organism you want – was not possible until about a year ago. I think that’s why people are excited – it opens up the door to studying more interesting biology in a wider variety of organisms. The second reason that I think people are excited is that this technology makes it really easy to work on things. Before, it would take a year or two to make a transgenic mouse; now they can do it in a few weeks. That ease of access is rapidly opening up new avenues for research.
Popular Science’s “Brilliant 10” list for 2013 appears in the magazine’s October issue.
Paper cited: Ran, FA et al., "Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity." Cell DOI: 10.1016/j.cell.2013.08.021.