Meet Feng Zhang: Revolutionizing gene editing and brain research
Feng Zhang, Biography / Current Status
McGovern Institute Profile
Biography / Current Status. Feng Zhang joined the McGovern Institute in 2011. He is also a core member of the Broad Institute, the W. M. Keck Career Development Professor in Biomedical Engineering, and an assistant professor in the MIT department of Brain and Cognitive Sciences. He obtained a bachelor’s degree from Harvard University and a PhD in chemistry and bioengineering from Stanford University. Before joining the MIT faculty he was a junior fellow of the Harvard University Society of Fellows. He is a Searle Scholar, and has received both a Director’s Transformative Research Award and a Directors’ Pioneer Award from the National Institutes of Health. In 2012 he shared the UNC/Perl Prize for his role in the development of optogenetics.
Feng Zhang, Early Life and Education
Early Life and Education. Zhang was born in China and during his childhood moved to Iowa, where he attended Theodore Roosevelt High School in Des Moines, graduating in 2000. In 1999 he attended the Research Science Institute at MIT, and in 2000 he won 3rd Place in the Intel Science Talent Search. He earned his A.B. in Chemistry and Physics from Harvard University in 2004 and his Ph.D. in chemistry and bioengineering from Stanford University in 2009 under the guidance of Karl Deisseroth where he developed the technologies behind optogenetics with Edward Boyden. He served as an independent Junior Fellow in the Harvard Society of Fellows and collaborated with George M. Church and Paola Arlotta on using synthetic biology to study the patterns of gene activity during brain development, a topic with implications for neurological and psychiatric problems. While a Junior Fellow, Zhang engineered the TAL effector (TALE) system — programmable DNA binding proteins that can be easily customized to target novel DNA sequences — for targeting and activating genes of mammalian genomes.
Feng Zhang, Early Research
Research. Zhang's lab is focused on using synthetic biology to develop technologies for genome and epigenome engineering to study neurobiology. As a postdoc, he began work on using TAL effectors to control gene transcription. However, given the difficulty of using such tools, he looked to develop new genome-editing tools better suited for his research. In 2011, Zhang studied the scientific literature on the CRISPR system and, synthesizing evidence from existing foundational studies of the natural system, including a study by Sylvain Moineau’s group describing the DNA-cleavage activity of Cas9, he set out to harness the CRISPR system (found only in prokaryotic cells) for genome editing in mammalian/human cells.
Through a series of experiments, Zhang’s group successfully demonstrated the application of Cas9 proteins harnessed from both Streptococcus pyogenes and Streptococcus thermophilus along with appropriate CRISPR RNA guides for genome editing in human cells, publishing their work in the journal Science on January 3, 2013. His laboratory continues to refine and improve upon the CRISPR/Cas9 system and to develop novel genome-engineering technologies aimed at perturbing and editing the genome for disease research.
Zhang’s team has shared CRISPR reagents and tips with thousands of laboratories, and continues to make all of its CRISPR tools available to the academic research community directly and via the plasmid-sharing website, Addgene. Addgene has distributed CRISPR plasmids deposited by Zhang more than 14,000 times since his team’s first publication in January 2013.
Feng Zhang, Current Research
McGovern Institute Profile
Controlling the brain's genetic programs
Feng Zhang is designing new molecular tools for manipulating the living brain. As a student, he played a major role in the development of optogenetics, a technology by which the brain’s electrical activity can be controlled with light-sensitive proteins. He is now working to extend this molecular engineering approach to other aspects of brain function such as gene expression, and to develop new approaches to understanding and eventually treating brain diseases.
Genome editing with CRISPR-Cas9
Feng Zhang is a leader in the development of the CRISPR-Cas9 system, a genome editing technology that allows scientists to make precise changes to a DNA sequence. This scientific advance is expected to transform many areas of biomedical research and may ultimately form the basis of new treatments for human genetic disease.
The mammalian brain expresses around 20,000 genes, and a method to regulate their activity with precise specificity would be of great value as a research tool. It could also lead to new therapies for brain disorders, many of which involve abnormal patterns of gene expression. As a junior fellow at Harvard, Zhang developed a new method for constructing customized DNA-binding proteins. These proteins, known as TAL-effectors, can be produced quickly and cheaply using the new method, and can be targeted to any desired DNA sequence.
Zhang plans to use TAL effectors to manipulate brain gene expression, using several different approaches. These proteins can be used to introduce changes into the genome of a cell, for example introducing defined mutations for experimental work or repairing genetic mutations as a potential therapy for certain genetic diseases. TAL effectors can also be designed to influence gene expression in other ways, for example activating or blocking the transcription of the targeted genes.
Modeling brain disorders
By applying these and other methods, Zhang hopes to generate new animal models of human disease in order to study their underlying biological mechanisms. He is especially interested in complex disorders, such as psychiatric and neurological diseases, that are caused by multiple genetic and environmental risk factors and which are difficult to model using conventional methods. Zhang’s method may also lead to new ways to produce brain stem cells, which could be used as a platform for developing new drugs and as a new source of material for transplantation in many human degenerative diseases.
References / Additional Info
Wikipedia, Feng Zhang
Feng Zhang: The Midas of Methods (The Scientist Magazine)
Using Genomic Research to Pierce Mental Illness (MIT Technological Review)
Broad Institute Article, Feng Zhang
Tools: Links to Software by the Broad Institute