Major areas of focus include:
I. Controlling the brain's genetic programs
Feng Zhang and his colleagues are designing new molecular tools for manipulating the living brain. As a student, Zhang 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. His lab 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.
II. Designer proteins
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.
The Zhang lab 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.
III. Modeling brain disorders
By applying these and other methods, Zhang and his colleagues hope to generate new animal models of human disease in order to study their underlying biological mechanisms. The lab 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.