Researcher: Feng Zhang

New gene-editing system precisely inserts large DNA sequences into cellular DNA

by Karen Zusi, Broad Institute |

A team led by researchers from Broad Institute of MIT and Harvard, and the McGovern Institute for Brain Research at MIT, has characterized and engineered a new gene-editing system that can precisely and efficiently insert large DNA sequences into a genome. The system, harnessed from cyanobacteria and called CRISPR-associated transposase (CAST), allows efficient introduction of DNA while reducing the potential error-prone steps in the process — adding key capabilities to gene-editing technology and addressing a long-sought goal for precision gene editing.

Precise insertion of DNA has the potential to treat a large swath of genetic diseases by integrating new DNA into the genome while disabling the disease-related sequence. To accomplish this in cells, researchers have typically used CRISPR enzymes to cut the genome at the site of the deleterious sequence, and then relied on the cell’s own repair machinery to stitch the old and new DNA elements together. However, this approach has many limitations.

Using Escherichia coli bacteria, the researchers have now demonstrated that CAST can be programmed to efficiently insert new DNA at a designated site, with minimal editing errors and without relying on the cell’s own repair machinery. The system holds potential for much more efficient gene insertion compared to previous technologies, according to the team.

The researchers are working to apply this editing platform in eukaryotic organisms, including plant and animal cells, for precision research and therapeutic applications.

The team molecularly characterized and harnessed CAST from two cyanobacteria, Scytonema hofmanni and Anabaena cylindrica, and additionally revealed a new way that some CRISPR systems perform in nature: not to protect bacteria from viruses, but to facilitate the spread of transposon DNA.

The work, appearing in Science, was led by first author Jonathan Strecker, a postdoctoral fellow at the Broad Institute; graduate student Alim Ladha at MIT; and senior author Feng Zhang, a core institute member at the Broad Institute, investigator at the McGovern Institute for Brain Research at MIT, the James and Patricia Poitras Professor of Neuroscience at MIT, and an associate professor at MIT, with joint appointments in the departments of Brain and Cognitive Sciences and Biological Engineering. Collaborators include Eugene Koonin at the National Institutes of Health.

A New Role for a CRISPR-Associated System

“One of the long-sought-after applications for molecular biology is the ability to introduce new DNA into the genome precisely, efficiently, and safely,” explains Zhang. “We have worked on many bacterial proteins in the past to harness them for editing in human cells, and we’re excited to further develop CAST and open up these new capabilities for manipulating the genome.”

To expand the gene-editing toolbox, the team turned to transposons. Transposons (sometimes called “jumping genes”) are DNA sequences with associated proteins — transposases — that allow the DNA to be cut-and-pasted into other places.

Most transposons appear to jump randomly throughout the cellular genome and out to viruses or plasmids that may also be inhabiting a cell. However, some transposon subtypes in cyanobacteria have been computationally associated with CRISPR systems, suggesting that these transposons may naturally be guided towards more-specific genetic targets. This theorized function would be a new role for CRISPR systems; most known CRISPR elements are instead part of a bacterial immune system, in which Cas enzymes and their guide RNA will target and destroy viruses or plasmids.

In this paper, the research team identified the mechanisms at work and determined that some CRISPR-associated transposases have hijacked an enzyme called Cas12k and its guide to insert DNA at specific targets, rather than just cutting the target for defensive purposes.

“We dove deeply into this system in cyanobacteria, began taking CAST apart to understand all of its components, and discovered this novel biological function,” says Strecker, a postdoctoral fellow in Zhang’s lab at the Broad Institute. “CRISPR-based tools are often DNA-cutting tools, and they’re very efficient at disrupting genes. In contrast, CAST is naturally set up to integrate genes. To our knowledge, it’s the first system of this kind that has been characterized and manipulated.”

Harnessing CAST for Genome Editing

Once all the elements and molecular requirements of the CAST system were laid bare, the team focused on programming CAST to insert DNA at desired sites in E. coli.

“We reconstituted the system in E. coli and co-opted this mechanism in a way that was useful,” says Strecker. “We reprogrammed the system to introduce new DNA, up to 10 kilobase pairs long, into specific locations in the genome.”

The team envisions basic research, agricultural, or therapeutic applications based on this platform, such as introducing new genes to replace DNA that has mutated in a harmful way — for example, in sickle cell disease. Systems developed with CAST could potentially be used to integrate a healthy version of a gene into a cell’s genome, disabling or overriding the DNA causing problems.

Alternatively, rather than inserting DNA with the purpose of fixing a deleterious version of a gene, CAST may be used to augment healthy cells with elements that are therapeutically beneficial, according to the team. For example, in immunotherapy, a researcher may want to introduce a “chimeric antigen receptor” (CAR) into a specific spot in the genome of a T cell — enabling the T cell to recognize and destroy cancer cells.

“For any situation where people want to insert DNA, CAST could be a much more attractive approach,” says Zhang. “This just underscores how diverse nature can be and how many unexpected features we have yet to find.”

Support for this study was provided in part by the Human Frontier Science Program, New York Stem Cell Foundation, Mathers Foundation, NIH (1R01-HG009761, 1R01-MH110049, and 1DP1-HL141201), Howard Hughes Medical Institute, Poitras Center for Psychiatric Disorders Research, J. and P. Poitras, and Hock E. Tan and K. Lisa Yang Center for Autism Research.

J.S. and F.Z. are co-inventors on US provisional patent application no. 62/780,658 filed by the Broad Institute, relating to CRISPR-associated transposases.

Expression plasmids are available from Addgene.

Scientists engineer new CRISPR platform for DNA targeting

by The Broad Institute |

A team that includes the scientist who first harnessed the revolutionary CRISPR-Cas9 and other systems for genome editing of eukaryotic organisms, including animals and plants, has engineered another CRISPR system, called Cas12b. The new system offers improved capabilities and options when compared to CRISPR-Cas9 systems.

In a study published today in Nature Communications, Feng Zhang and colleagues at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT, with co-author Eugene Koonin at the National Institutes of Health, demonstrate that the new enzyme can be engineered to target and precisely nick or edit the genomes of human cells. The high target specificity and small size of Cas12b from Bacillus hisashii (BhCas12b) as compared to Cas9 (SpCas9), makes this new system suitable for in vivo applications. The team is now making CRISPR-Cas12b widely available for research.

The team previously identified Cas12b (then known as C2c1) as one of three promising new CRISPR enzymes in 2015, but faced a hurdle: Because Cas12b comes from thermophilic bacteria — which live in hot environments such as geysers, hot springs, volcanoes, and deep sea hydrothermal vents — the enzyme naturally only works at temperatures higher than human body temperature.

“We searched for inspirations from nature,” Zhang said. “We wanted to create a version of Cas12b that could operate at lower temperatures, so we scanned thousands of bacterial genetic sequences, looking in bacteria that could thrive in the lower temperatures of mammalian environments.”

Through a combination of exploration of natural diversity and rational engineering of promising candidate enzymes, they generated a version of Cas12b capable of efficiently editing genomes in primary human T cells, an important initial step for therapeutics that target or leverage the immune system.

“This is further evidence that there are many useful CRISPR systems waiting to be discovered,” said Jonathan Strecker, a postdoctoral fellow in the Zhang Lab, a Human Frontiers Science program fellow, and the study’s first author.

The field is moving quickly: Since the Cas12b family of enzymes was first described in 2015 and demonstrated to be RNA-guided DNA endonucleases, several groups have have been exploring this family of enzymes. In 2017 a team from Jennifer Doudna’s lab at UC Berkeley reported that Cas12b from Alicyclobacillus acidoterrestris can mediate non-specific collateral cleavage of DNA in vitro. More recently, a team from the Chinese Academy of Sciences in Beijing reported that another Cas12b, from Alicyclobacillus acidiphilus, was used to edit mammalian cells.

The Broad Institute and MIT are sharing the Cas12b system widely. As with earlier genome editing tools, these groups will make the technology freely available for academic research via the Zhang lab’s page on the plasmid-sharing website Addgene, through which the Zhang lab has already shared reagents more than 52,000 times with researchers at nearly 2,400 labs in 62 countries to accelerate research.

Zhang is a core institute member of the Broad Institute of MIT and Harvard, as well as an investigator at the McGovern Institute for Brain Research at MIT, the James and Patricia Poitras Professor of Neuroscience at MIT, and an associate professor at MIT, with joint appointments in the departments of Brain and Cognitive Sciences and Biological Engineering.

Support for this study was provided by the Poitras Center for Psychiatric Disorders Research, the Hock E. Tan and K. Lisa Yang Center for Autism Research, the National Human Genome Research Institute, the National Institute of Mental Health, the National Heart, Lung, and Blood Institute, and other sources. Feng Zhang is an Investigator with the Howard Hughes Medical Institute.

References:

Strecker J, et al. Engineering of CRISPR-Cas12b for human genome editing. Nature Communications. Online January 22, 2019. DOI: 10.1038/s41467-018-08224-4.

Feng Zhang

Engineering Physiology

The primary focus of Feng Zhang’s work is to improve human health by discovering ways to modify cellular function and activity –  including the restoration of diseased, stressed, or aged cells to a more healthful state. His team is developing new molecular technologies to modify the cell’s genetic information, vehicles to deliver these tools into the correct cells, and larger-scale engineering to restore organ function. Zhang hopes to apply these approaches to neurodegenerative diseases, immune disorders, aging, and other disease states.

What is CRISPR?

by The Brain |

CRISPR (which stands for Clustered Regularly Interspaced Short Palindromic Repeats) is not actually a single entity, but shorthand for a set of bacterial systems that are found with a hallmarked arrangement in the bacterial genome.

When CRISPR is mentioned, most people are likely thinking of CRISPR-Cas9, now widely known for its capacity to be re-deployed to target sequences of interest in eukaryotic cells, including human cells. Cas9 can be programmed to target specific stretches of DNA, but other enzymes have since been discovered that are able to edit DNA, including Cpf1 and Cas12b. Other CRISPR enzymes, Cas13 family members, can be programmed to target RNA and even edit and change its sequence.

The common theme that makes CRISPR enzymes so powerful, is that scientists can supply them with a guide RNA for a chosen sequence. Since the guide RNA can pair very specifically with DNA, or for Cas13 family members, RNA, researchers can basically provide a given CRISPR enzyme with a way of homing in on any sequence of interest. Once a CRISPR protein finds its target, it can be used to edit that sequence, perhaps removing a disease-associated mutation.

In addition, CRISPR proteins have been engineered to modulate gene expression and even signal the presence of particular sequences, as in the case of the Cas13-based diagnostic, SHERLOCK.

Do you have a question for The Brain? Ask it here.

SHERLOCK: A CRISPR tool to detect disease

by Julie Pryor |

This animation depicts how Cas13 — a CRISPR-associated protein — may be adapted to detect human disease. This new diagnostic tool, called SHERLOCK, targets RNA (rather than DNA), and has the potential to transform research and global public health.

 

Feng Zhang wins 2018 Keio Medical Science Prize

Anne Trafton |

Molecular biologist Feng Zhang has been named a winner of the prestigious Keio Medical Science Prize. He is being recognized for the groundbreaking development of CRISPR-Cas9-mediated genome engineering in cells and its application for medical science.

Zhang is the James and Patricia Poitras Professor of Neuroscience at MIT, an associate professor in the departments of Brain and Cognitive Sciences and Biological Engineering, a Howard Hughes Medical Institute investigator, an investigator at the McGovern Institute for Brain Research, and a core member of the Broad Institute of MIT and Harvard.

“We are delighted that Feng is now a Keio Prize laureate,” says McGovern Institute Director Robert Desimone. “This truly recognizes the remarkable achievements that he has made at such a young age.”

Zhang is a molecular biologist who has contributed to the development of multiple molecular tools to accelerate the understanding of human disease and create new therapeutic modalities. During his graduate work, Zhang contributed to the development of optogenetics, a system for activating neurons using light, which has advanced our understanding of brain connectivity.

Zhang went on to pioneer the deployment of the microbial CRISPR-Cas9 system for genome engineering in eukaryotic cells. The ease and specificity of the system has led to its widespread use across the life sciences and it has groundbreaking implications for disease therapeutics, biotechnology, and agriculture. He has continued to mine bacterial CRISPR systems for additional enzymes with useful properties, leading to the discovery of Cas13, which targets RNA, rather than DNA, and may potentially be a way to treat genetic diseases without altering the genome. Zhang has also developed a molecular detection system called SHERLOCK based on the Cas13 family, which can sense trace amounts of genetic material, including viruses and alterations in genes that might be linked to cancer.

“I am tremendously honored to have our work recognized by the Keio Medical Prize,” says Zhang. “It is an inspiration to us to continue our work to improve human health.”

Now in its 23rd year, the Keio Medical Science Prize is awarded to a maximum of two scientists each year. The other 2018 laureate, Masashi Yanagisawa, director of the International Institute for Integrative Sleep Medicine at the University of Tsukuba, is being recognized for his seminal work on sleep control mechanisms.

The prize is offered by Keio University, and the selection committee specifically looks for laureates that have made an outstanding contribution to medicine or the life sciences. The prize was initially endowed by Mitsunada Sakaguchi in 1994, with the express condition that it be used to commend outstanding science, promote advances in medicine and the life sciences, expand researcher networks, and contribute to the wellbeing of humankind. The winners receive a certificate of merit, a medal, and a monetary award of approximately $90,000.

The prize ceremony will be held on Dec. 18 at Keio University in Tokyo.

Feng Zhang named winner of the 2018 Keio Medical Science Prize

Anne Trafton |

Feng Zhang and Masashi Yanagisawa have been named the 2018 winners of the prestigious Keio Medical Science Prize. Zhang is being recognized for the groundbreaking development of CRISPR-Cas9-mediated genome engineering in cells and its application for medical science. Zhang is an HHMI Investigator and the James and Patricia Poitras Professor of Neuroscience at MIT, an associate professor in MIT’s Departments of Brain and Cognitive Sciences and Biological Engineering, an investigator at the McGovern Institute for Brain Research, and a core member of the Broad Institute of MIT and Harvard. Masashi Yanagisawa, Director of the International Institute for Integrative Sleep Medicine at the University of Tsukuba, is being recognized for his seminal work on sleep control mechanisms.

“We are delighted that Feng is now a Keio Prize laureate,” says McGovern Institute Director Robert Desimone. “This truly recognizes the remarkable achievements that he has made at such a young age.”

The Keio Medical Prize is awarded to a maximum of two scientists each year, and is now in its 23rd year. The prize is offered by Keio University, and the selection committee specifically looks for laureates that have made an outstanding contribution to medicine or the life sciences. The prize was initially endowed by Dr. Mitsunada Sakaguchi in 1994, with the express condition that it be used to commend outstanding science, promote medical advances in medicine and the life sciences, expand researcher networks, and contribute to the well-being of humankind. The winners receive a certificate of merit, medal, and a monetary award of 10 million yen.

Feng Zhang is a molecular biologist who has contributed to the development of multiple molecular tools to accelerate our understanding of human disease and create new therapeutic modalities. During his graduate work Zhang contributed to the development of optogenetics, a system for activating neurons using light, which has advanced our understanding of brain connectivity. Zhang went on to pioneer the deployment of the microbial CRISPR-Cas9 system for genome engineering in eukaryotic cells. The ease and specificity of the system has led to its widespread use across the life sciences and it has groundbreaking implications for disease therapeutics, biotechnology, and agriculture. Zhang has continued to mine bacterial CRISPR systems for additional enzymes with useful properties, leading to the discovery of Cas13, which targets RNA, rather than DNA, and may potentially be a way to treat genetic diseases without altering the genome. He has also developed a molecular detection system called SHERLOCK based on the Cas13 family, which can sense trace amounts of genetic material, including viruses and alterations in genes that might be linked to cancer.

“I am tremendously honored to have our work recognized by the Keio Medical Prize,” says Zhang. “It is an inspiration to us to continue our work to improve human health.”

The prize ceremony will be held on December 18th 2018 at Keio University in Tokyo, Japan.

Advancing knowledge in medical and genetic sciences

Anne Trafton |

Research proposals from Laurie Boyer, associate professor of biology; Matt Shoulders, the Whitehead Career Development Associate Professor of Chemistry; and Feng Zhang, associate professor in the departments of Brain and Cognitive Sciences and Biological Engineering, Patricia and James Poitras ’63 Professor in Neuroscience, investigator at the McGovern Institute for Brain Research, and core member of the Broad Institute, have recently been selected for funding by the G. Harold and Leila Y. Mathers Foundation. These three grants from the Mathers Foundation will enable, over the next three years, key projects in the researchers’ respective labs.

Regenerative medicine holds great promise for treating heart failure, but that promise is unrealized, in part, due to a lack of sufficient understanding of heart development at the mechanistic level. Boyer’s research aims to achieve a deep, mechanistic understanding of the gene control switches that coordinate normal heart development. She then aims to leverage this knowledge and design effective strategies for rewiring faulty circuits in aging and disease.

“We are very grateful to receive support and recognition of our work from the Mathers Foundation,” said Boyer. “This award will allow us to build upon our prior work and to embark upon high risk projects that could ultimately change how we think about treating diseases resulting from faulty wiring of gene expression programs.”

Shoulders’ goal, with this support from the Mathers Foundation, is to elucidate underlying causes of osteoarthritis. There is currently no cure for osteoarthritis, which is perhaps the most common aging-related disease and is characterized by a progressive deterioration of joint cartilage culminating in inflammation, debilitating pain, and joint dysfunction. The Shoulders Group aims to test a new model for osteoarthritis — specifically, the concept that a collapse of proteostasis in aging cartilage cells creates an unrecoverable cartilage repair defect, thus initiating a self-amplifying, destructive feedback loop leading to pathology. Proteostasis collapse in aging cells is a well-known, disease-causing phenomenon that has previously been considered primarily in the context of neurodegenerative disorders. If correct, the proteostasis collapse model for osteoarthritis could one day lead to a novel class of therapeutic options for the disease.

“We are delighted to receive this generous support from the Mathers Foundation, which makes it possible for us to pursue an outside-the-box, high-risk/high-impact idea regarding the origins of osteoarthritis,” said Shoulders. “The research we are now able to pursue will not only provide fundamental, molecular-level insights into joint function, but also could change how we think about this widespread disease.”

Many genetic diseases are caused by the change of just a single base of DNA. Zhang is a leader in the field of genome editing, and he and his team have developed an array of tools based on the microbial immune CRISPR-Cas systems that can manipulate DNA and RNA in human cells. Together, these tools are changing the way molecular biology research is conducted, and they hold immense potential as therapeutic agents to correct thousands of genetic diseases. Now, with the support of the Mathers Foundation, Zhang is working to realize this potential by developing a CRISPR-based therapeutic that works at the level of RNA and offers a safe, effective route to treating a range of diseases, including diseases of the brain and central nervous system, which are difficult to treat with existing gene therapies.

“The generous support from the Mathers Foundation allows us the freedom to explore this exciting new direction for CRISPR-based technologies,” Zhang stated.

Known for their generosity and philanthropy, G. Harold and Leila Y. Mathers created their foundation with the goal of distributing their wealth among sustainable, charitable causes, with a particular interest in basic scientific research. The Mathers Foundation, whose ongoing mission is to advance knowledge in the life sciences by sponsoring scientific research and applying learnings and discoveries to benefit mankind, has issued grants since 1982.

Ed Boyden and Feng Zhang named Howard Hughes Medical Institute Investigators

Anne Trafton |

Two members of the MIT faculty were named Howard Hughes Medical Institute (HHMI) investigators today. Ed Boyden and Feng Zhang join a community of 300 HHMI scientists who are “transforming biology and medicine, one discovery at a time.” Both researchers have been instrumental in recognizing, developing, and sharing robust tools with broad utility that have revolutionized the life sciences.

“We are thrilled that Ed and Feng are being recognized in this way” says Robert Desimone, director of the McGovern Institute for Brain Research at MIT. “Being named to the investigator program recognizes their previous achievements and allows them to follow the innovative path that is a trait of their research.”

HHMI selects new Investigators to join its flagship program through periodic competitions. In choosing researchers to join its investigator program, HHMI specifically aims to select ‘people, not projects’ and identifies trail blazers in the biomedical sciences. The organization provides support for an unusual length of time, seven years with a renewal process at the end of that period, thus giving selected scientists the time and freedom to tackle difficult and important biological questions. HHMI-affiliated scientists continue to work at their home institution. The HHMI Investigator program currently funds 300 scientists at 60 research institutions across the United States.

Ed Boyden, the Y. Eva Tan Professor in Neurotechnology at MIT, has pioneered a number of technologies that allow visualization and manipulation of complex biological systems. Boyden worked, along with Karl Deisseroth and Feng Zhang, on optogenetics, a system that leverages microbial opsins to manipulate neuronal activity using light. This technology has transformed our ability to examine neuronal function in vivo. Boyden’s work initiated optogenetics, then extended it into a multicolor, high-speed, and noninvasive toolbox. Subsequent technological advances developed by Boyden and his team include expansion microscopy, an imaging strategy that overcomes the limits of light microscopy by expanding biological specimens in a controlled fashion. Boyden’s team also recently developed a directed evolution system that is capable of robotically screening hundreds of thousands of mutated proteins for specific properties within hours. He and his team recently used the system to develop a high-performance fluorescent voltage indicator.

“I am honored and excited to become an HHMI investigator,” says Boyden, who is also a member of MIT’s McGovern Institute for Brain Research and Koch Institute for Integrative Cancer Research and an associate professor in the Program in Media Arts and Sciences at the MIT Media Lab; the MIT Department of Brain and Cognitive Sciences; and the MIT Department of Biological Engineering. “This will give my group the ability to open up completely new areas of science, in a way that would not be possible with traditional funding.”

Feng Zhang is a molecular biologist focused on building new tools for probing the human brain. As a graduate student, Zhang was part of the team that developed optogenetics. Zhang went on to develop other innovative tools. These achievements include the landmark deployment of the microbial CRISPR-Cas9 system for genome engineering in eukaryotic cells. The ease and specificity of the system has led to its widespread use. Zhang has continued to mine bacterial CRISPR systems for additional enzymes with useful properties, leading to the discovery of Cas13, which targets RNA, rather than DNA. By leveraging the unique properties of Cas13, Zhang and his team created a precise RNA editing tool, which may potentially be a safer way to treat genetic diseases because the genome does not need to be cut, as well as a molecular detection system, termed SHERLOCK, which can sense trace amounts of genetic material, such as viruses.

“It is so exciting to join this exceptional scientific community,” says Zhang, “and be given this opportunity to pursue our research into engineering natural systems.”

Zhang is the James and Patricia Poitras Professor of Neuroscience at MIT, an associate professor in the MIT departments of Brain and Cognitive Sciences and Biological Engineering, an investigator at the McGovern Institute for Brain Research, and a core member of the Broad Institute of MIT and Harvard.

The MIT Media Lab, Broad Institute of MIT and Harvard, and MIT departments of Brain and Cognitive Sciences and Biological Engineering contributed to this article.

Feng Zhang elected to National Academy of Sciences

Anne Trafton |

Feng Zhang has been elected to join the National Academy of Sciences (NAS), a prestigious, non-profit society of distinguished scholars that was established through an Act of Congress signed by Abraham Lincoln in 1863. Zhang is the Patricia and James Poitras ’63 Professor in Neuroscience at MIT, an associate professor in the departments of Brain and Cognitive Sciences and Biological Engineering, an investigator at the McGovern Institute for Brain Research, and a core member of the Broad Institute of MIT and Harvard. Scientists are elected to the National Academy of Sciences by members of the organization as recognition of their outstanding contributions to research.

“Because it comes from the scientific community, election to the National Academy of Sciences is a very special honor,” says Zhang, “and I’m grateful to all of my colleagues for the recognition and support.”

Zhang has revolutionized research across the life sciences by developing and sharing a number of powerful molecular biology tools, most notably, genome engineering tools based on the microbial CRISPR-Cas9 system. The simplicity and precision of Cas9 has led to its widespread adoption by researchers around the world. Indeed, the Zhang lab has shared more than 49,000 plasmids and reagents with more than 2,300 institutions across 62 countries through the non-profit plasmid repository Addgene.

Zhang continues to pioneer CRISPR-based technologies. For example, Zhang and his colleagues discovered new CRISPR systems that use a single enzyme to target RNA, rather than DNA. They have engineered these systems to achieve precise editing of single bases of RNA, enabling a wide range of applications in research, therapeutics, and biotechnology. Recently, he and his team also reported a highly sensitive nucleic acid detection system based on the CRISPR enzyme Cas13 that can be used in the field for monitoring pathogens and other molecular diagnostic applications.

Zhang has long shown a keen eye for recognizing the potential of transformative technologies and developing robust tools with broad utility. As a graduate student in Karl Diesseroth’s group at Stanford, he contributed to the development of optogenetics, a light-based technology that allows scientists to both track neurons and causally test outcomes of neuronal activity. Zhang also created an efficient system for reprogramming TAL effector proteins (TALEs) to specifically recognize and modulate target genes.

“Feng Zhang is unusually young to be elected into the National Academy of Science, which attests to the tremendous impact he is having on the field even at an early stage of his career, “ says Robert Desimone, director of the McGovern Institute for Brain Research at MIT.

This year the NAS, an organization that includes over 500 Nobel Laureates, elected 84 new members from across disciplines. The mission of the organization is to provide sound, objective advice on science to the nation, and to further the cause of science and technology in America. Four MIT professors were elected this year, with Amy Finkelstein (recognized for contributions to economics) as well as Mehran Karder and Xiao-Gang Wen (for their research in the realm of physics) also becoming members of the Academy.

The formal induction ceremony for new NAS members will be held at the Academy’s annual meeting in Washington D.C. next spring.