Dr. Stanley Qi is Assistant Professor in the Department of Bioengineering, Department of Chemical and Systems Biology, and ChEM-H Institute at Stanford University. He received a BS in physics from Tsinghua University and a Ph.D. in bioengineering from the University of California, Berkeley. During his doctorate he studied synthetic biology with Dr. Adam Arkin and researched CRISPR biology with Dr. Jennifer Doudna.

After completing his doctorate, he skipped the postdoc training and conducted independent research as a systems biology faculty fellow at the UCSF. He joined Stanford in 2014. As a synthetic biologist, he developed the nuclease-dead dCas9 system, which significantly expands the CRISPR toolbox. Together with other researchers, he invented the technologies CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) for precise gene regulation. The work in his laboratory resulted in novel CRISPR tools for epigenome editing, 3D genome structure control and DNA / RNA imaging. Using approaches from synthetic biology, his laboratory developed CRISPR-based antiviral agents for the treatment of SARS-CoV-2 and other RNA viruses. He won the Early Independence Award from the NIH Director, Pew Biomedical Scholar, Alfred. P. Sloan Fellowship and an NSF CAREER Award.

I met with Dr. Qi met to find out more about his career so far and what the ACS Synthetic Biology For him, award means.

What does this award mean to you?

I am very happy about this award. When I was a PhD student thirteen years ago, I decided to switch my major from physics to bioengineering after realizing the craze for synthetic biology. It wasn’t an easy process, but I enjoyed synthetic biology research. Although there are many challenges that we do not have to solve for a long time, I am pleased that our efforts are recognized by this award.

What are you working on now

My laboratory develops CRISPR technologies as novel therapeutics for the treatment of infectious diseases and regenerative medicine. Finding safe and effective solutions to treat incurable diseases in medicine has been a dream for us, and synthetic biology has become a major pioneer. For example, we developed CRISPR using biomolecular engineering and gene design principles in synthetic biology as a novel tool for the precise regulation of many genes in human cells. We used these tools to turn genes on and off, which gives us new ways to make cells’ “inner DNA circuitry” flexible, such as precisely converting human stem cells into neurons or creating a better tumor finder. and killing behavior of immune cells.

How would you describe your research to someone outside your research area?

CRISPR technology is known as a technological breakthrough in gene editing. We apply synthetic biology approaches to push CRISPR technology beyond editing. For example, we’re helping develop a technology called CRISPR interference and CRISPR activation, known as CRISPRi and CRISPRa. CRISPRi / a interacts with DNA to silence or activate certain genes without altering the DNA sequence, creating the ability to convert stem cells into therapeutic cells such as neurons. We are modifying CRISPR as an imaging tool to record real-time “movies” of the dynamic process of gene transcription and the movement of chromosomes. We also developed a CRISPR tool to construct the three-dimensional “DNA origami” structure of the genome to study human diseases in relation to the genome structure. We recently turned traditional CRISPR into antiviral therapy to find and destroy RNA viruses that show promise for treating COVID-19 and the flu.

In your opinion, what is currently the greatest challenge in your research area?

Biological research has generally remained a trial and error process. While synthetic biology seeks to make biological research more predictable, customizable, and ultimately more programmable, it still faces many challenges. Take molecular engineering as an example. While synthetic biologists often need to develop molecules (e.g. naturally derived or newly developed proteins) with new desired functions, this process has been tedious and sometimes unpleasant. We need new design principles, experimental approaches and computer tools to improve biological design. Fortunately, with the availability of powerful, high-throughput synthetic biology approaches to generate huge amounts of data, either work or non-work, as well as computational methods of analyzing the data (e.g., machine learning), we see a future that can make “engineering biology” easier and simpler make it more predictable.

Have there been highlights in your career so far that you are particularly proud of?

I was fortunate enough to witness the emergence and development of the CRISPR field and was glad that I was able to make some contributions to this field. One research topic I’m proud of is the development of the nuclease-dead Cas9 (which I called dCas9) in 2012, which was published in early 2013 when the CRISPR field was still in its infancy. The dCas9 system later became the basis and platform for many RNA-controlled applications and supported the development of CRISPRi / a, epigenome editing, chromatin imaging, base editing and prime editing. It also facilitated the use of CRISPR as “wires” to construct elaborate circuits that were used to control metabolic flow, record cellular stimuli, and perform genetic screens. The development of the nuclease-dead dCas9 has greatly expanded CRISPR’s toolbox for genome engineering applications beyond nuclease-mediated gene editing.

Did you receive advice that was particularly helpful?

As a PhD student, I was curious about how a fresh student like me could become an independent researcher. With this question I gave my Ph.D. Consultant, Dr. Adam Arkin. I still remember exactly, he replied, “You should have a 30 year old dream”. I didn’t see at that moment how this could help me become a better researcher. Later in my career, either by enjoying the exciting moments of discovery or backing up the struggles with experimental failures, I begin to realize the importance of having a very long vision. Probably with only this type of vision, we are less likely to be blinded by short-term successes or failures, and also not get bored getting to the next stop.

What advice would you give to someone just starting out in the industry?

Keep your dream, but start with something simple. Keep exploring. There are so many exciting topics in synthetic biology and I’m pretty sure the best in synthetic biology is yet to come.

View articles written by Dr. Qi have been published in the journals of ACS Publications.

Dr. Qi will be speaking at the Synthetic Biology: Engineering, Evolution & Design (SEED) Meeting 2021 on Friday June 18th. Join Dr. Virtual Qi at 11:25 am PDT for his lecture “ACS Synthetic Biology Young Innovator Award: Synthetic biology for mammalian cell engineering and antiviral agents”. The full technical program can be found here.


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