ACS Synthetic Biology Young Innovator Award Goes to Dr. Lei Stanley Qi - ACS Axial | ACS Publications

ACS Synthetic Biology Young Innovator Award Goes to Dr. Lei Stanley Qi

Dr. Stanley Qi is an assistant professor in the Department of Bioengineering, Department of Chemical and Systems Biology, and ChEM-H Institute at Stanford University. He obtained B.S. in Physics from Tsinghua University and Ph.D. in Bioengineering from the University of California, Berkeley. During his Ph.D., he studied synthetic biology with Dr. Adam Arkin and explored CRISPR biology with Dr. Jennifer Doudna.

After his Ph.D., he skipped postdoc training and performed independent research as a Systems Biology Faculty Fellow at UCSF. He joined Stanford in 2014. As a synthetic biologist, he developed the nuclease-dead dCas9 system, which greatly expands the CRISPR toolbox. Along with other researchers, he invented the CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) technologies for precise gene regulation. The work in his lab led to novel CRISPR tools for epigenome editing, 3D genome structure control, and DNA/RNA imaging. Using synthetic biology approaches, his lab developed CRISPR-based antivirals to treat SARS-CoV-2 and other RNA viruses. He won NIH Director’s Early Independence Award, Pew Biomedical Scholar, Alfred. P. Sloan Fellowship and an NSF CAREER Award.

I caught up with Dr. Qi to find out more about his career to date and what the ACS Synthetic Biology award means to him.

What does this award mean to you?

I am very excited to receive this award. When I was a graduate student thirteen years ago, I decided to change my major from physics to bioengineering after learning about the excitement in synthetic biology. It wasn’t an easy process, but I have enjoyed synthetic biology research. Although we still have a long way to solve many challenges, I am glad to see our efforts have received recognition from this award.

What are you working on now?

My lab has been developing CRISPR technologies as novel therapeutics to treat infectious diseases and regenerative medicine. It has been a dream for us to find safe and effective solutions to treat incurable diseases in medicine, and synthetic biology has become a key enabler. For example, using biomolecular engineering and gene design principles in synthetic biology, we developed CRISPR as a novel tool to precisely regulate many genes in human cells. We used these tools to switch on and off genes, which gives us new power to flexibly engineer the ‘inner DNA circuitry’ of cells, such as precisely converting human stem cells into neurons or creating better tumor-seeking and killing behaviors of immune cells.

How would you describe your research to someone outside your field of research?

CRISPR technology has become well known as a technological breakthrough to edit genes. We apply synthetic biology approaches to push the CRISPR technology to new limits beyond editing. For example, we help create a technology called CRISPR interference and CRISPR activation, known as CRISPRi and CRISPRa. CRISPRi/a interacts with DNA to silence or activate specific genes without altering the DNA sequence, which creates the ability to change stem cells into therapeutic cells such as neurons. We modify CRISPR as an imaging tool to capture real-time “movies” of the dynamic process of gene transcription and the movement of chromosomes. We also developed a CRISPR tool to engineer the 3-dimensional ‘DNA origami’ structure of the genome, to study human diseases related to the genome structure. Recently, we transformed the traditional CRISPR into an antiviral therapy to seek and destroy RNA viruses, which shows promise to treat COVID-19 and the flu.

What do you think is the biggest challenge currently in your area of research?

Biological research, in general, has remained a trial-and-error process. Synthetic biology, while trying to make biological research more predictable, designable, and ultimately programmable, still faces a lot of challenges. Take molecular engineering as an example. While synthetic biologists frequently need to engineer molecules (e.g., proteins derived from Nature or de novo designed) with new desired functions, this process has been tedious and sometimes unpleasant. We need new design principles, experimental approaches, and computational tools to make the biological design better. Fortunately, with the availability of powerful high-throughput synthetic biology approaches to generate huge amounts of data, either working or non-working data, as well as computational methods to analyze the data (e.g., machine learning), we see a future that can make ‘engineering biology’ easier and more predictable.

Have there been any highlights in your career to date that you are especially proud of?

I was lucky to witness the birth and development of the CRISPR field and was glad that I was able to make some contributions to the field. One research topic that I am proud of is the development of the nuclease dead Cas9 (which I named dCas9) in 2012, which was published in early 2013 when the CRISPR field was still in its infancy. The dCas9 system later became a basis and a platform for many RNA-guided applications and aided 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 sophisticated circuits that were used to control metabolic flux, record cellular stimuli, and perform genetic screens. The development of the nuclease-dead dCas9 greatly expanded the toolbox of CRISPR for applications of genome engineering beyond nuclease-mediated gene editing.

Have you received any advice that you’ve found particularly helpful?

When I was a graduate student, I was curious how a fresh student like me can become an independent researcher. With this question, I asked my Ph.D. advisor, Dr. Adam Arkin. I clearly remember, he answered, “you should have a 30-year dream”. It wasn’t clear to me how this could help me become a better researcher at that moment. Later as I progress in my career, either by enjoying the exciting moments of discovery or ensuring the struggles from experimental failures, I start to realize how important it is to have a very long vision. Probably only with this type of vision, we will be less likely to be blinded by near-term successes or failures, nor get bored to progress to the next stop.

What would your advice be to someone just starting out in the field?

Keep your dream, but start with something simple. Keep exploring. There are so many exciting topics in synthetic biology, and I am almost certainly sure that the best of synthetic biology is yet to come.

View articles published by Dr. Qi in ACS Publications journals.

Dr. Qi will be presenting during the 2021 Synthetic Biology: Engineering, Evolution & Design (SEED) Meeting on Friday, June 18th. Join Dr. Qi virtually at 11:25 A.M. PDT for his talk ‘ACS Synthetic Biology Young Innovator Award: Synthetic biology for mammalian cell engineering and antivirals.’ See the full technical program here.

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