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The field of synthetic biology seeks to extract living organisms’ extensive capabilities and implement them in new contexts for useful functions, enabling impactful applications in medicine, manufacturing, agriculture, and sustainability. The grand vision of synthetic biology is to enable biology by design – applying engineering principles (modularity, standardization, and automation) to develop a systematic framework to design biological systems from the ground instead of modifying existing organisms using one-off, non-generalizable approaches.

Although synthetic biology has progressed significantly in the past decades, most efforts have focused on designing biology (applying engineering to existing biology), not biology by design (building biology from the ground up with a defined purpose). This skewed focus presents significant challenges in the practical application of engineered biological systems, where the cells’ need to adapt and survive clashes with engineers’ need to execute designed functions.

We can only realize synthetic biology's true potential when we achieve biology by design. This vision is the foundation of my research program, where my lab will establish a framework toward biology by design using cell-free synthetic biology and showcase its transformative potential in developing precision medicine against antibiotic resistance.

Why cell-free systems? Cell-free systems harness living cells’ gene expression capability to perform the same function without having to keep the cells alive. A typical cell-free reaction consists of just three components: the machinery for gene expression, the energy to power gene expression, and the DNA program coding for gene expression. By removing the burden of cell survival and the membrane barrier, cell-free systems allow precise engineering and execution of desired functions beyond the constraints of living cells, making them the ideal platform to enable biology by design.

Why precision medicine against antibiotic resistance? We have relied on antibiotics to treat bacterial infections for decades. However, years of antibiotic misuse and overuse have given rise to antibiotic-resistant bacteria. With a dwindling pipeline for new antibiotics, once-treatable infections can be deadly as we enter the post-antibiotic era. There is a dire need to develop a precise treatment for antibiotic-resistant infections without aggravating the current problem.

Research Focus: Cell-free synthetic biology by design to develop precision phage therapy.

Bacteriophages (phages) are bacterial viruses that infect their hosts with remarkable precision. They use specific receptor-binding proteins to recognize biomarkers on bacteria’s outer membrane. Upon recognition, phages inject their genetic material into the host cell, hijack the cellular machinery to replicate, and eventually lyse the host to release new phages for infection. As a result, phage therapy can be an effective approach to counter antibiotic resistance while minimizing their environmental footprint.

However, notable challenges in phage production, engineering, and characterization have presented significant roadblocks to phage therapy’s clinical adoption. Using an integrated approach of cell-free proteome engineering, genome modularization, and bottom-up synthetic phage design, my lab will use cell-free synthetic biology by design to develop precision phage therapy.

Teaching Interests:

Learning, to me, is a life-long endeavor. Thus, my teaching goal is to help students develop a systematic approach to learning focused on aligning personal motivations and applying effective learning techniques. Students leaving my classroom will not only master the learning outcomes but also possess the skills to continually apply and adapt their learning in various contexts of their careers. My teaching approach is based on my past teaching and mentoring experiences and personal academic journey. As a teacher and a mentor, I aspire to meet my students where they are and guide them to develop effective, personalized learning approaches through the following methodologies:

1. Promote learner motivation by communicating and aligning learning goals.
2. Enhancing learning and developing critical thinking skills using active learning approaches.
3. Creating an inclusive learning environment by adopting a growth mindset.

Lastly, my chemical and biomolecular engineering training has prepared me to teach undergraduate core courses in numerical methods, chemical reactions and kinetics, and transport phenomena. I am also interested in teaching undergraduate and graduate classes rooted in synthetic biology, biomolecular engineering, and bioprocesses.

Commitment to DEI:

As a former McNair Scholar and a first-generation college student, I am especially committed to raising awareness, accessibility, and opportunities in STEM research to underrepresented groups. As a postdoctoral fellow at Caltech, I have joined the Caltech Connection outreach program to mentor students in neighboring community colleges. At Georgia Tech, I have actively recruited students from underrepresented groups into undergraduate research and mentored 4 undergraduate researchers. Outside of universities, I am part of the Engineering Biology Research Consortium’s effort to extend the reach of synthetic biology beyond research-intensive (R1) institutions. I am also a long-time mentor for the international Genetically Engineering Machines (iGEM) – where I have mentored 2 collegiate teams and 1 women-majority high school team to compete in the annual iGEM Jamboree. My mentorship effort has been recognized with the Most Dedicated Mentor Award by the iGEM community in 2021.

The advancement of science depends on diverse experiences and perspectives, and I am driven to promote diversity and inclusion through my research, mentorship, teaching, and outreach activities.

For a complete list of my research, teaching, mentoring, and outreach activities, visit https://yzhang952.github.io.