(4ju) Discovering Functional Monomer Sequence in Synthetic Polymers

Research Interests:

Imagine a world in which all polymers – not just proteins and nucleic acids – had defined, evolvable sequences to solve challenges in energy, catalysis, and nano-bio interfaces. Towards this vision, my research seeks to identify functional sequences in synthetic polymers by developing approaches for synthesizing, screening, and sequencing sequence-controlled polymers (SCPs). The concept of SCPs, rooted in the critical role of monomer sequences in biology, has intrigued researchers since the advent of modern polymer science. For biopolymers such as DNA and proteins, we have readily accessible tools to evolve their sequences for new functions. However, we currently lack the ability to navigate the massive, high-dimensional sequence space in synthetic polymers. These functional sequences in synthetic polymers are not only undiscovered, but currently undiscoverable.

To overcome the current bottleneck in discovering functional SCPs, my research program will integrate latest advances in controlled polymerization methods with in silico polymer sequence design, reaction kinetic engineering, multiscale experimental characterizations, and DNA nanotechnologies. By utilizing thermodynamic and kinetic controls synergistically during synthesis, we will regulate the comonomer sequence along polymer chain to develop metallopolymers for catalysis and electron transfer (research area 1). These advances will enable us to produce SCPs in a scalable manner, which has been called the “Holy Grail” of polymer synthesis. By examining polymer topological isomers, which have identical chemical formulas but different internal connectivity and structural dynamics, we seek to understand how structural dynamics affect the properties of protein-mimicking polymers (research area 2). This finding will offer new design framework beyond the traditional static design parameters such as size, shape, and side-chain chemistry. By leveraging DNA sequencing technology, we will pioneer a high-throughput method for screening and sequencing synthetic polymers that provide optimal ligand presentations at nano-bio interfaces (research area 3). Employing this approach will enable rapid exploration of sequences across vast polymer pools within a single test tube, circumventing the conventional hurdle of examining SCPs individually.

The advances in these three thrusts will enable us to control and decipher the sequence of synthetic polymers for discovering functional sequences, as performed in proteomics and genomics. These research efforts will surpass the compositional control of soft materials previously achieved, leading to new applications in enzyme-like catalysis, biological surface interfacing, and information storage, etc. In addition, the defined monomer arrangement in SCPs will offer a foundational framework for understanding how local molecular structure, chemical identity, and molecular ordering control the form and function in soft matters.

Research Experience:

Postdoctoral: Rational Design of Random Heteropolymers for Catalytic Activity

California Institute for Quantitative Biosciences, University of California, Berkeley (advised by Prof. Ting Xu)

My postdoctoral research has focused on designing synthetic heteropolymers to replicate the functions of structured proteins such as enzymes. Inspired by the intimate sequence-property correlation in proteins, researchers have long sought to modulate the monomer sequence of synthetic polymers to attain functional complexity reminiscent of those seen in proteins. However, even with a limited set of monomers, the sequence space for synthetic polymers is massive. Therefore, new paradigms are required to navigate in this vast, high-dimensional sequence space and accelerate material discovery. Leveraging in silico sequence analysis, we have engineered the segmental chemical characteristics of random heteropolymers (RHPs) to achieve protein-like properties. Orthogonal to the approaches pursuing monomeric sequence specificity, RHP samples a reduced sequence space within a given monomer composition. Through this strategy, RHPs have demonstrated catalytic capabilities in various reactions, robustness at interfaces, and efficient degradation of environmentally persistent chemicals. In addition to exploring new avenues for replicating protein functions using synthetic polymers, this work provides a framework for designing functional polymers by considering the sequence distribution at segmental level.

Graduate: Investigation of Sequence-Property Relations in Precisely Defined Synthetic Macromolecules

Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign (advised by Profs. Jeffrey S. Moore and Charles M. Schroeder)

My dissertation research aimed to gain a fundamental understanding on how monomer sequence affects the charge transport properties in conjugated polymers. A grand challenge in synthetic polymers is deciphering the influence of primary monomer sequence on material properties. The challenge is twofold. The first difficulty lies in efficient production of synthetic polymer with defined monomer sequence and chain length. Beyond the synthetic challenge, developing new molecular characterization method is critically needed for directly probing the intrinsic sequence-property correlations at molecular level. To address this challenge, I established a new iterative synthesis approach to prepare conjugated oligomers with precisely defined structures, and their charge transport properties were directly characterized through single-molecule conductance measurements. My works have demonstrated that conjugated oligomers with identical compositions but different monomer sequences exhibit dramatically different charge transport pathways, some of which enhance conductance more than 10-fold. A systematic analysis using structural analogues further revealed the role of directionality and steric hinderance of heterocycles in determining the charge transport behaviors. Overall, these findings present a molecular-level understanding on the sequence-conductance correlations in conjugated polymers. Considering the promise of molecular electronics in advancing semiconductor manufacturing beyond Moore’s Law, we envision that synthetic polymer with defined monomer sequence presents new avenues for designing functional components in molecular circuits.

Teaching Interests:

As a chemical engineer by training, I am excited and qualified to teach core chemical engineering courses such as thermodynamics, transport phenomena, reaction kinetics, and reactor design, as well as more specialized courses in polymer science and engineering. I also look forward to developing specialized courses in areas related to my research. These courses include: (1) ‘Chemical Engineering and Data Science’, which covers high-throughput instrumentation used for chemical synthesis, along with informatics and algorithms used for data analysis. (2) ‘Special Seminar on Scientific Communication’, which is designed to be integrated into the orientation for new graduate students, with the objective of enhancing their proficiency in delivering scientific presentations.

Teaching Experience:

• Unit Operations Laboratory (Illinois ChBE), Teaching Assistant (2021)
• Momentum and Heat Transfer (Illinois ChBE), Teaching Assistant and Guest Lecturer (2020, named to a university-wide “List of Teachers Ranked as Excellent Ranked by Their Students”; part of Illinois “Foundations of Teaching” Certificate Program)
• Graduate Academy for College Teaching (Illinois graduate college new teaching assistant orientation), Guest Lecturer to thirty new TAs (2020).
• Biomolecular Materials Science (Illinois MSE), Teaching Assistant and Guest Lecturer (2019, named to a university-wide “List of Teachers Ranked as Excellent Ranked by Their Students”)

Service and Commitment to Diversity, Equity, and Inclusion:

With a passion deep within for teaching and mentoring, I aspire to spark the curious minds of burgeoning scientists and engage with them in the pursuit of new fundamental knowledge. To this end, I am dedicated to creating a safe, inclusive, and supportive environment that fosters scientific integrity and critical thinking. In graduate school, I was selected as the graduate chair in the Tau Beta Pi Illinois Alpha chapter. I led an initiative to connect with online master students enrolled in the engineering programs at UIUC, both domestically and internationally, and encouraged their participation in our chapter. This program provided support, resources, and advocacy for these remote students, regardless of their geographical location or background. Through a series of social and professional development events, we cultivated a community of engineering students. This program now continues to grow under new student leadership, attracting over thirty participants every semester. I have also shared my experiences with the younger students by participating in panels for the departmental fellowship workshop and undergraduate research symposium at UIUC, as well as by contributing as a reviewer for the Society for Advancement of Chicanos/Hispanics & Native Americans in Science (SACNAS). At Berkeley, I have participated in the Berkeley Girls in Engineering program to offer firsthand experiences of STEM career paths. Currently, I am mentoring an under-represented student from a local community college, aiming to provide mentorship and support to propel the student’s journey in STEM. Through these experiences, I have observed that it is important to help young students understand what STEM is and the career pathways it offers. Looking ahead, I want to seek out new opportunities to organize career-building programs for fostering diversity in STEM.