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Biophysicist in Profile

Chan Cao

Chan Cao

November 2023 // 1071

Chan Cao grew up in Yulin in China’s Shaanxi province. She displayed curiosity about the natural world from a young age, becoming the first in her family to pursue a scientific career. Her enthusiasm for science was especially sparked by her high school teacher, Zengguang Li, who introduced her to the beauty of physics. Throughout her university years, Cao found herself fully immersed in a realm where experimentation and exploration became her life's passion. Pursuing her undergrad­uate studies in Applied Chemistry at East China University of Science and Technology (ECUST) allowed her to dive headlong into hands-on physical and chemical experiments. This fervor for practical science ultimately charted her course toward a distinguished career in bioanalysis.

Cao continued her doctoral studies at ECUST, where she focused on analytical chemistry due to her fascination with the characterization of biomolecules. During her PhD studies, she achieved a breakthrough by using aerolysin as a nanopore sensor for DNA analysis, slowing down DNA translocation by a factor of 1,000 compared to previous methods. This nanopore is now widely adopted in numerous research groups.

To delve deeper into the molecular mechanisms of aerolysin nanopores for molecular sensing, Cao then pursued a postdoc­toral position at the Laboratory for Biomolecular Modeling, led by Matteo Dal Peraro, at École Polytechnique Fédérale de Laus­anne (EPFL) in 2017. This was supported by a Marie Sklodows­ka-Curie fellowship. Through a combination of experiments and molecular dynamics simulations, Cao and her colleagues systematically explored DNA interactions with a nanopore and pinpointed two critical sensing regions within the aeroly­sin pore lumen. Furthermore, they also characterized a large range of pore mutants, unraveling the intricate relationship between aerolysin’s structure and its sensing capability. Their engineered variants exhibited enhanced resolutions, proving proficient in reading both DNA and, notably, peptides of diverse natures.

“I faced several challenges simultaneously when I started the postdoc at EPFL,” recalls Cao. “First, I needed to acquire programming skills, a significant shift from my wet-lab-based background. Concurrently, I wrote several research proposals to secure funding for my new ideas. This was all done while I was adapting to the Swiss research environment.” Overcoming these differences demanded patience, an open mindset, and steady determination.

Cao’s pioneering work was recognized, and she was awarded a prestigious Swiss National Science Foundation PRIMA grant, allowing her to establish her independent research group at EPFL in 2020. During this time, Cao further improved the reading accuracy of nanopores and achieved single-nucleobase resolution by eliminating the influence of neighboring bases. Moreover, she explored the potential of engineered aerolysin nanopores in two domains: 1) molecular data storage, demon­strating the sequencing of macromolecular analytes with single-bit resolution without motor proteins in a nanopore platform, and 2) biomarker detection, simultaneously distin­guishing diverse protein post-translational modifications in alpha-synuclein, which is a disease-associated protein, as potential biomarkers for neurodegenerative diseases.

Nominated Assistant Professor at the University of Geneva in 2023, Cao continues to advance her research and explore new possibilities in bioanalytical chemistry and biophysics. Drawing from her experiences and past challenges, she deepens her understanding of the fundamental building blocks of life and strives for transfor­mative advances in medicine and engineering through ongoing innovation and interdisciplinary collaboration. Her future involves adapting her nanopore approaches to study biomolecules be­yond DNA, such as proteins and glycans, opening up exciting possibilities.

Outside of work, Cao immerses herself in nature through regular hiking and swimming in Switzer­land's lakes. She also enjoys painting and cook­ing, finding fulfillment in these creative pursuits.

Cao is both a prolific researcher and a dedicated advocate for science outreach and communi­cation. Throughout her career, she has actively engaged with the broader scientific community and the public to share the excitement of bio­physics and analytical chemistry. Her contribu­tions include organizing conferences, serving on doctoral program committees, and participating in teaching and mentoring, all with the aim of benefiting the next generation of scientists.