BSB PhD Exit Seminar: Establishing a synthetic nanobody yeast-surface display library for its use in structural biology and synthetic biology.

ABSTRACT

Nanobodies are small, stable VHH domains derived from camelid heavy-chain-only antibodies. Compared with conventional IgGs, they are compact, robust and readily engineered, making them valuable for structural biology, diagnostic imaging, biosensors and therapeutics. Historically, nanobody discovery relied on camelid immunisation. Synthetic display libraries provide an animal-free alternative that can generate binders against diverse antigens, including conserved mammalian proteins that may be poorly immunogenic because of immune tolerance. Although phage display is an established method for screening synthetic nanobody libraries, yeast surface display offers several potential advantages. Fluorescence-activated cell sorting enables quantitative selection and, when different antigen states can be distinguished experimentally, the enrichment of binders that recognise specific antigen conformations. In 2018, the Kruse Lab described a yeast surface display platform for selecting high-affinity nanobodies. This project aimed to build on this approach by developing a fast and reliable yeast surface display workflow for nanobody screening. We applied the workflow to a newly designed synthetic nanobody library in which complementarity-determining region diversity was generated using the antibody-specific generative language model IgLM, trained on sequences from the Observed Antibody Space database, and assembled by combinatorial Golden Gate cloning.

BIOGRAPHY

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Jesús is a PhD student in the Brock Lab at RSB. His work focuses on synthetic biology, involving a range of molecular biology techniques centred on expressing nanobodies on the surface of yeast cells. He joined ANU in 2022 after working in clinical trials in Mexico. He completed his Master's in Biochemistry and Bachelor's in Pharmaceutical Chemistry at the Universidad Nacional Autónoma de México (UNAM). Throughout his PhD, he has made great friends and travelled within and outside Australia, both for conferences and for leisure. In his spare time, he enjoys exercising, watching art films, and spending time with friends.