Structural Biology & Biochemistry (SBB) Theme Seminar

When: Thursday 25th June 10-11am
Where: 63-360 (Physiology Building)
Morning tea will be provided afterwards in the MBS secret garden (outside the level 1 tea room)

Title: National Biologics Facility
Speaker: A/Prof. Seth Cheetham

Abstract: The National Biologics Facility (NBF) offers Australian researchers an end-to-end biologics pipeline – from discovery and protein expression through to engineering, process development and clinical-grade manufacture. NBF's capabilities span bacterial, yeast, insect-cell and mammalian expression systems, antibody discovery via phage display, and upstream and downstream bioprocess optimisation, all underpinned by rigorous analytical characterisation. NBF can support researchers by providing high-quality recombinant proteins for structural studies and biochemical characterisation. 

Bio: A/Prof. Seth Cheetham is an ARC Future Fellow and Group Leader at the Australian Institute for Bioengineering and Nanotechnology. He is also the Director of the National Biologics Facility, Australia's leading bio-manufacturing hub. He completed his PhD at the University of Cambridge, supported by the Herchel Smith Research Studentship. Seth is a molecular biologist and geneticist with a focus on biotherapeutics, mRNA and bio-manufacturing. He has authored >30 publications, in some of the most influential molecular biology journals including Science, Molecular Cell, Nature Reviews Genetics, Nature Protocols, Genome Biology and Nature Structural and Molecular Biology. His work has attracted > $85M in competitive funding including eleven years of continuous NHMRC and ARC Fellowship support. In 2021 Seth was awarded the Genetics Society of Australasia Alan Wilton Early Career Award.

Title: Tiny Binders for Big Biological Missions
Speaker: Dr Pie Huda

Abstract: In my talk, I will introduce discovery and engineering of VHHs (nanobodies), the single variable domains of camelid heavy‑chain antibodies. VHHs represent one of the smallest naturally occurring antigen‑binding scaffolds, built on a compact and highly soluble β‑sandwich framework. Their distinctive structural features include an extended and flexible CDR3 loop, the absence of a paired light chain, and a framework adapted for autonomous folding with exceptional stability and refolding capacity. These properties make VHHs versatile building blocks for protein engineering and attractive tools for probing biological systems. Although monoclonal antibodies remain foundational in biotechnology and medicine, their large size limits tissue penetration, slows clearance, and constrains their use in applications requiring rapid or modular responses. VHHs, by contrast, can be expressed efficiently in microbial hosts, diffuse readily through tissues, and maintain structural integrity under conditions that challenge conventional antibody fragments. These advantages have enabled their adoption across diverse areas, including intracellular targeting, biosensing, synthetic biology, conformational trapping of dynamic proteins, and the construction of multivalent or multispecific binding modules. Their small footprint and extended CDR3 also allows them to access recessed or transient epitopes that are structurally inaccessible to larger antibody formats. My work is primarily focused on radiopharmaceutical development of VHHs due to their rapid clearance and high target specificity; however, their small size drives renal filtration and kidney retention which is an important consideration when designing therapeutic constructs. I will briefly outline how these structural and biophysical properties influence their behaviour in vivo and why they matter for applications involving imaging or targeted delivery. Over the past two years, I have established an alpaca‑based VHH discovery platform that generates diverse, high‑affinity repertoires suitable for structural and functional studies. I will introduce this platform and discuss how VHHs can be selected, characterised, and adapted for different research contexts. Finally, I will highlight a range of potential engineering strategies such as framework optimisation, loop grafting, multimerisation, and modulation of size that can be applied to tune VHH properties for applications spanning structural biology, diagnostics, therapeutics, and synthetic protein design.

Bio: Dr Pie Huda obtained her PhD in Biophysics from the University of Copenhagen. She is an EMCR at the Australian Institute for Bioengineering and Nanotechnology (AIBN) and a protein engineer specialising in nanobody (VHH) and antibody‑fragment development for targeted radiotherapy and molecular imaging. She has established Queensland’s first immunisation‑based VHH discovery platform, now supporting multiple internal and external programs focused on precision cancer targeting. Her work has driven the development of innovative nanobody‑based approaches for cancer detection and therapy, with a growing emphasis on radiopharmaceutical applications through her involvement in ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals.