About
Norelle Daly is Professor at James Cook University (JCU) in Queensland, Australia, and holds an adjunct position at the Institute for Molecular Bioscience (IMB) at the University of Queensland. Her research uses NMR (nuclear magnetic resonance) spectroscopy to determine the precise three-dimensional structures of cyclic peptides — both cyclotides from plants and conotoxins from cone snail venom.
This structural work is not merely descriptive: it is the essential foundation on which rational drug design from these scaffolds is based. Knowing the exact three-dimensional shape of a cyclotide — which loops are exposed, how flexible they are, how they interact with water and membranes — is what tells researchers which positions can accommodate therapeutic sequence insertions without destroying the scaffold's stability or activity. Daly's NMR expertise has made her a central figure in translating cyclotide structural biology into actionable drug design principles.
She has taken the next step of commercialisation by co-founding Paragen Bio — a startup applying disulfide-rich peptide structural knowledge to drug discovery.
Background & Career
Daly built her career at the interface of structural biology and natural product chemistry. Working closely with David Craik's group at the University of Queensland — one of the world's leading centres for NMR-based structural characterisation of peptides — she became one of the foremost experts in applying NMR to the specific challenges posed by cyclotide structures.
Cyclotides present particular structural biology challenges: they are small enough to study by NMR but complex enough, with three disulfide bonds and a cyclic backbone, that interpreting the NMR data requires specialised expertise. Daly developed that expertise over years of collaborative work with the Craik group, producing the detailed structural characterisations of kalata B1 and related cyclotides that are now among the most-cited structures in the field.
Her move to James Cook University — a regional university with particular strengths in tropical and marine biology — gave her access to a rich natural product environment and the opportunity to build her own research programme. Her adjunct position at UQ IMB maintains the collaborative ties that have been so productive over her career.
Alongside her academic work, Daly co-founded Paragen Bio to commercialise the structural knowledge accumulated over years of academic research — applying it to the discovery and development of disulfide-rich peptide drugs.
Key Contributions
- NMR structural characterisation of cyclotides: Central to the structural characterisation of cyclotides using NMR spectroscopy — her work reveals the precise 3D shape of cyclotide loops, backbone geometry, and side-chain orientations, all of which are essential information for drug grafting design. The NMR structures of kalata B1 and other cyclotides that she co-determined are foundational references for the entire field.
- CCK structural plasticity: NMR studies of loop-substituted cyclotide variants contributed to understanding the structural plasticity of the Cyclic Cystine Knot — specifically, which loops can accommodate substitutions or insertions without destabilising the scaffold. This knowledge directly guides the choice of grafting sites in drug design programmes.
- Conotoxin structural characterisation: Applied the same NMR expertise to conotoxins — the disulfide-rich venom peptides produced by marine cone snails, which are another exceptionally rich source of drug scaffolds and lead compounds. Conotoxins are structurally related to cyclotides in their reliance on disulfide-stabilised frameworks, and Daly's dual expertise in both families is unusual and valuable.
- Paragen Bio: Co-founded Paragen Bio — a startup applying the structural knowledge built over years of academic research to commercial drug discovery. Paragen Bio focuses on disulfide-rich peptides as a drug class, leveraging structural biology to guide lead optimisation and selectivity engineering.
- Foundational UQ structural biology programme: Made extensive foundational contributions to the structural biology programme at UQ IMB alongside Craik and other collaborators — helping to build the body of structural data that underpins the entire cyclotide drug design enterprise.
NMR Structural Biology and Drug Design
NMR spectroscopy is one of two major techniques (alongside X-ray crystallography) used to determine the three-dimensional structures of proteins and peptides at atomic resolution. For cyclic peptides like cyclotides, NMR is particularly well-suited: the molecules are small enough for detailed NMR analysis, and — unlike X-ray crystallography — NMR can be performed in solution, capturing the structure in an environment closer to biological conditions.
The structural data Daly has generated answer questions that are directly relevant to drug design. Which loops of the cyclotide scaffold are most exposed on the molecular surface — and therefore most likely to interact productively with a drug target? Which positions tolerate sequence substitution without disrupting the disulfide bonds? How does the structure change when a therapeutic sequence is grafted in? How do cyclotides interact with cell membranes — which is relevant both to their oral bioavailability and to their cell-penetrating potential?
These questions cannot be answered by biochemistry or pharmacology alone — they require the atomic-resolution structural information that NMR provides. Daly's expertise sits at this essential junction between structural science and pharmaceutical application.
Every cyclotide drug grafting project begins with a question that only structural biology can answer: which loop, and which position within that loop, can accept the therapeutic sequence without destabilising the scaffold? The NMR structures produced by Daly and the Craik group provide the atomic-resolution maps that make rational answers to this question possible — turning cyclotide drug design from trial-and-error into structure-guided precision engineering.
Key Publications
Multiple papers co-authored with the Craik lab (UQ IMB).
The foundational NMR structure determinations of kalata B1, circulin A, cycloviolacin, and other key cyclotide family members — establishing the detailed 3D architecture of the Cyclic Cystine Knot and providing the structural reference framework for the entire field.
NMR structural papers on cone snail venom peptides.
Applying the same NMR expertise to conotoxins — revealing the disulfide-stabilised structures of these potent venom peptides and contributing to the understanding of their ion channel and receptor interactions.
Papers examining how loop substitutions and grafted sequences affect the three-dimensional structure of the cyclotide scaffold.
Essential contributions to understanding which modifications are structurally tolerated — directly informing the design of drug grafting projects.
A body of co-authored work spanning more than two decades of collaborative structural research at UQ IMB.
Daly's contributions to the structural biology programme at UQ IMB form part of the scientific foundation on which Australia's position as the world leader in cyclotide research rests.