Regulation of neuronal excitability using IgG targeting of ion channels and GPCRs
Academic Supervisor: Prof. Ewan St. John Smith
Industrial Partner: Maxion Therapeutics
Bioscience South Cambridge doctoral training Partnership (BioSCaPe) is a transformative PhD programme designed to create the bioscience leaders of tomorrow. Based in the heart of the world-leading Cambridgeshire bioscience cluster, BioSCaPe offers an unparalleled opportunity to combine cutting-edge research with entrepreneurial and leadership skills. Studentships are hosted in one of the four world-leading research organisations—the Babraham Institute, Wellcome Sanger Institute, MRC Laboratory of Molecular Biology, and the University of Cambridge—and developed with major industry partners including AstraZeneca, Illumina, Alloy Therapeutics, and other industry partners, alongside the Babraham Research Campus and its network of bioscience companies.
Starting October 2026, a 4-year Research Studentship will be available leading to a University of Cambridge PhD degree in the laboratory of Prof Ewan Smith.
Project Details
Our ability to detect internal and external stimuli depends upon specialised sensory neurons that are tuned to specific stimuli. When activated, sensory neurons transmit signals to the central nervous system where processing occurs, and an appropriate response generated. To fulfil their complex function, neurons deploy two major classes of receptor: ion channels and G protein-coupled receptors (GPCRs). Ion channels are transmembrane receptors that can be activated by multiple stimuli and play critical roles in signal detection and propagation, whereas GPCRs primarily function at nerve terminals and synapses, being involved in stimulus detection and neurotransmission.
Considering their critical roles in regulating neuronal function, it is unsurprising that numerous therapeutics target neuronally expressed ion channels and GPCRs. Recent years have seen much interest in longevity but understanding how to support extended health span is more important than simply extending lifespan. As we age, like many organ systems, the nervous system falters in its function.
Increasing knowledge of the mechanisms by which neuronal activity is regulated by ion channels and GPCRs is critical to developing neuroprotective and neurotherapeutic agents. Maxion Therapeutics have developed transformative technology that fuses naturally occurring toxins with antibody frameworks, KnotBody® technology that combines the selectivity and potency of evolution with the half-life and manufacturability of antibody technology. Specifically, Maxion Therapeutics have developed KnotBody molecules, which can specifically target a wide range of ion channels and GPCRs that regulate neuronal activity, from acid-sensing ion channel 1a, which is involved nociception and neurotransmission, through to adenosine GPCRs that regulate sensory neuron activity and sleep/wake state.
This collaborative project with the laboratories of Prof. Graham Ladds with Prof. Ewan St. John Smith (GPCR and neurophysiology expertise, respectively) will enable comprehensive in vitro through to in vivo characterisation of KnotBodies that have potential to regulate neuronal activity. Initial work will be conducted in the Ladds Lab to determine potency, selectivity, signalling bias etc. of different KnotBodies in cell lines overexpressing ion channels / GPCRs of interest. Only efficacious and potent KnotBodies will progress through to testing in the Smith Lab using primary neuronal tissue from mice, an approach aligning with the Reduction goal of the 3Rs because primary neuronal testing will only be conducted on those KnotBodies passing through rigorous cell line characterisation. Where the desired activity is preserved in primary neurons, KnotBodies will progress to in vivo testing, the Smith Lab having experience with a wide range of behavioural assays, as well as the histological methods required for post-mortem assessment of target engagement.
As well as learning a plethora of in vitro and in vivo techniques, the student would also benefit from skills learned during the placement at Maxion Therapeutics; from protein expression, binding and functional assays including ELISA, flow cytometry, automated patch-clamp electrophysiology, and state of the art protein engineering techniques using phage and/or mammalian display technology.
In summary, this project will comprehensively characterise different KnotBodies, technology that could provide tools that transform how neurophysiology is studied, as well as be applied to treating conditions associated with ageing.
Keywords: Ion channel, G protein-coupled receptor, electrophysiology, nociception, behaviour
Application deadline: Thursday, 26th February 2026