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Department of Pharmacology



Information on all current research studentships vacancies can also be found on the Jobs page of our website. New studentships will be added soon.

Functional and Pharmacological Characterization of Insect Inositol-1,4,5-triphosphate Receptors

CTP - Sustainable Agricultural Innovation (SAI) funded PhD Studentship - To start October 2024


The delivery of novel means of protecting crops against damage caused by insect pests is essential for sustainable agriculture. There is both a need to identify new protein targets and to better resolve the molecular interactions between target proteins and their effector ligands to tackle the spread of target-based resistance. The recent development of crop-protection products which deliver their insecticidal effects by modulating ryanodine receptor (RyR) function has highlighted the potential of intracellular Ca2+signaling as a target for insect control.  The success of these products, which are based on a class of insecticides collectively known as diamides, has been limited by the surprisingly rapid emergence of target-based resistance in the field.  The RyR is a huge protein, so it is conceivable that structural variants with high resistance potential were already occurring naturally in insect pest populations before these populations were ever exposed to diamides.  The IP3-receptor is significantly smaller in size yet shares similarities with RyR in terms of structure, function, and regulatory mechanisms.  In this project multidisciplinary project we will combine molecular biology, cell biology, bioinformatics and electrophysiology with an aim to generate tools and methods that will enable some key questions relating to the potential of IP3Rs as novel insecticide targets to be addressed.


1. Develop a cell-based assay to study the IP3R from a pest insect such as Plutella xylostella. (0-15 months) We have access, within the Cambridge Cell Signalling group, to a HEK293 cell line which is null for the three human IP3R (HEK-IP3R null). We will clone the insect IP3R into pcDNA3.1 and express this in the HEK-IP3R null cell line and assay for histamine/carbachol induced Ca2+ release. Both histamine and carbachol activate Gq-coupled receptors to stimulate IP3 production. Using fluorescent dyes (furo-8 etc) we will assay insect IP3R activity. Once the system has been successfully established, a HEK cell line will be developed that expresses the insect IP3R stably within the cell. Compounds known to target the RyR will then be assayed for selectivity against the IP3R.

2. SDM pharmacology studies to identify residue positions in druggable sites representing key differences between species. (12-30 months). We will use bioinformatics to compare sequences from target and non-target organisms to identify residues with potential for achieving target selectivity. Key sites will be mutated within the receptors which will be expressed in the HEK-IP3R null cell line and assayed as described in 1. In silico modelling, docking and atomistic molecular dynamic (MD) simulations will be performed to probe the IP3R binding sites and compared to human IP3Rs.

3. Assess the potential for targeting the insect IP3R. (18-30 months). Using the cell lines developed in 1, we will screen a series of compounds (supplied by Syngenta) against the insect IP3Rs. This will enable the development of new chemical scaffolds to target the IP3R.

4. Electrophysiological investigations of insect and vertebrate IP3Rs. (24-48 months) We will express tagged versions of insect and vertebrate IP3Rs to enable electrophysiological (at single channel level) investigations using nuclear (on-nucleus or excised-mode) patch-clamp recording, or even pull-down purification and reconstitution in planar lipid bilayers. Such methods could be used to characterise basic biophysical properties of insect IP3R relative to a mammalian reference (e.g., rat IP3R1) and may allow further profiling of active compounds (tested in 2 and 3) in terms of their species selectivity or involvement in mechanisms of Ca2+ regulation including IP3-dependent and IP3-independent Ca2+inhibition, regulation by ATP, channel inactivation etc. We will also consider co-expression of an insect IP3R in HEK-IP3R null cells with a Ca2+-activated Cl-- channel such as anoctamin-1 to report IP3R-mediated calcium release. Such cells would be compatible with the whole-cell patch-clamp method which could provide a relatively straightforward way to investigate the effects of compounds. It should also be possible to explore the effects of endogenous modulators to some degree by altering the concentrations of Ca2+, Mg2+and ATP in the pipette solution.

The Dept. of Pharmacology at Univ. Cambridge is a world-leading authority on cellular calcium signalling and has broad expertise in techniques for visualising the contributions of proteins involved in Ca-signalling pathways at the sub-cellular and molecular level. Extending this experience to the study of insect IP3Rs would provide key insight into the role of these ion-channels in the response to insecticides and evaluate their potential as insecticide targets.


Contact Prof. Graham Ladds (Email: for an informal discussion on the research content of this PhD.

This studentship will begin in October 2024. The successful candidate should have (or expect to have) an Honours Degree (or equivalent) with a minimum of 2.1 in Plant Science, Applied Statistics, or other related science subjects. Students with an appropriate Masters degree are particularly encouraged to apply.

We welcome UK, EU, and international applicants. Candidates whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. Candidates should check the requirements for each host organization they are applying to, but IELTS 6.5 (with no component below 6.0) or equivalent is usually the minimum standard.

This studentship is for four years and is fully funded in line with UKRI-BBSRC standard rates. These were for 2023/24, an annual maintenance stipend of £18,622, fee support of £4,596, a research training support grant of £5,000 and conference and UK fieldwork expenses of £300.

To be classed as a home student, candidates must meet the following criteria:

  • Be a UK National (meeting residency requirements), or

  • Have settled status, or

  • Have pre-settled status (meeting residency requirements), or

  • Have indefinite leave to remain or enter

If a candidate does not meet the criteria above, they would be classed as an international student and must demonstrate the ability to meet the supplement in fees required for an international student.

Anyone interested should complete the online application form before the deadline of 7th January 2024. Interviews will be held during January 2024.

Please contact, or see the CTP-SAI website (, for further application details.

Artificial intelligence design of antibody modulators of GABA-A receptors

BBSRC-DTP Targeted Studentship - To start October 2024

We seek a motivated PhD candidate to lead a multidisciplinary project at the forefront of precision pharmacology in the biochemistry of the central nervous system. Gamma-aminobutyric acid type-A (GABA-A) receptors play key roles in inhibitory neurotransmission and are targets of several drugs. Different subtypes of GABA-A receptors contribute to distinct neurological processes such as cognition, anxiety, addiction, sedation, motor coordination, and nociception. However, current small molecule tools lack sufficient selectivity to unravel the distinct contributions of GABA-A subtypes. In contrast, antibodies offer improved specificity and open new avenues for biomedical research.

This PhD project is a joint between the Sormanni lab (Chemistry) and the Miller lab (Pharmacology). It builds on the Miller lab's ground-breaking work in developing nanobody modulators against GABA-A receptors (1). Cryo-electron microscopy structures provided insights into the modulators' mechanisms of action and can serve as an excellent starting point for computational engineering approaches (2). The goal is to further develop and employ artificial intelligence (AI) antibody-design strategies available in the Sormanni lab (3, 4) on receptor-antibody structures to “jump” specificity between subtypes and create new pharmacological tools. In this way, novel dual-subtype selective modulators will be generated for the first time. Computational outputs will be tested, ratified, and studied using biophysical techniques, electrophysiology, and cryo-electron microscopy. By joining this project, the student will have the opportunity to contribute to the establishment of new antibody design strategies and the creation of novel pharmacological tools for neuroscience research.

(1)    Kasaragod…Miller. Nature. 2022.
(2)    Miller…Aricescu. Biorxiv. 2018
(3)    Aguilar Rangel…Sormanni. Science Advances. 2022.
(4)    Ramon…Sormanni. Biorxiv. 2023 (Nature Machine Intelligence under review)

For queries or should you wish to discuss this opportunity further please contact Dr Pietro Sormanni (Dept Chemistry) - or Dr Paul Miller (Dept Pharmacology) –

The application process is expected to open in Sep 2023.
To apply please visit:

Targeting chronic pain using new pharmacological approaches against sodium channels
MRC-DTP PhD studentship with industry partner Metrion Biosciences - To start October 2024
Chronic pain includes common conditions such as osteoarthritis, lower back pain and irritable bowel syndrome, and is a leading cause of disability worldwide. Chronic pain diminishes quality of life and in the UK 8 million adults experience disabling chronic pain at a cost of £10 billion per year to the UK economy.  There is urgent need for safe effective chronic pain treatments because over 50 % of patients require daily opioids which have serious side effects, causing physical and psychological dependence and excess mortality.
Voltage-gated sodium channels, Nav 1.7, 1.8 and 1.9 have emerged as primary targets for the treatment of chronic pain but small molecules identified so far against Navs often have limited subtype specificity, short occupancy times, inappropriate pharmacokinetics, and toxicity, hampering clinical translation.
This project will focus on novel pharmacological approaches to target Navs for the treatment of chronic pain. This will combine expertise from the Miller lab in small molecule, toxin and antibody modulation of ion channels (Nature, 2022) and expertise in the Ladds lab in bioluminescence resonance energy transfer (BRET) to understand G-protein coupled receptor pharmacology (Wall et al., 2022).
This project will develop the technique of BRET as a new strategy to observe small molecule, toxin and antibody modulation of Navs. Techniques will include protein production of antibodies, toxins and Navs, expression of channels in cells, pharmacological BRET assays, and the potential for cryo-EM to observe ligand-receptor interactions at atomic resolution. During the course of the project a placement at Metrion Biosciences in Cambridge will offer the chance to perform ligand screening against Navs using automated or manual electrophysiology and/or BRET assays. This work will empower therapeutic targeting of Navs to treat chronic pain.
Kasaragod VK...Miller. Nature 2022 PMID:35140402
Wall MJ…Ladds…Frenguelli. Nat Commun 2022 PMID:35851064
For queries or should you wish to discuss this opportunity further please contact Dr Paul Miller (Dept Pharmacology) – The application process is expected to open in October 2023 - check to see if it's open yet. Funding is for 4 years covering UK/overseas fees and provision of a stipend with industry supplement.

Aptamers as a tool for targeting bacterial outer membrane proteins

BBSRC DTP PhD studentship - To start October 2024

In the Mela laboratory, we have combined DNA nanostructures and aptamer nanotechnology to create bacteria-specific delivery vehicles, with the potential to deliver a multitude of active compounds to bacterial targets. We will now build on this work, to develop novel, highly sophisticated DNA-based systems for targeted and controlled antimicrobial delivery and simultaneous blocking of bacterial receptors. The aim of this PhD project is the selection of aptamers (oligonucleotides that bind to specific target molecules with high affinity) that can bind specific surface proteins on particular bacterial strains, to maximise the specificity and efficiency of drug delivery. The focus will be on targeting aptamer-derivatised DNA nanostructures to two specific surface proteins that are crucial to the survival of MRSA and P. aeruginosa. On MRSA, the target proteins will be fibronectin-binding proteins A (FnBPA) and B (FnBPB). These proteins mediate adhesion of MRSA to the extracellular matrix and are involved in MRSA invasion of host organisms and in the formation of biofilms. The target proteins on P. aeruginosa will be pseudomonas haem uptake (Phu) and haem assimilation (Has) receptors. The Phu and Has receptors are crucial for P. aeruginosa, as they facilitate the sourcing of iron — an essential micronutrient for the survival and virulence of Gram negative pathogens — from haem. Once the best performing aptamers are selected, we will explore their potential as a tool against antibiotic resistance. We will assess the aptamers for their potential to drive the binding of nanostructures on the bacterial surface and as pharmacologically-relevant molecules, with the ability to disrupt crucial bacterial functions.

For more information on the group leader and their research:

Research area: DNA nanotechnology, targeted delivery, aptamer selection, microbiology, microscopy

BBSRC DTP main strategic theme: Transformative technologies

BBSRC DTP secondary strategic theme: Bioscience for an integrated understanding of health

For queries or should you wish to discuss this opportunity further please contact Dr Ioanna Mela (Dept Pharmacology) –

To apply please visit: