Supervisors

Professor Frank Vollmer, Department of Phycics & Living Systems Institute, University of Exeter

Professor Irina Vetter, Institute for Molecular Bioscience, University of Queensland

Additional Supervisors:

Professor Mehdi Mobi, The University of Queensland / Australian Insttute for Bioengineering and Nanotechnology

Join a world-leading, cross-continental research team

The University of Exeter and the University of Queensland are seeking exceptional students to join a world-leading, cross-continental research team tackling major challenges facing the world’s population in global sustainability and wellbeing as part of the QUEX Institute. The joint PhD programme provides a fantastic opportunity for the most talented doctoral students to work closely with world-class research groups and benefit from the combined expertise and facilities offered at the two institutions, with a lead supervisor within each university. This prestigious programme provides full tuition fees, stipend, travel funds and research training support grants to the successful applicants.  The studentship provides funding for up to 42 months (3.5 years) for home and international students.

Eight generous, fully-funded studentships are available for the best applicants, four offered by the University of Exeter and four by the University of Queensland. This select group will spend at least one year at each University and will graduate with a joint degree from the University of Exeter and the University of Queensland.

Find out more about the PhD studentships click here

Successful applicants will have a strong academic background and track record to undertake research projects based in one of the three themes of:  Healthy Living, Global Environmental Futures and Digital Worlds and Disruptive Technologies.

The closing date for applications is mid-day Friday June 28th 2024 (BST), with interview to be w/c 29th July 2024 (tbc). The start date is expected to be Monday January 6th 2025.

Please note that of the eight Exeter led projects advertised, we expect that up to four studentships will be awarded.

Supervisors

Exeter Academic Lead: Professor Frank Vollmer

Queensland Academic Lead: Professor Irina Vetter

THEME - Healthy Living

Project Description

Within the theme of Healthy Living, this project aims to understand how biologically active molecules, specifically venom-derived peptides targeting pain pathways, interact with cell membranes and therapeutically relevant transmembrane targets. Understanding these interactions is crucial for the design of novel therapeutics addressing the urgent need for more efficacious, non-addictive analgesic molecules.

Our project introduces a new way of studying these interactions, using a state-of-the-art optical sensor developed at the University of Exeter. This sensor can measure fast changes at the single peptide level without the need for fluorescent labels, enabling us to ‘watch’ how peptides move and change shape near or when bound to membranes.
By combining Exeter's sensor technology with techniques from the University of Queensland, we hope to answer important questions relevant to health and well-being, including how we can rationally modify peptides to fine-tune the function of transmembrane ion channels that are critical for activity of pain-sensing nerves, or how we can modulate peptide-membrane interaction properties to develop new analgesics with prolonged duration of action.
You will first learn how to use the single molecule sensor in Exeter to study the interaction between peptides and other molecules and model membranes, establishing the tool for the first time for sensing single-peptides near membranes. Then, you'll work with experts at the University of Queensland to make specific peptides to identify the molecular determinants of peptide-membrane and peptide-target interactions. You will also use special analysis techniques, including patch-clamp electrophysiology to delineate the structure-activity of peptide ion channel modulators. Outcomes of the new single molecules experiments will be benchmarked against data generated using existing biophysical measurements including nuclear magnetic resonance spectroscopy and isothermal calorimetry.

After completing your studies in Queensland, you will return to Exeter to utilise the sensor on the peptides you prepared and analysed. This will allow you to delve into fundamental questions in the field, investigating the specific properties of peptides and membranes that contribute to peptide-membrane interactions, ultimately determining how these properties can be rationally tuned for development of novel pain therapeutics.
You will collaborate with a team of experts across the globe on an interdisciplinary project that combines state-of-the-art single molecule sensing developed in physics with studies of the pharmacology and toxicology of venom-derived peptide ion channel modulators, which are fundamental model systems enabling us to understand how to modulate signalling of pain-sensing neurons for analgesic drug development. 

The target of many venom-derived peptides that interfere with pain signals are voltage gated ion channels. These proteins consist primarily of transmembrane helices with small extra and intracellular loops. The action of ligands of these receptors are therefore either via the membrane or involves components of the membrane. Untangling the kinetic and thermodynamic contributions of ligand binding in this complex tripartite system is critical for the rational design of novel analgesic drugs.
Currently, researchers use techniques which involve modification with fluorescent labels on molecules or using bulk sensors to study how molecules interact with membranes as well as transmembrane ion channels and receptors critical to function of pain-sensing nerves.  However, these methods have limits in their ability to discern the molecular mechanisms governing interactions between ligands, the plasma membrane, and the therapeutic targets located within the membrane environment.
In particular, these techniques fall short of capturing the transient kinetics and conformational changes inherent in peptide-membrane interactions. To address this gap, our project aims to apply a cutting-edge single-molecule sensor developed at the University of Exeter to study the dynamics of peptide interactions with reconstituted supported lipid membranes to understand how peptide sequence and structure, membrane composition the ionic environment control long lasting peptide-membrane interactions.
The project incorporates three aims:
1. Understanding Molecular Interactions: In collaboration with Prof Vollmer at Exeter, you will first learn to use the single molecule sensor. This involves learning to coat the sensor with lipid bilayers, analysing signals to discern transient and binding interactions, and extracting rate constants to understand the dynamics of peptide-membrane interactions. You will establish this technique for the first time for to study molecular interactions at membranes.
2. Synthesising and Characterising Peptides: In collaboration with Profs Vetter and Mobli at the University of Queensland, you will synthesise peptides and evaluate their biological activity using pharmacological methods including patch-clamp electrophysiology. These studies will be complemented by structural studies using nuclear magnetic resonance spectroscopy to understand the static structures of peptides interacting with membranes.
3. Integration and Analysis: Returning to Exeter, you will apply the single molecule sensing methods to the peptides characterised in Queensland. This involves quantifying how changes in sequence, membrane composition and ionic strength affect interaction kinetics, integrating sensor signals with analysis from Queensland, and studying the role of 2D and 3D diffusion in peptide-membrane interactions.
 
Throughout the project, you will achieve several milestones:

- Learning to operate the single molecule sensor and analysing signals
- Obtaining information on the kinetics and conformational changes in the sensor signals.
- Establishing methodologies to study 2D and 3D diffusion of peptides near membranes.
- Applying advanced sensor measurements and signal analysis to study changes in membrane force and pressure.

Ultimately, your contributions will lead to significant scientific advancements, with results expected to be published in high-impact journals and presented at international conferences and QUEX workshops. Additionally, you will participate in seminars and workshops to develop transferable skills, all within an environment that prioritises equality, diversity, and inclusion, open research practices, and collaborative teamwork.

Entry requirements

Applicants should be highly motivated and have, or expect to obtain, either a first or upper-second class BA or BSc (or equivalent) in a relevant discipline.

If English is not your first language you will need to meet the English language requirements and provide proof of proficiency. Click here for more information and a list of acceptable alternative tests.

How to apply

Apply now

Owing to essential maintenance, SRS will be unavailable between 17:00 BST on Thursday 27th June and 09:00 BST Monday 1st July 2024, which means you are unable to submit an applications during this time.
The application deadline will therefore be extended until 12:00 BST on Wednesday 3rd July.
Please accept our apologies for any inconvenience caused.

You will be asked to submit some personal details and upload a full CV, supporting statement, academic transcripts and details of two academic referees. Your supporting statement should outline your academic interests, prior research experience and reasons for wishing to undertake this project, with particular reference to the collaborative nature of the partnership with the University of Queensland, and how this will enhance your training and research.

Interview notifications date TBC

Please quote reference 5157 on your application and in any correspondence about this studentship.

Summary