2026-27 Project (Török & Kopach)

Identifying the Piezo2 receptor function and its role in the brain.

SUPERVISORY TEAM

Supervisor

Professor Katalin Török at City St George’s
School of Health & Medical Sciences, Department of Molecular and Biomedical Sciences
Email: ktorok@sgul.ac.uk

Co-Supervisor

Dr Olga Kopach at City St George’s
School of Health & Medical Sciences, Department of Molecular and Biomedical Sciences
Email: okopach@sgul.ac.uk

PROJECT SUMMARY

Project Summary

This PhD project aims to explore the function and regulatory role of mechanosensitive Piezo2 channels in orchestrating neuronal excitability and maintaining brain network activity under normal and pathological conditions. While the mechanosensitive transmembrane ion channel Piezo2 is well recognised as vital for mechanosensation and pain perception in the peripheral nervous system, its role within the central nervous system remains largely enigmatic. The expression and activity of Piezo2 channels in brain cells, including neurons, astrocytes, and gliovascular units, are not fully understood. This research will elucidate how Piezo2 channels function across nerve cells types within brain tissue in control and pathological conditions. Ultimately, this research aims to identify the role of Piezo2 channels as potential therapeutic targets for modulating brain activity in health and disease.

Project Key Words

Neurons, live-cell imaging, mechanosensation, astrocytes

MRC LID Themes

Translational and Implementation Research
Global Health
Health Data Science

Skills

MRC Core Skills

Quantitative skills
Interdisciplinary skills
Whole organism physiology

Skills we expect a student to develop/acquire whilst pursuing this project:

Throughout the course of this PhD, the student will gain a comprehensive range of technical, analytical, and professional skills essential for independent research. Core training will be in advanced fluorescent imaging (high-resolution live-cell confocal imaging). Complementing this, the student will acquire expertise in immunostaining approaches in thick tissue. The student will also develop strong foundations in molecular and genetic methods, such as transfection and manipulation of optical sensor expression in brain tissue. These experimental approaches will be coupled with training in sophisticated quantitative analysis, image processing, and statistical methods. This all will equip the student with a broad range of skills applicable across biomedical research. Beyond laboratory expertise, the project will help to build interdisciplinary thinking at the intersection of neuroscience, cell biology, biophysics, and mechanobiology. In addition, the student will strengthen skills in scientific writing, oral presentation, project management, and teamwork, ensuring readiness for careers in academia, industry, or translational research.

Routes

Which route/s are available with this project?

1+4 = No
+4 = Yes

Possible Master’s programme options identified by supervisory team for 1+4 applicants:

Not applicable

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? No

Location & Travel

Students funded through MRC LID are expected to work on site at their primary institution. At a minimum, all students must meet the institutional research degree regulations and expectations about onsite working and under this scheme they may be expected to work onsite (in-person) more frequently. Students may also be required to travel for conferences (up to 3 over the duration of the studentship), and for any required training for research degree study and training. Other travel expectations and opportunities highlighted by the supervisory team are noted below.

Day-to-day work (primary location) for the duration of this research degree project will be at: City St George’s – Tooting campus, London

Travel requirements for this project: None

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

Minimum standard institutional eligibility criteria for doctoral study at City St George’s
Applicants are expected to hold a first degree in neuroscience, clinical neuroscience, or physiology.
Excellent understanding of cellular neuroscience and basic knowledge of biophysics and/or cellular biology is mandatory. Other relevant skills will be taught during the project.
Prior experience in electrophysiology and/or fluorescent imaging is highly recommended.

Other useful information

Potential Industrial CASE (iCASE) conversion? = No
CSG change of supervisory role = The supervisory team may switch roles over the course of the studentship award.

PROJECT IN MORE DETAIL

Scientific description of this research project

Mechanotransduction is a fundamental and evolutionarily conserved process found in all cells that allows organisms to rapidly convert mechanical forces into cellular responses by generating chemical or electrical signals. This process is mediated through the mechanosensitive ion channels, specifically the PIEZO family of transmembrane ion channels. The PIEZO family includes Piezo1 and Piezo2 channels, discovered in 2010, both of which are the most structurally unique and physiologically important. Piezo2 is well recognised as a key mediator of mechanosensation and pain processing in the peripheral nervous system. However, its expression, distribution, and function in the brain remain largely enigmatic. This PhD project is designed to address this critical knowledge gap by systematically investigating Piezo2 channel expression in the brain, as well as the channel’s contribution to neuropathological conditions.

The project has three main objectives:

to identify the cellular and regional expression profile of Piezo2 in the brain
to examine whether Piezo2 expression changes across the lifespan, and
to explore the contribution of Piezo2 to neuronal vulnerability, excitotoxicity, and network disruption under pathological conditions, particularly after acute ischaemic injury.

To achieve these aims, a multimodal methodological framework will be employed. High-resolution imaging techniques with immunostaining will be applied to map the distribution of Piezo2 channels across different cell types, such as various neuronal subtypes, astrocytes, glial populations, and gliovascular units in brain tissue. Age-dependent changes in Piezo2 expression will be investigated using brain tissue samples from laboratory animals (rodents) at different developmental stages and ages. Functional studies will then be conducted using acute brain slices and organotypic tissue preparations subjected to experimental ischaemia, allowing to examine how Piezo2 channels contribute to neuronal vulnerability and ischaemic brain damage. Importantly, the project offers a unique opportunity to utilise a novel genetically encoded optical sensor specific to Piezo2 channels. This innovative tool will enable live-cell functional monitoring of Piezo2 activity with high spatial and temporal precision, advancing mechanistic insights into Piezo2-mediated mechanosensitivity in organised brain tissue. This approach is expected to pave the way for new functional studies of Piezo2 channels in a native 3D tissue environment.

Methodologically, the project will combine cutting-edge optical techniques with a range of advanced neuroscience approaches to work with native brain tissue. Logistically, the project will be conducted in a collaborative environment, drawing on the expertise of neuroscientists and cellular and molecular biologists with extensive experience in high-level research and student supervision. The candidate will receive training in advanced neuroscience methodologies, optical and genetic tools, as well as data analysis pipelines. Ultimately, this research aims to identify the role of Piezo2 channels as potential therapeutic targets for modulating brain activity in health and disease.

Additional information from the supervisory team

The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.

Török & Kopach Recording

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Full list of available projects: MRC LID Projects
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