PhD in Systems Biochemistry – Investigate self-organized cell polarity and its disruption in disease using in vitro reconstitution and advanced imaging.

About the Project

Project Overview

Cells polarize to divide, migrate and change their shape. Disruptions to this process are hallmarks of disease states such as cancer, where polarity cues become misregulated. This PhD project aims to rebuild the spatial logic of cell polarity from the bottom up, using purified proteins and synthetic membranes, to gain a mechanistic understanding of how normal and transformed cells differ in their ability to self-organize.

You will study how Rho GTPase signalling networks form dynamic activity patterns that direct actin cytoskeleton remodeling. Ultimately, this work will shed light on how changes such as oncogenic mutations in key regulator can perturb the physical logic of cellular organization.

This is a unique opportunity to combine biochemical reconstitution, single-molecule microscopy and synthetic biology to explore the fundamental principles of cell polarity and how they go awry in disease.

Research Aims

• Reconstitute Rho GTPase signaling systems on supported lipid bilayers
• Investigate spatial pattern formation using TIRF microscopy with single-molecule resolution
• Explore Rho GTPase signaling modules from either budding yeast or animal cells
• Probe the influence of oncogenic mutations e.g. Rac1(P29S) on GTPase signaling
• Engineer minimal synthetic signaling systems to test theoretical models of cell polarity

Training & Methodology

You will be trained in a broad range of advanced techniques spanning protein and lipid biochemistry, membrane reconstitution, and quantitative imaging, including:

• Protein purification and lipid reconstitution
• Assembly of liposomes and supported lipid bilayers
• Total internal reflection fluorescence (TIRF) and single-molecule microscopy
• Image processing, kinetic modeling, and data analysis
• Synthetic biology approaches to rewire and test cell polarity systems

This project offers broad exposure to core areas of the emerging field of engineering biology and hands-on experience in building and analysing minimal systems to probe emergent cell behaviours.

Research Environment

The Bieling Lab at King’s College London is an interdisciplinary and collaborative group focused on understanding how cell shape emerges from molecular interactions between membranes, signalling modules and the actin cytoskeleton. We use reductionist, bottom-up approaches and cutting-edge imaging tools to uncover fundamental mechanisms of cell polarity and morphogenesis.

You will be embedded at the Randall Centre for Molecular and Cellular Biophysics, a thriving interdisciplinary community with joint meetings and seminars and part of the wider London Cell Motility research community.

Applicant Requirements

We welcome applicants who:

• Hold or expect to achieve a First or 2:1 (Upper Second Class) degree in Biochemistry, Biophysics, Molecular/Cell Biology, or related disciplines
• Are enthusiastic about protein and lipid biochemistry, in vitro reconstitution, mechanistic biology and microscopy-based discovery
• Have experience in wet-lab biochemistry or imaging (desirable but not essential)

Applicants should demonstrate ambition and passion for fundamental biochemical research, strong analytical thinking, problem-solving skills and a keen interest in molecular mechanisms.

How to Apply

Please send the following to peter.1.bieling@kcl.ac.uk:

• Brief cover letter outlining your motivation
• CV
• Academic transcripts
• Contact details for 2–3 referees

Informal inquiries are welcome.

Funding Notes

Funding Information

This is a fully funded PhD position supported by the Royal Society for a duration of 4 years, covering:

• Home (UK) tuition fees
• Annual stipend
• Research and travel expenses

International students are eligible to apply but would need to cover the fee difference unless separately funded.