Biological physics

Achillefs Kapanidis

Gene Machines Group

How do molecular machines find their targets by diffusion, convert thermal fluctuations into action, and organise themselves inside living cells? Can we map the kinetic landscapes connecting molecular sequence to function—and ultimately use these maps to design better molecules?

Our group tackles these questions using single-molecule biophysics, combining advanced fluorescence microscopy and instrumentation with molecular biology, quantitative modelling and AI. We measure diffusion and interactions, resolve transient states and reaction pathways, and connect molecular kinetics to function.

Single molecules at scale—and in context. We recently introduced SPIN-Seq, connecting the kinetic behaviour of individual molecules directly to their DNA sequence (Hazra et al., Nature Communications, 2026; Kapanidis et al., Science, 2026). We are developing large-field-of-view instruments to move from thousands towards ~100,000 single molecules per field of view, while retaining rich molecular information and sequence identity; complementary approaches extend this to millions of reaction compartments. These datasets will enable systematic maps of molecular interactions and kinetics, revealing general rules, rare behaviours and hidden patterns inaccessible to smaller experiments.

From molecules to living cells. We track individual molecules inside bacteria, using their diffusion, interactions and spatial distributions to understand cellular organisation (El Sayyed et al., Molecular Cell, 2024). Our work is revealing a dynamic bacterial nucleolus-like hub, whose material properties, phase behaviour and non-equilibrium organisation raise fundamental questions—and may expose new antibiotic targets.

AI: from data to prediction and design. We develop AI methods such as DeepTRACE to learn molecular actions from single-molecule trajectories (Pambos et al., Communications Biology, 2026), and explore deep learning for massive smFRET datasets (Beigzadeh et al., Current Opinion in Structural Biology, 2026). We also use AI for antimicrobial-susceptibility testing (Zagajewski et al., Communications Biology, 2023) and rapid bacterial identification. Next, we aim to train models that uncover sequence–structure–dynamics–function relationships, progressing from hidden patterns to predictive rules and ultimately AI-guided molecular design.

Projects span next-generation instruments, molecular mechanisms, cellular organisation and AI, with routes towards new diagnostics, antibiotic targets and therapeutics. We strongly encourage innovation and entrepreneurship, building on our track record of translating technologies beyond the laboratory, and welcome students from physics, biophysics, physical chemistry, biochemistry, engineering and computing.

Richard Berry

Nature DID invent the wheel, at least 3 times! The bacterial flagellar motor is 50 nanometres across, spins at over 100,000 rp. driven by electric current, and propels swimming bacterial cells. ATP-synthase is even smaller, about 10 nm across, consists of two rotary motors coupled back-to-back, and generates most of the ATP – life's 'energy currency – in most living organisms. We are trying to discover how these living machines work. We develop and use a range of methods in light microscopy including ultra-fast particle tracking, magnetic and optical tweezers and single-molecule fluorescence microscopy. Current projects in the lab: measurement of stepping rotation and mechano-sensing in flagellar motors, synthetic biology using ATP-synthase,single-molecule fluorescence microscopy of protein dynamics in bacterial motility and chemotaxis, high-torque magnetic tweezers, templated assembly of flagellar rotors using DNA nanotechnology scaffolds (collaboration with Turberfield group). More information on Oxford Molecular Motors can be found here.

Stephen Tucker

Almost every single process in the human body is controlled at some level by electrical signals, from the way our hearts beat, the way our muscles move, to the way we think. These electrical signals are generated and controlled by a family of proteins called 'ion channels' which reside in the membrane of every living cell and which act as 'electrical switches' to control the selective movement of charged ions like potassium (K⁺) and Sodium (Na⁺) into and out of the cell.

Work in our lab uses a range of multidisciplinary approaches (molecular biology, protein biochemistry, electrophysiology, single-molecule fluorescence, molecular dynamics and cryoEM) to study the structure and function of these channels. We have a range of projects available to people with physics, engineering, computing, biochemistry and physiology backgrounds.

We currently have a DPhil project available to investigate how the unusual behaviour of water within the nano-sized pore of an ion channel influences its behaviour. This project would suit someone with a computational background and/or programming skills as it involves development of software to annotate membrane protein structures. Also, we have projects available to work on the structural determination of ion channel drug binding sites and channel gating mechanisms using CryoEM as well as electrophysiological approaches to study ion channel gating (including macroscopic and single channel recording techniques).

Nynke Dekker

During our lifetimes, we copy approximately a lightyear’s worth of DNA, and how the different components of the molecular machinery (the replisome) work together to achieve this successfully is an area of highly active research.  Here, you will take on the exciting challenge of understanding the dynamics of DNA and chromatin replication by purifying, reconstituting, and studying the activity of eukaryotic replisome at the single-molecule level. You will examine replisome composition, replisome motion dynamics, and the interplay between these two quantities; and examine how these change in the context of chromatin or obstacles on the DNA. To do so, you will employ a combination of novel biophysical instrumentation (e.g. fluorescence imaging, single-molecule force spectroscopy, microfluidics, cryo-electron microscopy) and biochemical approaches (protein purification, biochemical assays, DNA sequencing). You will analyze the resulting datasets using biophysical modelling, interact with collaborators in molecular biology and biochemistry at the University of Oxford and at highly regarded institutions elsewhere in the United Kingdom. In doing so, you will publish high-quality scientific papers to advance this exciting field and ultimately, its impact on biomedical applications

Dominika Gruszka

Life is perpetuated through countless rounds of cell division – the human body alone undergoes approximately 10¹⁶ divisions over a lifetime. Each division requires the precise duplication of the entire genome, followed by faithful segregation into two daughter cells. A cell’s identity and function are determined by its specific gene expression programme, and its ability to stably maintain and transmit this program across divisions is known as epigenetic memory. Epigenetic memory is a fundamental biological process that governs how cellular identity and function are inherited in both healthy tissues and in contexts such as ageing, cancer, and other diseases. Yet, despite its importance, the molecular mechanisms that sustain epigenetic memory remain poorly understood.

Within the nucleus, DNA is wrapped around histone proteins to form chromatin – a dynamic structure that packages and regulates access to genetic information. Epigenetic information is encoded in histones through chemical modifications and specific histone variants, collectively referred to as the histone code. This code influences chromatin structure and controls which genes are turned “on” or “off,” thereby forming the molecular foundation for epigenetic memory. However, it remains unclear how histone-based information is faithfully preserved during DNA replication, when both DNA and histones must temporarily dissociate to allow genome duplication. The Gruszka Lab combines state-of-the-art single-molecule imaging with chemical, physical, and computational approaches to explore the fundamental principles of chromatin structure, dynamics and epigenetic inheritance. We offer a range of DPhil projects – experimental, computational or hybrid – tailored to each candidate’s skills and research interests. Our highly interdisciplinary environment welcomes students from diverse backgrounds, including biochemistry, chemistry, physics and computer science. Interested candidates are warmly encouraged to contact Dominika Gruszka to discuss available opportunities