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A typical immune response involves a complex choreography of signalling molecules and cells operating in a physical world, where biological behaviour is governed by physical principles such as reaction-diffusion kinetics, nanoscale electrostatics, and statistical mechanics. Immune cells communicate across tightly confined contact zones where receptor spatiotemporal organization, the trafficking of signalling molecules, membrane fluctuations, and intermembrane interactions directly regulate their decisions. Our research aims to bridge the gap between biological observation and the underlying physics and chemistry by developing advanced, high-resolution light microscopy tools. By connecting these high-precision measurements to quantitative models, we aim to uncover the principles that shape immune function in complex biological systems, offering a new perspective that complements traditional genetics and opens new frontiers for drug development and therapeutic intervention.

1. Nanoscale Electrometry: Decoding the Physicochemical Language of the Cell

Our first objective is to pioneer surface-sensitive techniques, such as Metal-Induced Energy Transfer (MIET), to quantify the nanoscale physics of immune signalling. While traditional microscopes show us where molecules are, we develop methods to measure their electrical charge (electrometry) and structural changes (nanometry) at high speed. Through these high-precision measurements, we seek to understand how electrostatic interactions and membrane movements at the nanoscale function as a physical switch for immune responses. This work reveals how the physical state of a membrane can drive or block an immune response, providing a new window into the fundamental rules of how immune cells recognize and respond to threats. 

2. Capturing multi-scale dynamics with next-generation microscopy 

A major frontier in our lab is building next-generation imaging platforms that relax the usual trade-offs between spatial resolution, temporal speed, and field of view. To understand live immune-cell behaviour, we need to observe molecular events across entire cell surfaces and contact zones while still capturing fast dynamics, down to the millisecond timescales on which molecular dynamics and trafficking unfold. Many super-resolution approaches act like “keyholes”: they reveal extraordinary detail, but only over small areas or at acquisition speeds that miss rapid, distributed events.

Immune responses, however, are coordinated across large, crowded interfaces where receptor organisation, membrane rearrangements, and molecular transport occur simultaneously. By engineering high-speed, large-field-of-view biophotonic systems, we aim to capture rare, decisive events at scale, without sacrificing quantitative precision. This enables a shift from studying isolated interactions to mapping immunodynamics holistically, building a physical picture of how molecules, membranes, and cells coordinate decisions in complex environments such as organoids and native tissues.

Selected publications

Leaflet-Specific Structure and Dynamics of Solid and Polymer Supported Lipid Bilayers.

Journal article

Karedla N. et al, (2025), Angew Chem Int Ed Engl, 64

Quantifying biomolecular organisation in membranes with brightness-transit statistics.

Journal article

Schneider F. et al, (2024), Nat Commun, 15

Wide-field optical imaging of electrical charge and chemical reactions at the solid-liquid interface.

Journal article

Mahanta S. et al, (2022), Proc Natl Acad Sci U S A, 119

Graphene-based metal-induced energy transfer for sub-nanometre optical localization

Journal article

Ghosh A. et al, (2019), NATURE PHOTONICS, 13, 860 - 865

Quantifying Microsecond Transition Times Using Fluorescence Lifetime Correlation Spectroscopy.

Journal article

Ghosh A. et al, (2017), J Phys Chem Lett, 8, 6022 - 6028

Simultaneous Measurement of the Three-Dimensional Orientation of Excitation and Emission Dipoles.

Journal article

Karedla N. et al, (2015), Physical review letters, 115

Single-molecule metal-induced energy transfer (smMIET): resolving nanometer distances at the single-molecule level.

Journal article

Karedla N. et al, (2014), Chemphyschem : a European journal of chemical physics and physical chemistry, 15, 705 - 711