Figure 1: In the Deo group, we design, synthesise and study the properties of fluorescent probes before their implementation in biological systems. Work in the lab involves mainly synthetic chemistry and protein engineering, as well as spectroscopy and microscopy techniques.
Figure 2: Example of fluorescent tools being developed in the lab. (a) Fluorogenic labels become brightly fluorescent upon binding to their protein target, guaranteeing low unspecific background in cells. (b) Fluorescent indicators show an increase in emission upon binding to a specific analyte. (c) Photoswitches whose fluorescence can be modulated by irradiation with light are of particular interest for super-resolution microscopy.
The Deo group develops enhanced fluorescent reporters for light microscopy by combining synthetic chemistry and protein engineering.
Previous and current research
The fundamental challenge of modern biology is to unravel how biomolecules regulate the complex functions of cells. Fluorescence microscopy has become a powerful tool to decipher the molecular underpinnings of biological systems, as it allows monitoring of biochemical details inside cells with high spatial and temporal resolution. However, the investigation of many intricate cellular processes is only beginning and new discoveries will require more effective fluorescent reporters. Our group aims at developing novel chemical tools to push the frontier of fluorescence imaging and allow interrogation of biological systems at the molecular, cellular and organismal levels.
We design and build innovative probes by combining the superior fluorescence properties of synthetic fluorophores with the specificity of genetically encoded protein scaffolds. This approach, at the interface of synthetic chemistry and protein engineering, has the promise to overcome many limitations of currently available reporters. As tool-builders, we work in close collaboration with microscopists and biologists who implement our tools to ultimately increase our understanding of complex cellular functions.
Future projects and goals
Our group aims to further explore new mechanisms for the development of bright, modular and specific fluorescent tools for biological imaging. Future research interests include:
Novel fluorogenic labeling strategies:
We will develop novel strategies for fast and specific labelling of biomolecules. We will focus on the design of fluorogenic markers, which show no fluorescence signal until bound to their target, ensuring low background. This work will expand the available portfolio of targetable dyes to allow simultaneous visualisation of multiple biomolecules within cells.
Hybrid approaches for fluorescent indicators:
Indicators where the fluorescence signal is modulated by binding of a specific analyte are fundamental tools for monitoring biological processes. Using a ‘chemigenetic’ (both chemical and genetically encoded) approach, we will generate high-performing sensors for a variety of cellular analytes, enabling multicolour monitoring of subcellular signalling with high potential for in vivo imaging.
Photoswitchable fluorophores for super-resolution microscopy:
Fluorophores that can be activated with light are key components for super-resolution imaging, enabling the visualisation of biomolecular structures below the diffraction limit. We will develop photoswitchable systems using robust synthetic switches and fluorophores, resulting in bright and photostable reporters that are particularly promising for multiple super-resolution microscopy techniques.