To fully understand biological processes, a comprehensive view is required—one that integrates multidimensional information about the macro-, meso-, and microscopic structure of cells, as well as their dynamics, function, and chemical composition. Since no single imaging technique can capture all of these aspects, correlative microscopy represents the only viable approach to obtaining a holistic understanding of biological processes, including the responses of organisms and cells to environmental or pathogenic factors. Accordingly, recent years have witnessed a growing interest in correlative microscopy, particularly in the form of correlative light-electron microscopy (CLEM), which combines fluorescence and electron microscopy. This technique enables the simultaneous imaging of cellular function (via fluorescence microscopy) and cellular structures (via electron microscopy).

However, one of the main limitations to the broader adoption of CLEM in biological and preclinical research lies in the lack of markers that are simultaneously compatible with both imaging modalities. The FNP First Team project led by Feng, titled “NANOCLEM,” aims to address this limitation. As part of the NANOCLEM project, we will develop a novel type of gold nanoparticle that is compatible with both fluorescence and electron microscopy. The proposed markers will offer functionality beyond that of currently available solutions. They will be capable of controlled cellular uptake and localization within biological structures, due to their small size and tunable hydrophobic and hydrophilic properties.

Our technology will be based on atomically precise gold nanoclusters (i.e., with a precisely defined number of gold atoms and functional ligands), which will provide strong electron microscopy contrast alongside efficient fluorescence. Additionally, these nanoclusters will ensure high stability and excellent reproducibility of labeling procedures for model biological materials.

The scientific partner of the project is Prof. Paul Verkade, Professor of Bioimaging at the University of Bristol (Bristol, United Kingdom), whose laboratory specializes in advanced molecular biology and bioimaging techniques. A pioneer in the field of CLEM, Prof. Verkade has edited several key books on the subject. The significance of his research is evidenced by the impact and reach of his publications: his findings, published in Science, Nature Chemical Biology, Nature Nanotechnology, among others, have been cited over 26,000 times.

The project also includes an industrial partner, Prochimia Surfaces—a company that, for over 20 years, has provided unique surface-coating chemicals (e.g., non-fouling, biocompatible coatings) and offers specialized research services in chemical synthesis and monodisperse nanoparticles, including advanced gold and silver nanoparticles.

The project is scheduled to last four years. In addition to the academic and industrial partners, the research team will include early-career researchers and PhD students, with recruitment to begin shortly.