Technology Platforms

CLEM Core

Edoardo D’Imprima

Head of CLEM Core

The CLEM Core aims to leverage electron microscopy to study diseases at the interface between basic and clinical research, in collaboration with industry partners, universities, and the Hospital. We believe in the power of electron microscopy imaging to improve people’s lives by studying how diseases develop at tissue, cellular, and molecular levels.

The challenge

Biological phenomena, and disease in particular, span roughly 10 orders of magnitude in length scale. In biology, form drives function. Structural and cell biology explore how a molecule’s structure determines its function, which in turn drives the mechanisms behind cellular processes and, ultimately, human diseases. To understand holistically how a disease develops, it is therefore essential to observe how macromolecules interact within a cell, within an organ, within a human body. Volume electron microscopy (vEM) and cryo-electron microscopy (cryoEM) allow us to probe samples from tissues down to atoms. Correlative light-electron microscopy (CLEM) combines the imaging power of light and electron microscopy, linking molecular activity to cell structure with unmatched precision. By combining light and electron imaging, CLEM offers a clearer view of how cells function, which is crucial for advancing clinical research and diagnostics. The greatest technological challenge is to combine all these imaging modes into a resolution continuum spanning all disease-relevant length and time scales. Our mission is to translate vEM, cryoEM, and CLEM technologies from basic to clinical research and to make them suitable for studying diseases directly in patient samples.

High-resolution imaging for clinical research

We strive to enable clinicians to access unparalleled imaging resolution for investigating complex diseases. CLEM can directly provide detailed structural insights into pathogens, diseased tissues, or abnormal protein formations that are often challenging to study with indirect methods. This could lead to earlier, more accurate diagnoses and better-informed treatment decisions. In addition, electron microscopy data can reveal structural anomalies at the molecular level that may serve as early indicators of disease progression or therapeutic response.

Technology development to foster clinical research

The limitations of hardware and sample preparation across different imaging methods hamper our ability to routinely probe human samples. Part of our effort is devoted to developing new methods that make clinical samples amenable to structural studies