Six Ambitious Interdisciplinary Projects in Imaging to Start in 2022

Towards more accurate large-scale gene expression profiles

Laboratory of Neurodevelopmental Systems Biology (Dr. Gioele La Manno) and Bioimage Analysis and Computational Microscopy (Dr. Martin Weigert)

Spatial transcriptomics – a nascent field arising from the combination of cutting-edge microscopy with gene-specific in-situ labeling – can be used to generate large gene expression profiles of messenger RNA. This gives scientists an indication of the relative expression rates of different genes in the same environment. EPFL scientists at these two labs are profiling the expression of up to two hundred genes simultaneously in the developing brain using Hybridization In Situ Sequencing (HybISS). This cutting-edge method relies on computational processing methods that are still immature, can be hard to use and error-prone. In this project, Dr. La Manno and Dr. Weigert will develop a computational spatial transcriptomics framework – called Codebook-Aware ILP Detection and Tracking (CBAIDT) – that leverages modern computer vision techniques while using a novel tracking approach to substantially increase the accuracy and robustness of gene expression map generation.

Fast multifunctional microscopy for photoelectrochemistry and bioimaging

Laboratory of Nanoscience for Energy Technologies (Prof. Giulia Tagliabue) and Laboratory for Bio- and Nano-Instrumentation (Prof. Georg Fantner)

Scanning probe methods – and in particular, the combination of scanning ion conductance microscopy (SICM) and scanning electrochemical microscopy (SECM) – have emerged as unique tools for studying materials and mechanisms in complex, multistep chemical reactions such as CO₂ reduction. However, they are notoriously slow in image acquisition, making them ill-suited for studying the dynamics of energy conversion processes. In this project, these two EPFL labs will develop advanced hardware and software components for a unique, fast SICM-SECM imaging method that can be easily deployed within the EPFL community, and beyond. Their method has great potential for the design of energy devices, as well as emerging cross-disciplinary applications such as the nanoelectrochemistry of single-cell signaling.

A more effective 3D-imaging system for Earth System Science and Navigation

Laboratory for Visual Intelligence for Transportation, or VITA (Prof. Alexandre Alahi) and Extreme Environments Research Laboratory, or EERL (Prof. Julia Schmale)

3D image reconstruction or depth estimation is at the core of applications in navigation as well as Earth system science. Significant advances have been made in the field of computer vision to obtain 3D information from various types of cameras. Yet, these techniques still face limitations for a number of applications. In this project, the VITA (Prof. Alahi ) and EERL (Prof. Schmale) groups will pool their complementary skills to develop new machine-learning-based methods that can estimate depth from a large number of camera configurations, including from a novel 360° camera application. With their work, the teams will spearhead developments in the domain of 3D wave reconstruction and sea-ice classification, as well as autonomous navigation on water. iThe learning framework will be available as an open-source library that caters to the needs of many imaging applications.

3D nanoscopic Imaging of genome ultrastructure in cells

Laboratory of Systems Biology and Genetics (Prof. Bart Deplancke) and Laboratory of Biophysical Chemistry of Biomolecules (Prof. Beat Fierz)

Each human cell contains around two meters of DNA tightly packaged in its nucleus. An exquisite organization is critical to ensure that the DNA can be accessed by the many important genetic processes. This organization is achieved by wrapping the DNA around millions of tiny protein spindles, forming a complex called chromatin. Chromatin governs many key cellular functions and, when malfunctions in its organization can lead to serious diseases. As of now, there exist no imaging methods that allows scientists to observe chromatin organization directly in the nucleus without seriously interfering with its local structure. In this project, two EPFL labs from different schools will develop novel methods for imaging the ultrastructure of chromatin on the level of individual genes and their regulatory regions in cells using in situ fluorescent chemical labeling, 3D nanoscopy and sequencing-based methods.

High-speed multimodal super-resolution microscopy

Advanced Quantum Architecture Lab (Prof. Edoardo Charbon) and Laboratory of Nanoscale Biology (Prof. Aleksandra Radenovic)

In this project, scientists from two EPFL labs will combine their know-how to develop a new high-speed microscopy system that can reveal single-molecule dynamics with unprecedented detail, including in liquids. The system will also allow scientists to assess how individual molecules behave, interact and self-organize at the solid-liquid interface. More specifically, they will enhance the system’s high-speed temporal acquisition capability by incorporating the single-photon avalanche diode (SPAD) arrays developed in Prof. Charbon’s lab into the state-of-the-art widefield super-resolution microscope developed in Prof. Radenovic’s lab.

Connecting imaging to mechanical measurements

Laboratory of Engineering Mechanics of Soft Interfaces (Prof. John Kolinski) and the holder of the Gabriella and Giorgi Cavaglieri Chair in Life Sciences (Prof. Alexandre Persat)

When it comes to characterizing mechanics at the cellular scale, the accuracy and precision of current methods are still limited. In this project, Prof. Kolinski and Prof. Persat will connect imaging to mechanical measurements by developing a set of hardware and software tools that can measure microscale 3D force fields and surface stresses. The goal will be to improve our understanding of the function of forces in the physiology of biological systems. The new tools can then be used to study the mechanobiology of bacterial pathogens and will be widely applicable in other fields as well, such as microscale mechanics and the study of soft matter.