Development of advanced optical tools for studying cellular mechanics at high spatial and temporal resolution
A long-standing aim in the life sciences is to understand development and morphogenesis, i.e. how organismal shape is encoded by the genome and how cellular mechanics are involved in its execution. Lately, investigations have started to focus on the mechanical properties of the involved multicellular compartments, and the interwoven mechanical - molecular interactions at the cellular scale. While molecular components can routinely be visualized with fluorescence microscopy, assessing the mechanical properties of living cells with similar spatio-temporal resolution in a non-invasive fashion has long been an open challenge.

Recently, a new type of optical elastography, namely Brillouin microscopy (BM), has emerged as a non-destructive, label- and contact-free technique which can probe visco-elastic properties of materials with diffraction-limited resolution in 3D. Yet, despite ongoing improvements, virtually all current implementations suffer from very low speed, high phototoxicity, and difficulties in quantification, thus prohibiting meaningful investigations in the life sciences.

In this interdisciplinary proposal, my group will develop unique and innovative optical imaging technologies based on BM to overcome its current drawbacks and to establish it as a revolutionary tool for live tissue and cellular biophysics studies. In particular, we will work towards a highly-multiplexed BM with selective-plane illumination to maximize speed, resolution and depth penetration, while minimizing photodamage (Aim 1). At the same time, we will combine BM with other imaging modalities that will allow us to obtain correlative datasets and to accurately quantify the measured mechanical properties (Aim 2). We will then apply these methodological advancements together with fellow biologists to study the role of elasticity in tissue morphogenesis and self-organisation, thereby contributing to a better understanding of the role of biomechanics in developmental biology (Aim 3).