Background

Light microscopy is an extremely powerful tool for investigating biological systems. It is straight forward to use, enables highlighting specific molecules in the sample and putting molecular information into mutual context. Contrary to electron microscopy, it is also applicable to living systems to study their time evolution. However, spatial resolution is limited by diffraction of light waves to about half the wavelength of light or 200 nm, whereas the relevant length scales of the molecular arrangements inside cells are typically much finer. A series of powerful methods have emerged that enable resolution much better than the diffraction limit, reaching into nanometer scales, thus revealing more biologically relevant detail. In our interdisciplinary group at IST Austria (https://danzl-lab.pages.ist.ac.at/), we focus on the development and application of new light microscopy tools with exquisite spatial resolution and on their application in the life sciences. Thus, physicists and biologists/neuroscientists work together to address a particular problem. On the microscopy side, the group has ample experience with stimulated emission depletion (STED) microscopy and expansion microscopy and we apply single-molecule imaging for selected problems. We combine this with state-of-the-art approaches to label and manipulate cells and tissues. We encourage applications for PhD positions both from candidates with a background in physics, engineering, or data science/programming/hardware control as well as biology or neuroscience and related disciplines.

Project I - Super-resolution optical microscopy to decode receptor composition at the single synapse lever in the central nervous system.

Synapses are the highly specialized structures that allow for directed information flux from one neuron to the next and are important sites of signal processing in the brain. Within this project we plan to address receptor composition at synapses directly in brain tissue at unprecedentedly high resolution. This is inherently an interdisciplinary project that spans from the methods development to the specific neuroscience application. The emphasis for the PhD project will be set according to the background of the MolTag student and can focus on the detailed investigation of a particular synaptic system based on the techniques established in the group or, equally importantly, on the optics development to enable higher information content in the measurements. We will collaborate with other MolTag groups such as the Mihovilovic and Maulide groups on e.g. labelling and will profit from the molecular pharmacology expertise in the various MolTag groups.

Project II - Phenotypical alterations in brain disease models

Fluorescence super-resolution imaging enables highlighting specific molecules with high sensitivity and resolution of tens of nanometers, allowing to reconstruct the molecular architecture of synapses and brain tissue. In the framework of this project we intend to investigate the phenotypical and molecular alterations in brain disease models with high information content. For this, we will take advantage both of transcriptomics and high-resolution protein imaging. Here, we will e.g. collaborate with the Novarino group to define the effects and mechanisms of neurodevelopmental disease mutations on a structural and molecular level in the brain. We expect to obtain mechanistic insights into the molecular events leading to neurodevelopmental disease formation.