Research

Our research interests lie at the intersection of biophysics and instrument engineering. We develop tools to decipher how biomachines function using state-of-the-art, advanced microscopy to image single molecules at work inside living cells.

localization microscopy

Localization microscopy is used to recover information from the image shape that is formed on the detector. Most commonly, this is used to extract precise spatial information that is obscured by the finite numerical aperture of the imaging system, but can also be used to extract information like z position, emitter color, orientation, and more.

Particle tracking

One key application of localization microscopy is for single-molecule tracking. Here we show the movements of a single protein traversing a micro-scale signaling organelle known as the primary cilium.

"Motional dynamics of single Patched1 molecules in cilia are controlled by Hedgehog and cholesterol," Weiss & Milenkovic, et al. PNAS, (2019). (doi.org/10.1073/pnas.1816747116);

Superresolution

Yet another application of localization microscopy is for super-resolution microscopy. Here, many different molecules are recorded asynchronously by exploiting the photophysical tendency of molecules to convert between fluorescent and non-fluorescent states.

"Cellular inclusion bodies of mutant Huntingtin exon1 obscure small fibrillar aggregate species," Sahl & Weiss, et al. Scientific Reports, (2012). (doi.org/10.1038/srep00895);

High-throughput microscopy

The tradeoff between field-of-view and magnification makes it difficult to image large populations of cells. This poses an especially critical challenge when cells are undergoing dynamic changes that prevent the collection of sufficient statistics. We use flow-based imaging methods to solve that problem and have demonstrated 3D localization microscopy in 1000 cells each minute.

"Three-dimensional localization microscopy in live flowing cells," Weiss et al., Nature Nanotechnology (2020). (doi.org/10.1038/s41565-020-0662-0);