See deeper with adaptive six-dimensional nanoscopy


June 08, 2023

(Nanowerk News) Matthew Lew, a professor of electrical and systems engineering at the McKelvey School of Engineering at Washington University in St. Louis, has received a five-year $2 million Maximization Research Investigator Award (MIRA) from the National Institutes of Health (NIH ) to support his ongoing work to improve microscopic imaging techniques. Lew will use the technology to better visualize individual molecules, especially those involved in Alzheimer’s disease.

Lew’s previous research paired chemical and optical approaches to take a closer look at what individual molecules are doing using a five-dimensional optical microscope. Now, he will move into another dimension and combine model-driven design algorithms with data-driven deep learning methods to produce intelligent microscopes.

“We pushed nanoscopy, also called super-resolution optical microscopy, into six dimensions to measure the 3D position and 3D orientation of individual molecules in biological systems,” said Lew. “When we started this project six years ago, we weren’t sure how feasible it would be, but we recently published the first demonstration of 6D imaging in cells (Nature Photonics, “Six-dimensional imaging of a single molecule with isotropic resolution using a multi-view reflector microscope”). We are exploring how to make the technology more precise, more sensitive, faster and easier to use.”

The main goal of this project is to enable measurements that are not possible with today’s advanced nanoscopes. By developing smart microscopes that can adapt as they collect more data, Lew and his team aim to discover how dynamic interactions between individual biomolecules at the nanoscale influence their collective function and organization in complex biophysical processes, such as the evolution of biomolecular condensates and the diseases they cause. by their dysregulation, including Alzheimer’s and Huntington’s disease.

“I am excited to partner with collaborators at McKelvey Engineering to use 6D nanoscopy to study biomolecules in a way no other technology can,” said Lew.

Lew’s collaborators include Jai Rudra, a professor of biomedical engineering, and Rohit Pappu, Gene K. Beare Honorary Professor and director of the Center for Biomolecular Condensates, both at McKelvey Engineering. With this multidisciplinary expertise, the team sought to understand variations in self-assembled peptide architectures for biomaterial applications and visualize dynamic network architectures in condensates.

“One of the best aspects of the NIH MIRA program is the flexibility for investigators to follow important new research directions as opportunities arise,” said Lew. “We will be exploring many possibilities, including ones that go beyond what we can currently imagine.”


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