We specialize in the design, construction and implementation of bespoke single molecule fluorescence microscopy instrumentation to interrogate the structure and dynamics of biomolecules.
We image single molecules, one at a time, to gain transformative new insights into biological function on the nanoscale. Unlike many scientific tools that report an average value, single-molecule imaging allows us to reveal otherwise hidden information, such as transient intermediate states and dynamic fluctuations.
We employ cutting edge methods such as stepwise photobleaching, alternating laser excitation (ALEX) and single molecule Förster resonance energy transfer (smFRET) to unveil important nanoscopic mechanisms that govern important biological interactions, including those involved in Alzheimer's Disease.
Our research group specializes in cuting-edge biophotonic sensing technologies to detect blood-based biomarkers of dementia, including Alzheimer's disease. By leveraging guided mode resonance (GMR) biosensors, we aim to achieve highly sensitive and accurate biomarker detection.
Our approaches integrate advanced photonic tools with multiplexing capabilities to enable parallel readouse of protein and exosome biomarkers from a small droplet of sample.
Through this work, we aim to advance diagnostic technologies and pave the way for earlier detection of neurodegenartive diseases.
Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of toxic protein fragments in the brain. We aim to understand how these fragments grow and develop, how they manipulate and rupture cellular membranes and how to stop them.
One analogy to the theory behind the search for an effective drug is a flooded apartment caused by a burst pipe. Drug discovery has focused on duct taping the pipe, but without understanding and preventing the root cause.
We combine major developments in biochemistry and single-molecule imaging to provide real-time spectroscopic fingerprints of Alzheimer's disease on the nanoscale, providing the scientific community with a new suite of biophysical tools from which to more effectively and efficiently screen the next generation of therapeutics.
Biologic membranes are extremely complex and crowded environments. This complexity has motivated us to develop a variety of simpler model membrane systems, including vesicles, nanodiscs and supported bilayers whose size, architecture, phase and composition can be controlled with exquisite precision.
We use these model membranes in combination with smFRET to unveil the multi-step mechanisms of membrane disruption and fusion induced by a wide variety of proteins and disruptive molecules.
We measure the fluorescence spectra, anisotropy and lifetime of fluorescent molecules in solution. The lifetime in particular is typically influenced by the molecule's local environment and additional processes such as energy transfer, molecular rotation and collisions.
We measure the lifetime using the combination of picosecond pulsed lasers, advanced time-tagging electronics, FLIM microscopy, and single-photon detection to access information about the local chemical environment of molecules, kinetic rates, and mechanisms that take place on the pico-to-nano second.
We probe the conformational dynamics of molecular machinery operating on DNA using advanced single-molecule spectroscopy tools. In particular, we study helicase motors which are essential in DNA metabolism. It has generally been assumed that proteins are displaced from DNA by helicases, however, the actual method of protein translocation in response to protein roadblocks remains to be fully elucidated.