Timothy Elston

Deep learning enables structured illumination microscopy with low light levels and enhanced speed

Nature Communications · 2020 · 257 citations

Structured illumination microscopy (SIM) surpasses the optical diffraction limit and offers a two-fold enhancement in resolution over diffraction limited microscopy. However, it requires both intense illumination and multiple acquisitions to produce a single high-resolution image. Using deep learning to augment SIM, we obtain a five-fold reduction in the number of raw images required for super-resolution SIM, and generate images under extreme low light conditions (at least 100× fewer photons). W…

Biosensors based on peptide exposure show single molecule conformations in live cells

Cell · 2021 · 36 citations

Recurrent mismatch binding by MutS mobile clamps on DNA localizes repair complexes nearby

Proceedings of the National Academy of Sciences · 2020 · 29 citations

DNA mismatch repair (MMR), the guardian of the genome, commences when MutS identifies a mismatch and recruits MutL to nick the error-containing strand, allowing excision and DNA resynthesis. Dominant MMR models posit that after mismatch recognition, ATP converts MutS to a hydrolysis-independent, diffusive mobile clamp that no longer recognizes the mismatch. Little is known about the postrecognition MutS mobile clamp and its interactions with MutL. Two disparate frameworks have been proposed: One…

Mechanistic models of PLC/PKC signaling implicate phosphatidic acid as a key amplifier of chemotactic gradient sensing

PLoS Computational Biology · 2020 · 8 citations

Chemotaxis of fibroblasts and other mesenchymal cells is critical for embryonic development and wound healing. Fibroblast chemotaxis directed by a gradient of platelet-derived growth factor (PDGF) requires signaling through the phospholipase C (PLC)/protein kinase C (PKC) pathway. Diacylglycerol (DAG), the lipid product of PLC that activates conventional PKCs, is focally enriched at the up-gradient leading edge of fibroblasts responding to a shallow gradient of PDGF, signifying polarization. To…

Particle-based simulations reveal two positive feedback loops allow relocation and stabilization of the polarity site during yeast mating

PLoS Computational Biology · 2023-10-02 · 7 citations

Many cells adjust the direction of polarized growth or migration in response to external directional cues. The yeast Saccharomyces cerevisiae orient their cell fronts (also called polarity sites) up pheromone gradients in the course of mating. However, the initial polarity site is often not oriented towards the eventual mating partner, and cells relocate the polarity site in an indecisive manner before developing a stable orientation. During this reorientation phase, the polarity site displays e…