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Biology subjects

Doerner, A.

Publications and source records attributed to Doerner, A..

2 recordsLinked to original sources

OPTIMIZED NEURON TRACING USING POST HOC REANALYSIS

Over the last decade, the advances in Brainbow labeling allowed labeling hundreds of neurons with distinct colors in the same field of view of a brain [1, 2]. Reconstruction (or "tracing") of the 3D structures of these images has been enabled by a growing set of software tools for automatic and manual annotation. It is common, however, to have errors introduced by heuristics used by tracing software, namely that they assume the "best" path is the highest intensity one, a more pertinent issue when dealing with multicolor microscope images. Here, we report nCorrect, an algorithm for correcting this error by reanalyzing previously created neuron traces to produce more physiologically-relevant ones. Specifically, we use a four dimensional minimization algorithm to identify a more-optimal reconstruction of the image, allowing us to better take advantage of existing manual tracing results. We define a new metric (hyperspectral cosine similarity) for describing the similarity of different neuron colors to each other. Our code is available in an open source license and forms the basis for future improved neuron tracing software.

neuroscience↗

Coiled coil control of diverse EGFR functions

EGFR exhibits biased signaling, whereby growth factor or mutation-dependent changes in receptor conformation and/or dynamics elicit distinct intracellular outcomes. We report that many outcomes associated with activated EGFR are controlled by a two-state coiled coil switch located within the juxtamembrane segment (JM), an essential component of the cytosolic dimer interface. The position of this switch defines the path of endocytic trafficking and whether or not EGFR is degraded within lysosomes. JM coiled coil identity also predicts kinase-independent effects of oncogenic EGFR mutations and clinically relevant tyrosine kinase inhibitors (TKIs) that promote efficient, lysosome-based EGFR degradation. These findings provide a model for biased EGFR signaling, insights into kinase-independent activities of EGFR and clinically relevant TKIs, and identify new strategies for modulating protein lifetime.

biochemistry↗