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Graham Knott

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Related publications (97)

Page 4 of 5

Lamellar Schwann Cells in the Pacinian Corpuscle Potentiate Vibration Perception

Graham Knott, Mary-Claude Croisier-Coeytaux, Stéphanie Clerc, Jérôme Blanc

Pacinian corpuscles are among the most sensitive mechanoreceptors found in vertebrates, and they are tuned to vibrations in the highest perceptible frequency range (100 to 2000 Hz). One of their anatomical hallmarks is the onion-like cell layers surroundin ...

AMER ASSOC ADVANCEMENT SCIENCE2025

Gas cluster ion beam SEM for imaging of large tissue samples with 10 nm isotropic resolution

Graham Knott

We demonstrate gas cluster ion beam scanning electron microscopy (SEM), in which wide-area ion milling is performed on a series of thick tissue sections. This three-dimensional electron microscopy technique acquires datasets with

Nature Publishing Group2020

Imaging green fluorescent protein-labeled neurons using light and electron microscopy

Graham Knott

The ability to observe axons and dendrites with transmission electron microscopy (EM) after they have been previously imaged live with laser-scanning microscopy is a useful technique to study their synaptic connectivity. This protocol provides a detailed m ...

2013

Computer assisted detection of axonal bouton structural plasticity in in vivo time-lapse images

Graham Knott, Anne Alison Jorstad

The ability to measure minute structural changes in neural circuits is essential for long-term in vivo imaging studies. Here, we propose a methodology for detection and measurement of structural changes in axonal boutons imaged with time-lapse two-photon l ...

Elife Sciences Publications Ltd2017

Retromer deficiency in Tauopathy models enhances the truncation and toxicity of Tau

Graham Knott, Evelyne Ruchti, Catherine Maclachlan, Greta Limoni, Brian Donal McCabe, Wei Jiao

Alteration of the levels, localization or post-translational processing of the microtubule associated protein Tau is associated with many neurodegenerative disorders. Here we develop adult-onset models for human Tau (hTau) toxicity in Drosophila that enabl ...

Nature Portfolio2022

Efficient scanning for em based target localization

Pascal Fua, Graham Knott, Raphael Sznitman, Aurélien Lucchi

We presented an approach for speeding-up image acquisition when tasked with localizing specific structures in FIB-SEM imagery. It exploits the fact that low-quality images can be acquired faster than higher-quality ones and yet be sufficient for inference ...

2014

In-vivo single neuron axotomy triggers axon regeneration to restore synaptic density in specific cortical circuits

Graham Knott, Bohumil Maco

To what extent, how and when axons respond to injury in the highly interconnected grey matter is poorly understood. Here we use two-photon imaging and focused ion beam-scanning electron microscopy to explore, at synaptic resolution, the regrowth capacity o ...

Nature Research2013

Amygdala GluN2B-NMDAR dysfunction is critical in abnormal aggression of neurodevelopmental origin induced by St8sia2 deficiency

Graham Knott, Maria del Carmen Sandi Perez, Olivia Zanoletti, Jocelin Grosse, Elias Georges Gebara, Wei Tang, Alexandre Claude Gustave Bacq, Johannes Gräff, Catherine Maclachlan, Jose Vicente Sanchez Mut, Bianca Ambrogina Silva, Simone Astori

Aggression is frequently observed in neurodevelopmental psychiatric disorders such as schizophrenia, autism, and bipolar disorder. Due to a lack of understanding of its underlying mechanisms, effective treatments for abnormal aggression are still missing. ...

2020

Learning Context Cues for Synapse Segmentation in EM Volumes

Pascal Fua, Graham Knott, Karim Ali, Carlos Joaquin Becker

We present a new approach for the automated segmentation of excitatory synapses in image stacks acquired by electron microscopy. We rely on a large set of image features specifically designed to take spatial context into account and train a classifier that ...

2012

Efficient Scanning for EM Based Target Localization

Pascal Fua, Graham Knott, Raphael Sznitman, Aurélien Lucchi, Natasa Pjescic-Emedi

For biologists studying the morphology of cells, Electron Microscopy (EM) is the method of choice with its {\it nm} resolution, across increasingly larger volumes. However, the time necessary to acquire such image series is long and often limits the amount ...

2012

Conditional expression of Parkinson's disease-related R1441C LRRK2 in midbrain dopaminergic neurons of mice causes nuclear abnormalities without neurodegeneration

Liliane Glauser, Graham Knott, Elpida Tsika, Shi-Yan Caroline Foo

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant Parkinson's disease (PD). The clinical and neurochemical features of LRRK2-linked PD are similar to idiopathic disease although neuropathology is somewhat heter ...

Elsevier2014

Dynamics of CLIMP-63 S-acylation control ER morphology

Kathryn Hess Bellwald, Béatrice Kunz, Graham Knott, Françoise Gisou van der Goot Grunberg, Laurence Gouzi Abrami, Vassily Hatzimanikatis, Patrick Alain Sandoz, Robin Alexander Denhardt-Eriksson, Sylvia Ho, Luciano Andres Abriata, Catherine Maclachlan, Gard Spreemann

A key player in the formation of endoplasmic reticulum sheets is CLIMP-63, but mechanistic details remained elusive. Here authors combined cellular experiments and mathematical modelling to show that S-acylation of CLIMP-63 regulates its function by mediat ...

Nature Portfolio2023

In vivo modeling of human neuron dynamics and Down syndrome

Graham Knott

Harnessing the potential of human stem cells for modeling the physiology and diseases of cortical circuitry requires monitoring cellular dynamics in vivo. We show that human induced pluripotent stem cell (iPSC)-derived cortical neurons transplanted into th ...

American Association for the Advancement of Science2018

Ultrastructural basis of strong unitary inhibition in a binaural neuron

Graham Knott, Ralf Schneggenburger, Enida Gjoni, Clémentine Léa Aguet, Daniela Andrea Sahlender

Binaural neurons in the lateral superior olive (LSO) integrate sound information arriving from each ear, and powerful glycinergic inhibition of these neurons plays an important role in this process. In the present study, we investigated the ultrastructural ...

WILEY2018

Universal sample holder

Graham Knott

This device is for holding samples during their preparation prior to imaging in the electron microscope. The design means it can be transferred between the light and electron microscopes as well as trimming devices used to prepare the final sample. It can ...

2013

Imaging liver and brain glycogen metabolism at the nanometer scale

Arnaud Comment, Graham Knott, Yuhei Takado, Anders Meibom, Stéphane Laurent Escrig

In mammals, glycogen synthesis and degradation are dynamic processes regulating blood and cerebral glucose-levels within a well-defined physiological range. Despite the essential role of glycogen in hepatic and cerebral metabolism, its spatiotemporal distr ...

Elsevier Science Bv2015

Maturation of Complex Synaptic Connections of Layer 5 Cortical Axons in the Posterior Thalamic Nucleus Requires SNAP25

Graham Knott, Catherine Maclachlan

Synapses are able to form in the absence of neuronal activity, but how is their subsequent maturation affected in the absence of regulated vesicular release? We explored this question using 3D electron microscopy and immunoelectron microscopy analyses in t ...

OXFORD UNIV PRESS INC2021

Nuclear and cytoplasmic huntingtin inclusions exhibit distinct biochemical composition, interactome and ultrastructural properties

Graham Knott, Hilal Lashuel, Mary-Claude Croisier-Coeytaux, Anne-Laure Mahul Mellier, Niran Maharjan, Johannes Burtscher, Nathan Alain Denis Riguet, Joanna Kathleen Hastings

Despite the strong evidence linking the aggregation of the Huntingtin protein (Htt) to the pathogenesis of Huntington’s disease (HD), the mechanisms underlying Htt aggregation and neurodegeneration remain poorly understood. Herein, we investigated the ultr ...

Springer Nature2021

Identification of aminopyrimidine-sulfonamides as potent modulators of Wag31-mediated cell elongation in mycobacteria

Kai Johnsson, Gaëlle Séraphine Kolly, Graham Knott, John McKinney, Stewart Cole, Neeraj Dhar, Monica Rengifo Gonzalez, Ruben Hartkoorn, Isabella Santi, Edina Rita Székely, François Signorino-Gelo, Jan Lars Rybniker, Anthony Vocat

There is an urgent need to discover new antitubercular agents with novel mechanisms of action in order to tackle the scourge of drug-resistant tuberculosis. Here, we report the identification of such a molecule - an AminoPYrimidine-Sulfonamide (APYS1) that ...

Wiley-Blackwell2017

Toward Biophysical Mechanisms of Neocortical Computation after 50 Years of Barrel Cortex Research

Carl Petersen, Graham Knott, Felix Schürmann

2021