Graham William Knott

A bioengineered human urothelial organoid model reveals the urine-urothelium interplay in tissue resilience and UPEC recurrence in urinary tract infections

The paper develops a human urothelial organoid model to study urine-urothelium interactions in UTI resilience and UPEC recurrence, finding that high-solute urine weakens tissue and promotes CWD UPEC formation.

Recapitulating Parkinson's pathology in human iPSC dopaminergic neurons reveals new mechanistic insights into Lewy body formation and heterogeneity.

This study uses human iPSC-derived dopaminergic neurons to model Parkinson's Lewy body pathology without genetic modification, revealing mechanisms of aSyn aggregation and morphological diversity.

Lamellar Schwann cells in the Pacinian corpuscle potentiate vibration perception

This study identifies lamellar Schwann cells in Pacinian corpuscles as key elements that potentiate mechanosensitivity through structural and functional interactions with afferent axons.

Mechanisms of axoneme and centriole elimination in Naegleria gruberi

This study identifies mechanisms by which Naegleria gruberi eliminates axonemes and centrioles during life cycle reversion, revealing lysosomal and proteasome-dependent pathways and extracellular shedding.

Dissecting the differential role of C-terminal truncations in the regulation of aSyn pathology formation and the biogenesis of Lewy bodies

This study investigates how C-terminal truncations of alpha-synuclein (aSyn) affect Lewy body (LB) formation and pathology in Parkinson's disease by analyzing their role in fibril processing and aggregation.

Membrane mechanics dictate axonal morphology and function

This study shows that axon morphology and function are influenced by membrane mechanics, with activity modulating cholesterol levels and affecting conduction velocity.

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

The paper examines the biochemical composition, interactome, and ultrastructural properties of nuclear and cytoplasmic Htt inclusions in mammalian cells and neurons.

Maturation of complex synaptic connections of layer 5 cortical axons in the posterior thalamic nucleus requires SNAP25

This study shows that SNAP25 is required for the maturation of complex synaptic connections in layer 5 cortical axons in the posterior thalamic nucleus, but not for their initial formation.

Ultrastructural comparison of dendritic spine morphology preserved with cryo and chemical fixation

The paper compares dendritic spine morphology preserved with cryo and chemical fixation, finding cryo fixation results in thinner spine necks and independent neck-head geometry.

The process of Lewy body formation, rather than simply alpha-synuclein fibrillization, is the major driver of neurodegeneration in synucleinopathies

This study develops a neuronal model of Lewy body formation and shows that the process of Lewy body maturation, not just fibrillization, drives neurodegeneration in synucleinopathies.

GCIB-SEM: A path to 10 nm isotropic imaging of cubic millimeter volumes

The paper introduces GCIB-SEM, a 3D electron microscopy technique that provides <10 nm isotropic resolution for large volumes, improving z-resolution and compatibility with multibeam SEMs.

The making of a Lewy body: the role of alpha-synuclein post-fibrillization modifications in regulating the formation and the maturation of pathological inclusions.

Calpain-1/2 cleavage of the alpha-synuclein C-terminus after fibril formation is reported to drive seeding, aggregation and the maturation of Lewy-body-like inclusions in primary neurons.

The architecture of the endoplasmic reticulum is regulated by the reversible lipid modification of the shaping protein CLIMP-63

This paper shows that ZDHHC6-mediated S-palmitoylation of CLIMP-63 regulates ER morphology by controlling its localization and abundance in mammalian cells.

Locally coordinated synaptic plasticity shapes cell-wide plasticity of visual cortex neurons in vivo

The paper shows that local synaptic plasticity, mediated by Arc, coordinates potentiation and depression of adjacent spines to shape functional neuronal responses in vivo.