Connor ScottUniversity of Oxford | OX · Nuffield Department of Clinical Neurosciences
Connor Scott
Doctor of Philosophy
About
24
Publications
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Introduction
Connor Scott is a neuroscientist with over 9 years of human tissue experience, specialising in bringing histology into the modern era by developing workflows to bridge traditional
neuropathology with ‘omics’ technologies using surgical and post-mortem CNS material.
Publications
Publications (24)
Betz cells, named in honor of Volodymyr Betz (1834–1894), who described them as “giant pyramids” in the primary motor cortex of primates and other mammalian species, are layer V extratelencephalic projection (ETP) neurons that directly innervate α‐motoneurons of the brainstem and spinal cord. Despite their large volume and circumferential dendritic...
Neuroanatomical tract tracing methods are fundamental in providing “gold standard” estimates of brain connectivity. However, tracer methods cannot be performed in humans and even in animals, we can only study projections from typically one or two injection sites per animal sacrificed. Orientation-sensitive microscopy techniques such as PLI provide...
The spatial organisation of cellular protein expression profiles within tissue determines cellular function and is key to understanding disease pathology. To define molecular phenotypes in the spatial context of tissue, there is a need for unbiased, quantitative technology capable of mapping proteomes within tissue structures. Here, we present a wo...
Understanding brain structure and function often requires combining data across different modalities and scales to link microscale cellular structures to macroscale features of whole brain organisation. Here we introduce the BigMac dataset, a resource combining in vivo MRI, extensive postmortem MRI and multi-contrast microscopy for multimodal chara...
The acquisition of MRI and histology in the same post-mortem tissue sample enables direct correlation between MRI and histologically-derived parameters. However, there still lacks a standardised automated pipeline to process histology data, with most studies relying on manual intervention. Here, we introduce an automated pipeline to extract a quant...
Understanding brain structure and function often requires combining data across different modalities and scales to link microscale cellular structures to macroscale features of whole brain organisation. Here we introduce the BigMac dataset, a resource combining in vivo MRI, extensive postmortem MRI and multi-contrast microscopy for multimodal chara...
Microscopy data can provide detailed descriptions of how cortical microstructure varies across the brain. However, the relationship between cortical microstructure and MRI signals remains relatively unexplored. Here we develop a pipeline to extract cortical profiles from co-registered MRI and microscopy data in the BigMac dataset. We compare cortic...
Cellular protein expression profiles within tissues are key to understanding disease pathology, and their spatial organisation determines cellular function. To precisely define molecular phenotypes in the spatial context of tissue, there is a need for unbiased, quantitative technology capable of mapping the expression of many hundreds to thousands...
Post-mortem MRI provides the opportunity to acquire high-resolution datasets to investigate neuroanatomy, and validate the origins of image contrast through microscopy comparisons. We introduce the Digital Brain Bank (open.win.ox.ac.uk/DigitalBrainBank), a data release platform providing open access to curated, multimodal post-mortem neuroimaging d...
The acquisition of MRI and histology in the same post-mortem tissue sample enables direct correlation between MRI and histologically-derived parameters. However, there still lacks a standardised automated pipeline to process histology data, with most studies relying on heavy manual intervention. Here, we introduce an automated pipeline to extract q...
Post-mortem MRI provides the opportunity to acquire high-resolution datasets to investigate neuroanatomy, and validate the origins of image contrast through microscopy comparisons. We introduce the Digital Brain Bank (open.win.ox.ac.uk/DigitalBrainBank), an interactive data discovery and release platform providing open access to curated, multimodal...
The BigMac dataset is a unique resource that includes extensive MRI and densely sampled microscopy data acquired in a single, whole macaque brain. However, the high-resolution microscopy currently only informs on the fibre orientations in the 2D plane of sampled slides, precluding 3D reconstruction of the microscopy connectome. Here we use precise...
The pathological hallmark of amyotrophic lateral sclerosis (ALS) is the presence of cytoplasmic inclusions, containing C‐terminal fragments of the protein TDP‐43. Here, we tested the hypothesis that highly sensitive mass spectrometry with parallel reaction monitoring (MS‐PRM) can generate a high‐resolution map of pathological TDP‐43 peptide ratios...
Background
Multimerization is a key process in prion-like disorders such as Alzheimer’s disease (AD), since it is a requirement for self-templating tau and beta-amyloid amyloidogenesis. AT8-immunohistochemistry for hyperphosphorylated tau is currently used for the diagnosis and staging of tau pathology. Given that tau–tau interactions can occur in...
Degeneration of the primary motor cortex is a defining feature of amyotrophic lateral sclerosis (ALS), which is associated with the accumulation of microscopic protein aggregates in neurons and glia. However, little is known about the quantitative burden and pattern of motor cortex proteinopathies across ALS genotypes. We combined quantitative digi...
Diffusion-weighted steady-state free precession (DW-SSFP) is an SNR-efficient diffusion imaging method. The improved SNR and resolution available at ultra-high field has motivated its use at 7T. However, these data tend to have severe B1 inhomogeneity, leading not only to spatially varying SNR, but also to spatially varying diffusivity estimates, c...
Diffusion-weighted steady-state free precession (DW-SSFP) is an SNR-efficient diffusion imaging method. The improved SNR and resolution available at ultra-high field has motivated its use at 7T. However, these data tend to have severe B 1 inhomogeneity, leading not only to spatially varying SNR, but also to spatially varying diffusivity estimates,...
BACKGROUND
The molecular genetic classification of gliomas, particularly identification of isocitrate dehydrogenase (IDH) mutations, is critical for clinical and surgical decision-making. Raman spectroscopy probes the unique molecular vibrations of a sample to accurately characterise its molecular composition. No sample processing is required allow...
Diffusion MRI has the ability to reveal the complex connectivity of the human brain. However, the link between the diffusion signal and the underlying tissue microstructure remains elusive. To drive diffusion MRI validation, we present BigMac: a unique dataset which combines ultra-high angular resolution diffusion MRI with microscopy throughout an...
While nearly comprehensive proteome coverage can be achieved from bulk tissue or cultured cells, the data usually lacks spatial resolution. As a result, tissue based proteomics averages protein abundance across multiple cell types and/or localisations. With proteomics platforms lacking sensitivity and throughput to undertake deep single-cell proteo...
Mutations in the gene encoding the RNA-binding protein TDP-43 cause amyotrophic lateral sclerosis (ALS), clinically and pathologically indistinguishable from the majority of 'sporadic' cases of ALS, establishing altered TDP-43 function and distribution as a primary mechanism of neurodegeneration. Transgenic mouse models in which TDP-43 is overexpre...
Abstract
Objectives To assess the performance of circulating vascular endothelial growth factor (VEGF) levels as a tool for diagnosing giant cell arteritis (GCA) in a cohort of patients referred for assessment of suspected GCA.
Methods We selected 298 patients recruited to the multicentre study Temporal Artery Biopsy versus Ultrasound in diagnosis...
INTRODUCTION: Raman spectroscopy is an emerging biophotonic tool for the identification of disease. By probing the unique molecular vibrations that depend on the composition and structure of samples, it provides a wealth of information on a cellular and molecular level of both solid and liquid specimens without the use of external agents such as dy...
Introduction
Raman spectroscopy is an emerging biophotonic tool for the identification of disease. By probing the unique molecular vibrations that depend on the composition and structure of samples, it provides a wealth of information on a cellular and molecular level of both solid and liquid specimens without the use of external agents such as dye...
Questions
Question (1)
Hey all,
I've tried looking for a solution online but I can't seem to find an answer.
I have isolated cDNA from a cell type of interest and I want to work out if gene X is higher than gene Y within these samples. I have the ct values for all my genes and I also have the primer efficiencies for all the primer pairs used - they vary slightly so I would like to use the Pfaffl method.
The issue I am having is that unlike traditional experiments I don't have a control/treatment group as I'm only interested in this one cell type without any experimental conditions. Would it be wise to normalise gene X and gene Y to a housekeeping gene and compare them relatively (or is this not needed since it's one cell type and I imagine that most if not all genes will be uniform within them), or with this is mind can I just take the ratio between X and Y?
I understand that absolute quantification with recombinant mRNA would provide the answer but I rather not go down that route.
Many thanks for your advice!
