Caron Jacobs

University of Cape Town

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Pedro M. Pereira

Universidade Nova de Lisboa

Ricardo Henriques

MRC Laboratory for Molecular Cell Biology

Jason Mercer

University of Birmingham

David Albrecht

Max Planck Institute for the Science of Light

Teng‐Leong Chew

Howard Hughes Medical Institute

Adán Guerrero

Universidad Nacional Autónoma de México

Claire M. Brown

McGill University

Philip E. Hockberger

Northwestern University

Michelle S. Itano

University of North Carolina at Chapel Hill

Kildare Miranda

Universidade Federal do Rio de Janeiro

Cooperative Institutions

Universidad Nacional Autónoma de México

University of Cape Town

European Molecular Biology Organization

University College London

MRC Laboratory for Molecular Cell Biology

Centre National de la Recherche Scientifique

Howard Hughes Medical Institute

University of Wisconsin–Madison

Medical Research Council

Consejo Nacional de Investigaciones Científicas y Técnicas

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Quantitative mapping and minimization of super-resolution optical imaging artifacts

Nature Methods (2018)

S J Culley David Albrecht Caron Jacobs Pedro M. Pereira Christophe Leterrier

10.1038/nmeth.4605

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Citations (329)

Journal of the South African Veterinary Association (2014)

H Aitchison Petrus Poolman Marilette Coetzer Caron Griffiths Caron Jacobs

Infections in broilers and broiler breeders by Enterococcus cecorum, causing clinical disease, have increasingly been described in various countries in the Northern Hemisphere over the past decade. This case report describes an outbreak of enterococcal-associated vertebral osteoarthritis (EVOA) in male broiler breeders in several flocks in South Africa. Male birds aged 4 and 9 weeks displayed the common presentation of lameness, paresis or complete paralysis. Autopsies of culled birds revealed masses on caudal thoracic vertebrae T5-T7, with vertebral osteomyelitis and spondylitis. Microbiological assays identified E. cecorum cultured from spondylitic lesions. Affected flocks were treated with amoxycillin at 25 mg/kg in the drinking water for 5 days, resulting in decreased numbers of lame birds and culls. The origin and pathogenesis of EVOA are poorly understood, which limits prevention to environmental factors that may inhibit systemic access by the enteric bacteria. Skeletal growth trends of male birds are thought to increase their susceptibility to bacterial colonisation at sites of skeletal strain, resulting in abscesses and lesions. Evidence points to the emergence of E. cecorum strains with increased pathogenicity; this highlights the need for greater understanding of the origins, treatment and prevention of EVOA to minimise its economic impact on poultry operations.

Flock

10.4102/jsava.v85i1.1077

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Citations (28)

Author Correction: Quantitative mapping and minimization of super-resolution optical imaging artifacts

Nature Methods (2020)

S J Culley David Albrecht Caron Jacobs Pedro M. Pereira Christophe Leterrier

Minification

10.1038/s41592-020-00983-7

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Citations (1)

The nanoscale organisation of HIV cell surface receptors CD4 and CCR5

Doctoral thesis, UCL (University College London). (2018)

Caron Jacobs

The plasma membrane serves as the cell’s front line for interactions with, and response to, the external environment. The molecular mechanisms and regulation of cellular responses to extracellular signals are determined by the spatial organisation and dynamics of the various components comprising the plasma membrane. CD4 and CCR5 are two key cell surface molecules with important roles in immune cell function and regulation. They are also co-opted as the primary receptor and a co-receptor, respectively, by HIV. Biochemical studies have provided a detailed understanding of the molecular mechanisms of these interactions. Until recently, however, the small scale and rapid dynamics of these interactions has meant that a detailed view of the topology of the cell membrane and the organisation of receptors first encountered by the virus has been beyond the resolving power of available tools. The increasing capabilities of the emerging and rapidly developing super-resolution microscopy technologies are now optimally poised for us to address some of these questions. In this work, I have applied single molecule localization microscopy to unveil some of the nanoscale organisational properties of the cell surface receptors CD4 and CCR5. I have worked on the development of small labelling probes for CD4 and addressed some of the key aspects of sample preparation and labelling that can artificially alter the distribution of membrane associated target molecules. Here I report the first quantitative characterisation of the nanoscale organisation of CD4 and CCR5 in lymphoid cell plasma membranes, as well as how this organisation changes under different conditions, such as in response to cell signal-mimicking stimulation, or exposure to HIV envelope. This approach to characterising membrane receptor organisation can be further applied to in-depth studies of early host cell-virus interactions, as well as to other cell surface receptors and their organisation in the context of key cellular functions.

Cell membrane

Cell surface receptor

Cell Signaling

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Investigating Hepatitis C Virus Infection Using Super-Resolution Microscopy

Methods in molecular biology (2018)

Pedro M. Pereira Caron Jacobs Joe Grove

Immunostaining

10.1007/978-1-4939-8976-8_17

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Citations (3)

Fix Your Membrane Receptor Imaging: Actin Cytoskeleton and CD4 Membrane Organization Disruption by Chemical Fixation

Frontiers in Immunology (2019)

Pedro M. Pereira David Albrecht S J Culley Caron Jacobs Mark Marsh

Single-molecule localization microscopy (SMLM) techniques allow near molecular scale resolution ($\sim$ 20nm) as well as precise and robust analysis of protein organization at different scales. SMLM hardware, analytics and probes have been the focus of a variety of studies and are now commonly used in laboratories across the world. Protocol reliability and artefact identification are increasingly seen as important aspects of super-resolution microscopy. The reliability of these approaches thus requires in-depth evaluation so that biological findings are based on solid foundations. Here we explore how different fixation approaches that disrupt or preserve the actin cytoskeleton affect membrane protein organization. Using CD4 as a model, we show that fixation-mediated disruption of the actin cytoskeleton correlates with changes in CD4 membrane organization. We highlight how these artefacts are easy to overlook and how careful sample preparation is essential for extracting meaningful results from super-resolution microscopy.

10.3389/fimmu.2019.00675

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Citations (54)

Pinpointing Cell Identity in Time and Space

Frontiers in Molecular Biosciences (2020)

Anca F. Savulescu Caron Jacobs Yutaka Negishi Laurianne Davignon Musa M. Mhlanga

Mammalian cells display a broad spectrum of phenotypes, morphologies, and functional niches within biological systems. Our understanding of mechanisms at the individual cellular level, and how cells function in concert to form tissues, organs and systems, has been greatly facilitated by centuries' of extensive work to classify and characterize cell types. Classic histological approaches are now complemented with advanced single-cell sequencing and spatial transcriptomics for cell identity studies. Emerging data suggests that additional levels of information should be considered, including the subcellular spatial distribution of molecules such as RNA and protein, when classifying cells. In this Perspective piece we describe the importance of integrating cell transcriptional state with tissue and subcellular spatial and temporal information for thorough characterisation of cell type and state. We refer to recent studies making use of single cell RNA-seq and/or image-based cell characterisation, which highlight a need for such in-depth characterisation of cell populations. We also describe the advances required in experimental, imaging and analytical methods to address these questions. This Perspective concludes by framing this argument in the context of projects such as the Human Cell Atlas, and related fields of cancer research and developmental biology.

Cell type

10.3389/fmolb.2020.00209

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Citations (19)

Single-molecule super-resolution imaging of T-cell plasma membrane CD4 redistribution upon HIV-1 binding

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Yue Yuan Caron Jacobs Isabel Llorente‐Garcia Pedro M. Pereira Scott P. Lawrence

The first step of cellular entry for the human immunodeficiency virus type-1 (HIV-1) occurs through the binding of its envelope protein (Env) with the plasma membrane receptor CD4 and co-receptor CCR5 or CXCR4 on susceptible cells, primarily CD4 + T cells and macrophages. Although there is considerable knowledge of the molecular interactions between Env and host cell receptors that lead to successful fusion, the precise way in which HIV-1 receptors redistribute to sites of virus binding at the nanoscale remains unknown. Here, we quantitatively examine changes in the nanoscale organisation of CD4 on the surface of CD4 + T cells following HIV-1 binding. Using single-molecule super-resolution imaging, we show that CD4 molecules are distributed mostly as either individual molecules or small clusters of up to 4 molecules. Following virus binding, we observe a local 3-to-10-fold increase in cluster diameter and molecule number for virus-associated CD4 clusters. Moreover, a similar but smaller magnitude reorganisation of CD4 was also observed with recombinant gp120. For the first time, our results quantify the nanoscale CD4 reorganisation triggered by HIV-1 on host cells. Our quantitative approach provides a robust methodology for characterising the nanoscale organisation of plasma membrane receptors in general with the potential to link spatial organisation to function.

Cell membrane

Receptor–ligand kinetics

10.1101/2021.01.05.425371

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Citations (2)

Single-Molecule Super-Resolution Imaging of T-Cell Plasma Membrane CD4 Redistribution upon HIV-1 Binding

Viruses (2021)

Yue Yuan Caron Jacobs Isabel Llorente‐Garcia Pedro M. Pereira Scott P. Lawrence

The first step of cellular entry for the human immunodeficiency virus type-1 (HIV-1) occurs through the binding of its envelope protein (Env) with the plasma membrane receptor CD4 and co-receptor CCR5 or CXCR4 on susceptible cells, primarily CD4+ T cells and macrophages. Although there is considerable knowledge of the molecular interactions between Env and host cell receptors that lead to successful fusion, the precise way in which HIV-1 receptors redistribute to sites of virus binding at the nanoscale remains unknown. Here, we quantitatively examine changes in the nanoscale organisation of CD4 on the surface of CD4+ T cells following HIV-1 binding. Using single-molecule super-resolution imaging, we show that CD4 molecules are distributed mostly as either individual molecules or small clusters of up to 4 molecules. Following virus binding, we observe a local 3-to-10-fold increase in cluster diameter and molecule number for virus-associated CD4 clusters. Moreover, a similar but smaller magnitude reorganisation of CD4 was also observed with recombinant gp120. For one of the first times, our results quantify the nanoscale CD4 reorganisation triggered by HIV-1 on host CD4+ T cells. Our quantitative approach provides a robust methodology for characterising the nanoscale organisation of plasma membrane receptors in general with the potential to link spatial organisation to function.

Cell membrane

10.3390/v13010142

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Citations (13)

Recognising the importance and impact of Imaging Scientists: Global guidelines for establishing career paths within core facilities

Journal of Microscopy (2024)

Graham Wright Kerry Thompson Yara Reis Johanna Bischof Philip E. Hockberger

Abstract In the dynamic landscape of scientific research, imaging core facilities are vital hubs propelling collaboration and innovation at the technology development and dissemination frontier. Here, we present a collaborative effort led by Global BioImaging (GBI), introducing international recommendations geared towards elevating the careers of Imaging Scientists in core facilities. Despite the critical role of Imaging Scientists in modern research ecosystems, challenges persist in recognising their value, aligning performance metrics and providing avenues for career progression and job security. The challenges encompass a mismatch between classic academic career paths and service‐oriented roles, resulting in a lack of understanding regarding the value and impact of Imaging Scientists and core facilities and how to evaluate them properly. They further include challenges around sustainability, dedicated training opportunities and the recruitment and retention of talent. Structured across these interrelated sections, the recommendations within this publication aim to propose globally applicable solutions to navigate these challenges. These recommendations apply equally to colleagues working in other core facilities and research institutions through which access to technologies is facilitated and supported. This publication emphasises the pivotal role of Imaging Scientists in advancing research programs and presents a blueprint for fostering their career progression within institutions all around the world.

Blueprint

Value (mathematics)

10.1111/jmi.13307

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Citations (8)