Other Seminars

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Fri 18 Jan 2019 from 08:00 to 09:00

Surgical Grand Rounds

John Radcliffe Academic, Lecture Theatre 1, Headington OX3 9DU

Communication in Healthcare: A Failure in Need of Rescue?

Professor Amir A. Ghaferi

Audience: Members of the University only

Organisers: Tarryn Ching

Fri 18 Jan 2019 from 09:15 to 10:15

MRC HIU Friday Morning Lab Meetings

MRC Weatherall Institute of Molecular Medicine, WIMM Seminar Room, Headington OX3 9DS

An essential role for the Zn2+ transporter ZIP7 in B cell development

Professor Richard Cornall

Audience: Members of the University only

Organisers: Anne Farmer

Fri 18 Jan 2019 from 11:00 to 12:00

Strubi seminars

Probing the mechanism of the SAMHD1 HIV-1 restriction factor

Dr Ian Taylor

SAMHD1 is a post-entry cellular restriction factor that inhibits HIV-1 replication in myeloid-lineage and resting CD4+ T cells. The mechanism of SAMHD1 restriction has been disputed but the predominant theory is that SAMHD1 dNTP triphosphohydrolase activity blocks HIV-1 infection by reducing the... Read more

SAMHD1 is a post-entry cellular restriction factor that inhibits HIV-1 replication in myeloid-lineage and resting CD4+ T cells. The mechanism of SAMHD1 restriction has been disputed but the predominant theory is that SAMHD1 dNTP triphosphohydrolase activity blocks HIV-1 infection by reducing the cellular dNTP pool to a level that does not support viral reverse transcription. A large body of structural and biochemical studies have demonstrated that the active form of SAMHD1 is a protein tetramer that contains four regulatory allosteric sites each accommodating a deoxynucleotide/nucleotide pair and four active sites that hydrolyse the dNTP substrates. In addition, other studies have shown that the dNTP triphosphohydrolysis reaction is regulated by tetramer stability, controlled by SAMHD1 phosphorylation at residue T592. However, although, this wealth of information has contributed significantly to our understanding of SAMHD1 restriction, regulation and activation the exact nature of SAMHD1 cellular activity that restricts HIV-1 and the molecular details catalytic mechanism of dNTP hydrolysis have remained unclear. Therefore, to elucidate the molecular mechanism of dNTP triphospho-hydrolysis by SAMHD1, we have undertaken virological studies together with comprehensive, enzymological studies employing deoxynucleotide substrate and activator analogues and determined crystal structures of catalytically active SAMHD1 with dNTP-mimicking, competitive inhibitors. The SAMHD1-inhibitor co-crystal structures show in atomic detail how dNTP substrates are coordinated at the SAMHD1 active site and reveal how the activated protein cleaves the phospho-ester bond in the dNTP substrate. In conclusion, these studies now clarify the anti-HIV-1 activity of SAMHD1 and provide the molecular details of the SAMHD1 reaction mechanism demonstrating how dNTP substrates are hydrolysed and enable more accurate prediction of whether new and existing antiviral and anticancer drugs are hydrolysed by SAMHD1.

Audience: Members of the University only

Organisers: Agata Krupa

Fri 18 Jan 2019 from 11:00 to 12:00

MRC HIU Wednesday Seminar Series

MRC Weatherall Institute of Molecular Medicine, WIMM Seminar Room, Headington OX3 9DS

Accessories to the crime: functions of immune cells in the tumor microenvironment

Dr Arianna Calcinotto

Audience: Members of the University only

Organisers: Anne Farmer

Fri 18 Jan 2019 from 13:00 to 14:00

DPAG Head of Department Seminar Series

Sherrington Building, Large Lecture Theatre, off Parks Road OX1 3PT

Adipose tissue expandability, lipotoxicity and the metabolic syndrome

Professor Antonio Vidal-Puig

The link between obesity and type 2 diabetes is clear on an epidemiological level, however the mechanism linking these two common disorders is not well defined. One hypothesis linking obesity to type 2 diabetes is the adipose tissue expandability hypothesis. The adipose tissue expandability... Read more

The link between obesity and type 2 diabetes is clear on an epidemiological level, however the mechanism linking these two common disorders is not well defined. One hypothesis linking obesity to type 2 diabetes is the adipose tissue expandability hypothesis. The adipose tissue expandability hypothesis states that a failure in the capacity for adipose tissue expansion, rather than obesity per se is the key factor linking positive energy balance and type 2 diabetes. All individuals possess a maximum capacity for adipose expansion which is determined by both genetic and environmental factors. Once the adipose tissue expansion limit is reached, adipose tissue ceases to store energy efficiently and lipids begin to accumulate in other tissues. Ectopic lipid accumulation in non-adipocyte cells causes lipotoxic insults including insulin resistance, apoptosis and inflammation. This article discusses the links between adipokines, inflammation, adipose tissue expandability and lipotoxicity. Finally, we will discuss how considering the concept of allostasis may enable a better understanding of how diabetes develops and allow the rational design of new anti diabetic treatments.

Audience: Members of the University only

Fri 18 Jan 2019 from 13:00 to 14:00

NDM Seminar Series

Henry Wellcome Building of Cellular and Molecular Physiology, Seminar Rooms A & B, Roosevelt Drive OX3 7BN

The genomics of cancer evolution and metastasis & The role of common genetic variants in cancer gene regulation

Dr David Wedge, Annabelle Lewis

Audience: Members of the University only

Organisers: Kathryn Smith

Mon 21 Jan 2019 from 12:00 to 13:00

Kennedy Institute Seminars

Kennedy Institute of Rheumatology, Bernard Sunley Theatre, Headington OX3 7LF

Circadian clock regulation of mucosal immunity

Professor David Ray

Recent studies reveal that airway epithelial cells are critical pulmonary circadian pacemaker cells, mediating rhythmic inflammatory responses. Using mouse models we now identify the rhythmic circadian repressor REV-ERB as essential to the mechanism coupling the pulmonary clock to innate... Read more

Recent studies reveal that airway epithelial cells are critical pulmonary circadian pacemaker cells, mediating rhythmic inflammatory responses. Using mouse models we now identify the rhythmic circadian repressor REV-ERB as essential to the mechanism coupling the pulmonary clock to innate immunity. Dual mutation of REV-ERBα and its paralog REV-ERBβ in bronchial epithelia further augmented inflammatory responses and chemokine activation, but also initiated a basal inflammatory state, revealing a critical homeostatic role for REV-ERB proteins in the suppression of the endogenous pro-inflammatory mechanism in un-challenged cells. Thus, dynamic changes in stability of REV-ERB protein couple the core clock to innate immunity. ---- David trained in general internal medicine and endocrinology in the UK, and California. He developed a research interest in nuclear receptor function in inflammation, which was supported by MRC, and GSK fellowships. He then identified the importance of the circadian clock machinery in regulating innate immunity, using lung, joint and gut models, and is extending these studies to human cohorts. He recently moved to Oxford, with Wellcome and MRC support, to work on circadian control of inflammation in the lung, and the re-wiring of circadian metabolism by chronic inflammatory processes.

Audience: Members of the University only

Organisers: Laura Sánchez Lazo

Mon 21 Jan 2019 from 13:00 to 14:00

WIMM Science Career Seminars

MRC Weatherall Institute of Molecular Medicine, Seminar Room, Headington OX3 9DS

CAREER SEMINAR: “Tales from our WIMM Job Club – University Teaching and Analytical Support to Industry”

Lucy Eddowes, Emma Jones

This month's seminar series will feature two great speakers. Dr. Emma Jones will talk to us about her work as a University lecturer and Dr. Lucy Eddowes will tell us about working in analytical support to the biomedical industry. Lucy and Emma will also tell us about the "Job Club" they set up... Read more

This month's seminar series will feature two great speakers. Dr. Emma Jones will talk to us about her work as a University lecturer and Dr. Lucy Eddowes will tell us about working in analytical support to the biomedical industry. Lucy and Emma will also tell us about the "Job Club" they set up whilst Postdocs at the WIMM, where they met regularly to discuss ideas and give each other feedback on their plans for next steps after they left the WIMM.

Audience: Members of the University only

Organisers: Natalia Sampaio

Tue 22 Jan 2019 from 12:00 to 13:00

CNCB Seminar Series

Oxford Martin School, Oxford Martin School, 34 Broad Street, 34 Broad Street OX1 3BD

Mind the Gap: Super-resolution Imaging of the Extracellular Space of the Brain

Valentin Nagerl

The advent of super-resolution microscopy has created unprecedented opportunities to study the mammalian central nervous system, which is dominated by anatomical structures whose nanoscale dimensions critically influence their biophysical properties. I will present our recent methodological... Read more

The advent of super-resolution microscopy has created unprecedented opportunities to study the mammalian central nervous system, which is dominated by anatomical structures whose nanoscale dimensions critically influence their biophysical properties. I will present our recent methodological advances 1) to analyze dendritic spines in the hippocampus in vivo and 2) to visualize the extracellular space (ECS) of the brain. Using a two-photon–STED microscope equipped with a long working distance objective and ‘hippocampal window’ to reach this deeply embedded structure, we measured the density and turnover of spines on CA1 pyramidal neurons. Spine density was two times higher than reported by conventional two-photon microscopy; around 40% of all spines turned over within 4 days. A combination of 3D-STED microscopy and fluorescent labeling of the extracellular fluid allows super-resolution shadow imaging (SUSHI) of the ECS in living brain slices. SUSHI enables quantitative analyses of ECS structure and produces sharp negative images of all cellular structures, providing an unbiased view of unlabeled brain cells in live tissue.

Audience: Members of the University only

Organisers: Fiona Woods

Tue 22 Jan 2019 from 13:00 to 14:00

Molecular Haematology Unit, WIMM

MRC Weatherall Institute of Molecular Medicine, Seminar Room, Headington OX3 9DS

The human centromere, a paradigm in chromatin-based epigenetic inheritance

Dr Lars Jansen

Audience: Members of the University only

Organisers: Liz Rose

Tue 22 Jan 2019 from 13:00 to 14:00

Population Health Seminars

Richard Doll Building, Lecture Theatre, Old Road Campus OX3 7LF

Richard Doll Seminar: Sustainable and healthy food systems - Now and in the future

Professor Alan Dangour

Audience: Members of the University only

Organisers: Graham Bagley

Thu 24 Jan 2019 from 13:00 to 14:00

Medical Grand Rounds

Horton Hospital / Rheumatology

Dr Lorraine O’Neill, Dr Alex Mentzer, Dr Ian Arnold, Dr Neil Stewart

Horton Hospital: "Stroke: The Heart of the Matter", Dr Alex Mentzer, Dr Ian Arnold and Dr Neil Stewart -- Rheumatology: "A Wolf in Sheeps Clothing", Dr Lorraine O’Neill -- Chair: Prof Chris Conlon

Horton Hospital: "Stroke: The Heart of the Matter", Dr Alex Mentzer, Dr Ian Arnold and Dr Neil Stewart -- Rheumatology: "A Wolf in Sheeps Clothing", Dr Lorraine O’Neill -- Chair: Prof Chris Conlon

Audience: Members of the University and NHS clinical staff.

Fri 25 Jan 2019 from 08:00 to 09:00

Surgical Grand Rounds

John Radcliffe Academic, Lecture Theatre 1, Headington OX3 9DU

Novel methods for predicting growth of AAAs in humans – an update from the OxAAA study

Dr Regent Lee

Audience: Members of the University only

Organisers: Tarryn Ching

Fri 25 Jan 2019 from 11:00 to 12:00

Strubi seminars

Wellcome Trust Centre for Human Genetics, Meeting rooms A & B, Headington OX3 7BN

"Cell shape formation controlled by cytoskeleton"

Dr Naoko Mizuno

Neurons are highly polarized cells whose shape is controlled by cytoskeleton networks. The formation of neuronal protrusions such as dendrites and axons is mediated by the dynamic nature of microtubules, and it is the basis of neuronal development. Particularly at axon branches, signaling processes... Read more

Neurons are highly polarized cells whose shape is controlled by cytoskeleton networks. The formation of neuronal protrusions such as dendrites and axons is mediated by the dynamic nature of microtubules, and it is the basis of neuronal development. Particularly at axon branches, signaling processes trigger actin re-formation leading to the recruitment of microtubules to reinforce the branching site; however, little is known about this remodeling mechanism. Combining the interdisciplinary methods of cryo-EM, biophysics, and cell biology, we focus on elucidating the mechanism of neuronal cell shape formation and accompanying cytoskeleton remodeling. We will present our recent discovery of a novel factor SSNA1, promoting axon branch formation. To understand the underlying mechanism of branch promotion, we have characterized the interaction of the protein with tubulin and reconstituted its microtubule nucleation process in vitro. Moreover, cryo-EM revealed the surprising observation that SSNA1 facilitates direct microtubule branching. Mutagenesis experiments in primary neurons correlate the molecular remodeling activity with the formation of axon branches.

Audience: Members of the University only

Organisers: Agata Krupa

Fri 25 Jan 2019 from 13:00 to 14:00

DPAG Head of Department Seminar Series

Sherrington Building, Large Lecture Theatre, off Parks Road OX1 3PT

An architectonic type principle integrates cerebral cortical architecture and connectivity

Prof. Dr Claus Hilgetag

The connections that link neurons within as well as between cerebral cortical areas form a multi-scale structural network for communication in the brain. Which principles underlie the organisation of this complex network? We addressed this question by systematically investigating the relation of... Read more

The connections that link neurons within as well as between cerebral cortical areas form a multi-scale structural network for communication in the brain. Which principles underlie the organisation of this complex network? We addressed this question by systematically investigating the relation of essential features of cortico-cortical connections, such as their presence or absence as well as patterns of laminar projection origins and terminations, to fundamental structural parameters of cortical areas, such as their distance, similarity in cortical cytoarchitecture as defined by cortical lamination or neuronal density, and similarity in further macroscopic and microscopic morphological features. These systematic analyses demonstrate the presence of an architectural type principle. Across different species (mouse, cat, macaque monkey and human) and different cortices, the essential features of cortico-cortical connections vary consistently and strongly with the cytoarchitectonic similarity of cortical areas. By contrast, such relations were not found as consistently in multivariate analyses for distance, similarity of cortical thickness or cellular morphological features. The presence of the architectonic type principle across mammalian brains allows direct cross-species predictions of the existence and laminar patterns of projections, including for the human brain, where such data are not directly available experimentally. Moreover, intrinsic brain architecture as characterised by architectural type and neural density also accounts for cellular neuronal features, such as cell size or shape. Thus, these findings illuminate a general principle of neural wiring and integrate cortical connectivity and architecture across scales of organisation, with implications for models of cortical physiology as well as developmental mechanisms.

Audience: Members of the University only

Mon 28 Jan 2019 from 11:00 to 12:00

Department of Oncology

Old Road Campus Research Building, Meeting rooms 71 a,b,c, Headington OX3 7DQ

Publishing and Careers at Nature Research

Dr Anne Mirabella

Audience: Members of the University only

Organisers: Amanda O'Neill

Mon 28 Jan 2019 from 12:00 to 13:00

Kennedy Institute Seminars

Kennedy Institute of Rheumatology, Bernard Sunley Theatre, Headington OX3 7LF

Title TBC

Prof Gillian Griffiths

Audience: Members of the University only

Organisers: Laura Sánchez Lazo

Mon 28 Jan 2019 from 14:00 to 15:00

BDI seminars

Big Data Institute, Seminar room 0, Old Road Campus OX3 7LF

CKB Seminar: Using genetics to explore the consequences of obesity

Dr Jess Tyrrell

Audience: Members of the University only

Organisers: Graham Bagley

Tue 29 Jan 2019 from 13:00 to 14:00

Population Health Seminars

Richard Doll Building, Lecture Theatre, Old Road Campus OX3 7LF

Richard Doll Seminar: Incorporating biomarkers into breast cancer trials - where are we at?

Audience: Members of the University only

Organisers: Graham Bagley

Wed 30 Jan 2019 from 13:30 to 14:30

MRC HIU Wednesday Seminar Series

MRC Weatherall Institute of Molecular Medicine, WIMM Seminar Room, Headington OX3 9DS

Uncovering the enigmatic role of IL-33 in GI inflammation and cancer

Professor Theresa Pizarro

Audience: Members of the University only

Organisers: Anne Farmer