Other Seminars

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Mon 4 Sep 2017 from 10:30 to 11:30

Nuffield Department of Primary Care Health Sciences - Department research seminars

St Luke's Chapel, Woodstock Road OX2 6GG

Evidence in a post-truth world

Professor Trish Greenhalgh

The ‘post-truth world’ has been defined as “relating to or denoting circumstances in which objective facts are less influential in shaping public opinion than appeals to emotion and personal belief.” (Oxford English Dictionary, 2016). The rise of ‘post-truth’ requires us to go beyond... Read more

The ‘post-truth world’ has been defined as “relating to or denoting circumstances in which objective facts are less influential in shaping public opinion than appeals to emotion and personal belief.” (Oxford English Dictionary, 2016). The rise of ‘post-truth’ requires us to go beyond the question of how robust the evidence is and consider how persuasive it is to audiences who are seeking not facts but comforting myths. Notwithstanding the need for robust evidence, what else can scientists do (and with whom do we need to collaborate) to engage and influence public, press and politicians at a time when our own credibility in their eyes is low and falling? This lecture will provide an academic overview of why ‘post-truth’ is such a defining feature of our times and what we as scientists can do to help ensure that our evidence-based findings have impact despite prevailing anti-science societal forces.

Audience: Members of the University only

Organisers: Prof. Trish Greenhalgh

Tue 5 Sep 2017 from 13:00 to 14:00

Molecular Haematology Unit, WIMM

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

Metabolism, control of cell fate decisions, and stem cell renewal

Dr Keisuke Ito

Audience: Members of the University only

Organisers: Liz Rose

Wed 6 Sep 2017 from 08:00 to 17:00

Kennedy Institute Seminars

Trinity College, Speakers and registration details to be announced, Broad Street OX1 3BH

From the Laboratory to the Clinic: Immune-Tissue Cell Interactions

From the Laboratory to the Clinic is a translational research meeting, run annually since 1984 by an international organising committee led by the Directors of the Kennedy Institute, Professor Sir Marc Feldmann, Professor Sir Ravinder Maini and Professor Fiona Powrie. The meeting brings together... Read more

From the Laboratory to the Clinic is a translational research meeting, run annually since 1984 by an international organising committee led by the Directors of the Kennedy Institute, Professor Sir Marc Feldmann, Professor Sir Ravinder Maini and Professor Fiona Powrie. The meeting brings together basic scientists, clinicians, and industry researchers to explore how the latest discoveries in immunology and molecular medicine can be applied to improve clinical medicine. ORGANISING COMMITTEE Marc Feldmann (University of Oxford, UK) Ravinder Maini (Imperial College London, UK) Andrew McMichael (University of Oxford, UK) Fiona Powrie (University of Oxford, UK) Lawrence Steinman (Stanford University, USA) Jim Woody (Latterell Venture Partners, USA) Vincenzo Cerundolo (University of Oxford, UK) Rupert Vessy (Celgene, USA) TOPICS: Neuroimmunology Metabolism Tissue Repair and Regeneration Macrophage Heterogeneity and Function Vaccines Microbiome

Booking Required

Audience: Members of the University only

Wed 6 Sep 2017 from 10:00 to 11:00

Kennedy Institute Seminars

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

Immune Checkpoint Deficiencies in Large Vessel Vasculitis

Cornelia M. Weyand, MD, PhD

Dr. Weyand has a special interest in tissue-damaging immune responses in rheumatoid arthritis and large vessel vasculitis. She and her collaborators have established several preclinical models of autoimmune inflammation, including a chimera model in which human synovial tissue and human blood... Read more

Dr. Weyand has a special interest in tissue-damaging immune responses in rheumatoid arthritis and large vessel vasculitis. She and her collaborators have established several preclinical models of autoimmune inflammation, including a chimera model in which human synovial tissue and human blood vessels are engrafted into immunodeficient mice. In these model systems, Dr. Weyand’s research team has defined the role of T cells and dendritic cells in deviating from protective to destructive immunity. Over the last decade, she has devoted special emphasis to the remodeling of the immune system with aging, how chronic disease ages the immune system, and how aged immune cells cause inflammation. This studies have identified molecular defects in metabolic programming and in DNA damage responses that render T cells tissue-invasive and pro-inflammatory. In recent work, she and her team have implicated defects in immuno-protective checkpoints in the breakdown of the arterial wall immunoprivilege, connecting the overall threshold setting of the immune system to organ-specific autoimmune disease.

Audience: Members of the University only

Organisers: Gintare Kolesnikovaite

Thu 7 Sep 2017 from 10:00 to 11:00

BDI seminars

Big Data Institute, BDI LG Seminar Room 0, Old Road Campus OX3 7LF

BDI Seminar: Genomics and drug discovery

Dr John Whittaker

I will discuss the use of genomics and data science in drug discovery at GSK, and particularly in the selection and validation of drug targets. I’ll highlight the interplay between experimental science and informatics, and will discuss recently published work highlighting the value of genetic... Read more

I will discuss the use of genomics and data science in drug discovery at GSK, and particularly in the selection and validation of drug targets. I’ll highlight the interplay between experimental science and informatics, and will discuss recently published work highlighting the value of genetic information in selecting drug targets/indications. Motivated by this, I will also include a sketch of work ongoing and planned in this area at GSK, particularly with respect to the potential to integrate electronic health record and genomics information. I will also describe work at Open Targets (https://www.targetvalidation.org/), including both experimental and informatics aspects. I will focus on the key concepts and avoid technical detail, both regarding genomics and data science.

Audience: Members of the University only

Organisers: Natasha Bowyer

Thu 7 Sep 2017 from 10:30 to 11:30

Nuffield Department of Primary Care Health Sciences - Department research seminars

St Luke's Chapel, Woodstock Road OX2 6GG

Different dimensions of congenital heart disease: 2D images, 3D models, and the experiential domain

Dr Giovanni Biglino

This talk is by visiting scholar Dr Giovanni Biglino, a bioengineer with an interest in medical humanities, currently based at the University of Bristol. He makes 3-D models of the hearts of children with congenital heart disease and collects narratives from the parents, allowing interdisciplinary... Read more

This talk is by visiting scholar Dr Giovanni Biglino, a bioengineer with an interest in medical humanities, currently based at the University of Bristol. He makes 3-D models of the hearts of children with congenital heart disease and collects narratives from the parents, allowing interdisciplinary co-design of new approaches to imaging and treatment. In this talk, he explores three different sources of information and insight: a 2-dimensional image of the affected heart; a 3-dimensional model of the same heart; and the narratives of parents whose children have congenital heart disease. He will explore how these different sources can be combined in a co-design approach to improve the investigation and management of this condition. The seminar: An exploration of the dimensionality of the heart, describing different approaches that can increase our insight into the organ (particularly in the presence of congenital heart disease). Analyses based on two-dimensional data derived from cardiovascular magnetic resonance imaging (MRI) can provide functional information, including knowledge of changes in ventriculo-arterial coupling, which can be gathered by applying wave intensity analysis to the MRI data. Three-dimensional data can also be extracted to manufacture replicas of patients’ hearts and vessels by means of 3D printing technology, which can have a wide range of applications, from training medical staff to potentially aid in the decision-making process when discussing surgical/interventional strategies. Finally, the experiential dimension should also be considered and opens the door to taking into account the narrative of patients, leading to co-creating original artworks. The speaker: Giovanni Biglino is a biomedical engineer. He studied at Imperial College London and obtained his PhD in cardiovascular mechanics from the Brunel Institute of Bioengineering. He has carried out research at Great Ormond Street Hospital for children and University College London, with the cardiac engineering team, focusing on congenital heart disease. Now he is a Lecturer in Cardiovascular Bioinformatics and Medical Statistics at the Bristol Heart Institute. He has studied biostatistics at Harvard Medical School and has started to enthusiastically explore the world of narrative medicine at Columbia University. His current research is very collaborative, involving cardiologists, surgeons, imagers, psychologists and artists.

Audience: Colleagues from Humanities Department welcome

Thu 7 Sep 2017 from 16:30 to 17:30

Experimental Medicine TGU Seminars

John Radcliffe Hospital - Main Building, GPEC Level 3 Seminar Room 2B, Headington OX3 9DU

Metabolic profiling of IBD to improve diagnosis and treatment

Sandrine Claus

Sandrine Claus, Associate Professor in Integrative Metabolism, Dept. of Food & Nutritional Sciences, The University of Reading

Sandrine Claus, Associate Professor in Integrative Metabolism, Dept. of Food & Nutritional Sciences, The University of Reading

Audience: Public

Organisers: Prof Holm Uhlig

Fri 8 Sep 2017 from 11:00 to 12:00

BDI seminars

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

BDI seminar: Novel methods for the comprehensive analysis of physical activity in epidemiology

Louise Millard

To date, analysis of physical activity has focused on the use of a small number of simple summary statistics derived from uni-axial accelerometer data, such as the mean level of activity. These statistics only capture a small portion of the information in this data. Furthermore, higher-resolution... Read more

To date, analysis of physical activity has focused on the use of a small number of simple summary statistics derived from uni-axial accelerometer data, such as the mean level of activity. These statistics only capture a small portion of the information in this data. Furthermore, higher-resolution tri-axial accelerometer data is now available in UK Biobank, in circa 100,000 participants. There is a need to develop methods to more comprehensively characterise patterns in these data, in order to investigate which aspects of activity relate to other traits and disease. In this talk I will present my initial work in this area, including a novel 'activity bigrams' approach that characterises how a person’s activity changes from one moment to the next. Activity bigrams can, for instance, differentiate between two people with the same time in moderate activity, where one person often stays in moderate activity from one moment to the next and the other does not. We tested the association of activity bigrams with body mass index (BMI), as an exemplar, and identified several associations. For instance, a lower number of consecutive minutes in sedentary then moderate activity coupled with a higher number of consecutive minutes in moderate then vigorous activity was associated with a lower BMI, even after accounting for the amount of time spent in sedentary, low, moderate and vigorous activity overall.

Audience: Members of the University only

Organisers: Natasha Bowyer

Mon 11 Sep 2017 from 12:00 to 13:00

Kennedy Institute Seminars

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

A journey through the lymphatic vasculature: what turns neutrophils on?

Dr Mathieu-Benoit Voisin PhD

Mathieu-Benoit Voisin graduated in 2000 from the University of Bordeaux II (France) in Biological Sciences with a specialisation in Immunology. He obtained his PhD from the University of Tours (France) in 2003 and conducted post-doctoral research with Prof. Nourshargh at Imperial College London. In... Read more

Mathieu-Benoit Voisin graduated in 2000 from the University of Bordeaux II (France) in Biological Sciences with a specialisation in Immunology. He obtained his PhD from the University of Tours (France) in 2003 and conducted post-doctoral research with Prof. Nourshargh at Imperial College London. In 2007, he relocated to the William Harvey Research Institute and is currently establishing his own independent research programme studying the lymphatic system. Neutrophils are key effectors of the innate immune response but can also contribute to the development of many acute inflammatory diseases. There is also evidence for neutrophil involvement in the regulation of the adaptive immunity and the pathogenesis of numerous chronic inflammatory conditions such as rheumatoid arthritis. The precise role of neutrophils in this autoimmune disorder is unclear and the focus of my research is to elucidate the mechanisms of neutrophil migration into lymphatic vessels and lymph nodes following antigen-induced arthritis and their role in the regulation of the acquired immunity. The main hypothesis is that neutrophil entry into lymphatic vessels plays an important role in the initiation of autoimmune diseases by changes in their phenotypes and their entry to the lymphatic vascular system. The project thus aims to characterize the mechanisms of neutrophil/lymphatic vessel interactions in vivo as analysed by intravital confocal microscopy and the implications of this response to the development of autoimmune pathologies. Collectively, the project will address a previously unexplored aspect of leukocyte biology and chronic disorders thus making a significant and novel contribution to the field of acute & chronic inflammation.

Audience: Members of the University only

Organisers: Dr Nikki Horwood

Tue 12 Sep 2017 from 13:00 to 14:00

Molecular Haematology Unit, WIMM

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

Dynamic remodelling of the haematopoietic stem cell niche

Dr Owen Tamplin

Audience: Members of the University only

Organisers: Liz Rose

Tue 12 Sep 2017 from 16:00 to 17:00

OPDC Seminar Series (DPAG)

Le Gros Clark Building, Lecture Theatre, Le Gros Clark Building, DPAG, off South Parks Road OX1 3QX

Of genes and mechanisms: cell biology of PD

Dr Mattia Volta

Dr. Volta received his B.Sc.in Medicinal Chemistry and subsequently a Ph.D. in Molecular Pharmacology and Oncology at the University of Ferrara in Italy. As an undergraduate student, Dr. Volta was involved in the study of the pathophysiology of Parkinson’s Disease, especially through behavioral... Read more

Dr. Volta received his B.Sc.in Medicinal Chemistry and subsequently a Ph.D. in Molecular Pharmacology and Oncology at the University of Ferrara in Italy. As an undergraduate student, Dr. Volta was involved in the study of the pathophysiology of Parkinson’s Disease, especially through behavioral and neurochemical investigations. During these early years, he focused on the investigation of the opioid receptors system in rodent PD-models. Later, during his Ph.D. studies, he became interested in the study and characterization of transgenic animals carrying PD-related genetic modifications. Dr. Volta’s main research interest and passion is to study and better understand how key neuronal proteins interact at the circuit level and what dysfunction(s) may ultimately cause disease in the human brain. http://www.eurac.edu/en/aboutus/people/pages/staffdetails.aspx?persId=37823

Audience: Members of the University only

Organisers: Melanie Witt

Thu 14 Sep 2017 from 11:00 to 12:00

Ludwig Institute Seminar Series

NDM Building, TDI, Basement meeting room, NDM Research Building, Headington OX3 7FZ

Ascorbate regulates stem cell function and leukemogenesis

Dr Michalis Agathocleous

Stem cell fate can be influenced by metabolite levels in culture but it is unknown whether physiological variations in metabolite levels regulate stem cell function within normal tissues. We developed a metabolomics method for analysis of rare cell populations isolated directly from tissues and... Read more

Stem cell fate can be influenced by metabolite levels in culture but it is unknown whether physiological variations in metabolite levels regulate stem cell function within normal tissues. We developed a metabolomics method for analysis of rare cell populations isolated directly from tissues and used it to compare haematopoietic stem cells (HSCs) to restricted haematopoietic progenitors. Each haematopoietic cell type had a distinct metabolic signature. Human and mouse HSCs had unusually high levels of ascorbate, which declined with differentiation. Systemic or cell autonomous ascorbate depletion in mice increased HSC frequency and function and promoted myelopoiesis. Ascorbate regulated HSC function in part through Tet2, a dioxygenase tumor suppressor enzyme. Ascorbate depletion cooperated with Flt3ITD leukaemic mutations to accelerate leukaemogenesis, and this was reversed by dietary ascorbate. Therefore physiological variations in ascorbate levels in vivo regulate Tet activity, regeneration and leukaemogenesis.

Audience: Members of the University only

Organisers: Christina Woodward

Thu 14 Sep 2017 from 11:00 to 12:00

BDI seminars

Big Data Institute, BDI LG Seminar Room 0, Old Road Campus OX3 7LF

BDI Seminar: Prospects of fine-mapping trait-associated genomic regions using summary statistics from genome-wide association studies

Christian Benner

During the last two years, genetics research has seen a surge of computational approaches that work directly on summary data from Genome-Wide Association Studies (GWAS) to avoid privacy concerns and logistics of sharing individual-level genotype data and to cope with ever increasing sample sizes.... Read more

During the last two years, genetics research has seen a surge of computational approaches that work directly on summary data from Genome-Wide Association Studies (GWAS) to avoid privacy concerns and logistics of sharing individual-level genotype data and to cope with ever increasing sample sizes. Recently, fine-mapping approaches for identifying causal variants have been extended to use GWAS summary data (CAVIAR, CAVIARBF, PAINTOR). Common to these approaches is that they rely on computationally expensive exhaustive search restricting their use to only a few hundred variants. Although all these approaches require information about the Linkage Disequilibrium (LD) between variants, there has not been a comprehensive evaluation of how estimation of the LD structure from reference genotype panels performs compared to the original individual-level GWAS data. We introduce a software package FINEMAP that replaces the exhaustive search by an ultrafast stochastic search. We demonstrate that (1) FINEMAP opens up completely new opportunities by fine-mapping the HDL-C association of the LIPC locus with 20,000 variants in less than 90 seconds while exhaustive search would require thousands of years. By jointly modeling the whole locus, (2) FINEMAP can identify more plausible variant combinations than standard conditional analysis. At the LIPC locus we identify a 3-SNP configuration with 190-fold higher likelihood than the top configuration from conditional analysis. We suggest that a missense variant and a promoter polymorphism are likely to be causal whereas the lead variant in single-SNP testing has less evidence than a regulatory variant correlated with it. With extensive simulations we further show that (3) FINEMAP is as accurate as exhaustive search when the latter can be completed and (4) achieves even higher accuracy when the latter must be restricted due to computational reasons. We also report important practical results showing that a reference panel size of 1,000 individuals from the target population is adequate for a GWAS cohort size of up to 10,000 individuals, whereas smaller panels, such as those from the 1000 Genomes Project, should be avoided. We also show, both theoretically and empirically, that the size of the reference panel needs to scale with the GWAS sample size, which has important consequences for the application of these methods in ongoing GWAS meta-analyses and large biobank studies. Our results are based on comprehensive simulations with UK biobank data and Finnish cohorts over 100 GWAS regions from coronary artery disease, Crohn’s disease, lipids, schizophrenia and type 2 diabetes and on Finnish data of the APOE locus that we fine-map in detail discovering a novel variant associated with LDL-C. Christian Benner (joint work with Matti Pirinen)

Audience: Members of the University only

Organisers: Graham Bagley

Fri 15 Sep 2017 from 12:00 to 13:00

WHG High Profile Seminars

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

Genomics-Driven Biomarker Discovery at CHOP and Utility in Therapeutic Development and Patient Care

Professor Hakon Hakonarson

This talk will focus on genomic strategies applied in academia to identify subsets of patients who, based on their genetic make-up, are predicted to have a favorable response profile to drugs that modify specific pathways and gene networks. Examples will be given on attention deficit hyperactivity... Read more

This talk will focus on genomic strategies applied in academia to identify subsets of patients who, based on their genetic make-up, are predicted to have a favorable response profile to drugs that modify specific pathways and gene networks. Examples will be given on attention deficit hyperactivity disorder and autism, where a subset of patients were identified with copy number deletion in the metabotropic glutamate receptor signaling pathway, where a drug candidate, already developed through phase III for a different indication was repurposed for these new indications. Another genetically stratified patient cohort with inflammatory bowel disease is also being studied for intervention at a novel site in the TNF alpha pathway observed through genetic associations where functionally active rare variants are being implicated in the disease pathogenesis with potential extension to other autoimmune diseases. A few rare disease examples will be discussed where new discoveries have led to repurposing opportunities based on state-of-the-art genomic approaches.

Audience: Members of the University only

Organisers: Isabel Schmidt

Fri 15 Sep 2017 from 12:00 to 13:00

CNCB Seminar Series

Oxford Martin School, Old Indian Institute, 34 Broad Street, Oxford , 34 Broad Street OX1 3BD

Genetic Dissection of Animal Locomotion

Richard Mann

All animal behaviors depend on engaging the motor system. Yet, despite its central importance, we know very little about how the motor system is engaged by nervous systems to generate highly rhythmic locomotor behaviors, such as walking. Moreover, the same motor systems that are used for walking... Read more

All animal behaviors depend on engaging the motor system. Yet, despite its central importance, we know very little about how the motor system is engaged by nervous systems to generate highly rhythmic locomotor behaviors, such as walking. Moreover, the same motor systems that are used for walking have the remarkable facility to be reconfigured in a wide variety of ways, for example, to allow animals to run, jump, or scratch an itch. Our long-term goal is to understand how animal nervous systems produce such distinct motor outputs using the same set of motor neurons and muscles, with a focus on locomotion. We study this problem in the fruit fly because of its powerful genetic tools and complex—but not too complex—set of behaviors and nervous system. In my talk, I will describe our efforts to develop high resolution assays to study locomotion in the fruit fly, our recent attempts to genetically dissect this neural circuitry, and how a common motor ground plan can be modified by neuromodulators to execute alternate types of related motor outputs. I may also describe our efforts to dissect the development of the motor system, since how it is constructed may provide important insights into how it functions.

Audience: Members of the University only

Organisers: Fiona Woods

Fri 15 Sep 2017 from 14:00 to 15:00

Jenner Seminars

Kennedy Institute of Rheumatology, Lecture Theatre, Headington OX3 7LF

* CANCELLED * Seminar Cancelled (Amino acid degrading enzymes and their role in tumour immune escape mechanisms)

Prof Vincenzo Cerundolo

Audience: Members of the University only

Organisers: Lisbeth Soederberg

Fri 15 Sep 2017 from 14:00 to 15:00

Peter Medawar Building Seminars

Medawar Building, Please note the Medawar Building has no reception. If you wish to attend the seminar you will need to call 281231 on arrival for entry., off South Parks Road OX1 3SY

Use of network theory to define optimal HIV immune targets: Implications for immunologic control and immunogen design

Professor Bruce Walker

Viral diversity remains a major challenge to HIV vaccine development. By applying concepts rooted in network theory to viral protein structure, we have developed an algorithm that identifies amino acid residues critical to the structure and function of HIV proteins. Functional data from persons who... Read more

Viral diversity remains a major challenge to HIV vaccine development. By applying concepts rooted in network theory to viral protein structure, we have developed an algorithm that identifies amino acid residues critical to the structure and function of HIV proteins. Functional data from persons who control HIV without medication demonstrate preferential CD8+ T cell recognition of highly networked residues predicted by the algorithm. Application of this knowledge to inform a rational T cell-based vaccine for HIV will be discussed.

Audience: Members of the University only

Organisers: Prof. Philip Goulder

Mon 18 Sep 2017 from 11:00 to 12:00

Department of Oncology

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

Mon 18 Sep 2017 from 12:00 to 13:00

Kennedy Institute Seminars

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

Patching up the crypt: Innate immune cells orchestrate intestinal regeneration

Associate Professor Tom Cupedo

Tom Cupedo is an associate professor at the department of Hematology at the Erasmus University Medical Center in Rotterdam, The Netherlands. He did his training as a PhD student with Reina Mebius, investigating ILC3 in mouse lymph node development and as a postdoctoral fellow with Hergen Spits,... Read more

Tom Cupedo is an associate professor at the department of Hematology at the Erasmus University Medical Center in Rotterdam, The Netherlands. He did his training as a PhD student with Reina Mebius, investigating ILC3 in mouse lymph node development and as a postdoctoral fellow with Hergen Spits, leading to the identification of human fetal ILC3. In recent years his research has been focused on the biology of group 3 Innate lymphoid Cells (ILC3), especially in the context of intestinal regeneration. Recent findings include the characterization of a stromal niche for ILC3 in human and mouse lymph nodes, and the discovery of an important role for ILC3 as regulators of epithelial stem cell regeneration and tissue repair following intestinal damage.

Audience: Members of the University only

Organisers: Gintare Kolesnikovaite

Mon 18 Sep 2017 from 15:00 to 16:00

BDI seminars

Big Data Institute, BDI LG Seminar Room 0, Old Road Campus OX3 7LF

BDI Seminar: A Bayesian model-based approach to finding cell-type level associations in heterogeneous methylation samples

Daniel W Kennedy

Epigenome-wide association studies are often performed using heterogeneous methylation samples, especially when there is no prior information as to which cell-types are disease associated. While much work has been done on estimating cell-type fractions and removing cell-type heterogeneity... Read more

Epigenome-wide association studies are often performed using heterogeneous methylation samples, especially when there is no prior information as to which cell-types are disease associated. While much work has been done on estimating cell-type fractions and removing cell-type heterogeneity variation, relatively little work has been done on identifying cell-type specific variation in heterogeneous samples. In this talk I present a Bayesian model-based approach for making cell-type specific inferences in heterogeneous settings, by utilising a logistic transform to properly constrain parameters, and incorporating a prior knowledge of cell-type lineage via prior covariance structure. The approach was applied to the determination of sex-specific cell-type effects in methylation, where cell-type information was present as an independent verification of the results. The approach showed significant improvement in performance over previously used methods, particularly for detecting association in several rare cell-types. I outline current and future work on this problem, which leverages the flexibility of the Bayesian modelling approach by incorporating local methylation correlation and multiple data-types.

Audience: Members of the University only

Organisers: Natasha Bowyer

Tue 19 Sep 2017 from 11:30 to 12:30

Population Health Seminars

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

NPEU Seminar: Antenatal interventions to improve pregnancy outcomes - do they work?

Fionnuala McAuliffe

Audience: Members of the University only

Organisers: Graham Bagley

Tue 19 Sep 2017 from 12:00 to 12:45

WIMM Occasional Seminars

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

The biology of ELTD1/ADGRL4: a novel regulator of tumour angiogenesis

David Favara

Audience: Members of the University only

Organisers: Liz Rose

VIVA SEMINAR

Tue 19 Sep 2017 from 13:00 to 14:00

Molecular Haematology Unit, WIMM

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

Development, maintenance and function of tissue resident macrophages

Dr Elisa Gomez Perdiguero

Audience: Members of the University only

Organisers: Liz Rose

Wed 20 Sep 2017 from 10:30 to 11:30

Nuffield Department of Primary Care Health Sciences - Department research seminars

St Luke's Chapel, Woodstock Road OX2 6GG

OPTIMUM: Optimising Titration and Monitoring of Maternal Blood Pressure

Louise Pealing

Audience: Members of the University only

Wed 20 Sep 2017 from 13:00 to 14:00

SGC Seminars

NDM Building, TDI Basement seminar room, Headington OX3 7FZ

Global Biochemical Profiling for Problem Solving in Biology and Disease

Prof Chris Schofield

Towards New Antibiotics – Targeting Penicillin Binding Proteins The lecture will begin by giving some thoughts on possible reasons as to why β-lactams remain the most important antibacterials after more than 70 years of use. Mechanisms of resistance to the β-lactams will be described, focussing... Read more

Towards New Antibiotics – Targeting Penicillin Binding Proteins The lecture will begin by giving some thoughts on possible reasons as to why β-lactams remain the most important antibacterials after more than 70 years of use. Mechanisms of resistance to the β-lactams will be described, focussing on the β-lactamases. A review of attempts to develop non β-lactams targeting the penicillin binding protein (PBP) targets of β-lactams and β-lactamases will be given. Work aimed at the development of single compounds targeting PBPs and both metallo and serine β-lactamases will be described.

Audience: Members of the University only

Organisers: Natsumi Astley

Thu 21 Sep 2017 from 11:00 to 12:30

Population Health Seminars

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

Ethox Seminar: Zika and the failure to act under the police power

Jacqueline Fox

Zika is a mosquito-borne and sexually transmitted disease that is a dangerous threat to pregnant women, causing catastrophic birth defects in a large percentage of fetuses when their mothers become infected while pregnant. It raises numerous issues related to abortion, birth control, poverty,... Read more

Zika is a mosquito-borne and sexually transmitted disease that is a dangerous threat to pregnant women, causing catastrophic birth defects in a large percentage of fetuses when their mothers become infected while pregnant. It raises numerous issues related to abortion, birth control, poverty, and women’s control over their procreative choices. While the United States received ample warning from January 2016 onward that it was at risk of local transmission of this virus and public health officials at all levels generally behaved properly, the state and federal legislative responses in the summer of 2016 were entirely inadequate. For example, no state at a high level of risk undertook to provide long lasting and reliable birth control to all women who wanted it. Furthermore, Congress took a seven-week recess at the height of mosquito season without providing any funding for a Zika response. In light of these failures, it appears that the federalist system that allocates both public health police powers and duties to act contains a flaw. The system creates a vacuum within which there are no enforcement mechanisms that can compel legislators to act appropriately. Given recent changes in the United States political make up at a federal level, it appears that the problems are only going to get worse. This talk will analyze the response from January through August 2016 from a legal, health policy, and ethical framework and frame this analysis within current challenges. An article by Jacqueline Fox concerning this case study has recently been published in the Connecticut Law Review. Bookings: If you would like to attend, please email jane.beinart@ethox.ox.ac.uk

Booking Required

Audience: Members of the University only

Organisers: Graham Bagley

Fri 22 Sep 2017 from 09:15 to 10:15

MRC HIU Friday Morning Lab Meetings

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

En route to deep profiling of tumour-specific MHC-associated peptidomes by mass spectrometry

Dr Nicola Ternette

Audience: Members of the University only

Organisers: Anne Farmer

Fri 22 Sep 2017 from 13:00 to 14:00

WIMM Occasional Seminars

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

“Insights into Hematopoiesis and Aging from the Rhesus Macaque Model”

Cynthia Dunbar

Audience: Members of the University only

Organisers: Sarah Butler

Mon 25 Sep 2017 from 12:00 to 14:00

Centre for Personalised Medicine Seminars

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

Pushing forward the limit of plasma DNA-based molecular diagnostics

Professor Dennis Lo

Booking Required

Audience: Members of the University only

Organisers: Catherine Lidbetter

The Centre for Personalised Medicine is delighted to invite you to a talk by Professor Dennis Lo, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong: Pushing forward the limit of plasma DNA-based molecular diagnostics The talk will take place on Monday 25th September at 12pm in Rooms A & B at The Wellcome Trust Centre for Human Genetics. Lunch will follow from 1 – 2pm. Email cpm@well.ox.ac.uk if you have any questions.

Mon 25 Sep 2017 from 13:00 to 14:00

WIMM MONDAY SEMINARS

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

The role of miRNA haploinsufficiency in MDS pathogenesis

Dr Aly Karan

Audience: Members of the University only

Organisers: Linda Roberts

Tue 26 Sep 2017 from 11:00 to 12:00

SGC Seminars

NDM Building, TDI Basement seminar room, Headington OX3 7FZ

Phosphorylation-dependent assembly of DNA damage response complexes’

Prof Laurence Pearl

Abstract: Coordination of the cellular response to DNA damage is organised around a set of large multi-domain ‘scaffold’ proteins, including BRCA1, MDC1, 53BP1 and TOPBP1, which recognise post-translational modifications such as phosphorylation, methylation and ubiquitylation on other proteins,... Read more

Abstract: Coordination of the cellular response to DNA damage is organised around a set of large multi-domain ‘scaffold’ proteins, including BRCA1, MDC1, 53BP1 and TOPBP1, which recognise post-translational modifications such as phosphorylation, methylation and ubiquitylation on other proteins, and are themselves carriers of such regulatory signals. My laboratory is studying how these post-translational modification, especially phosphorylation, provide the signals for assembly of the multi-protein complexes that mediate DNA damage signalling and repair. I will discuss published work on assembly of the DNA damage checkpoint complex, and present new data on a phosphorylation-dependent collaboration between 53BP1 and TOPBP1 that has a major regulatory role in preventing replication in the presence of DNA damage. Short Bio: Laurence Pearl is Professor of Structural Biology in the Genome Damage and Stability Centre at the University of Sussex, where he was Head of the School of Life Sciences from 2009 to 2017. For the 10 years before that he was Chairman of the Section of Structural Biology at the Institute of Cancer Research in London. His laboratory studies the structural biology of the DNA Damage Response and the HSP90 molecular chaperone system, and seeks to translate these basic studies for the development of new drugs for the treatment of cancer and other diseases. He is a Wellcome Trust Senior Investigator, a Fellow of the Royal Society (FRS), a Fellow of the Academy of Medical Sciences (FMedSci) and an elected member of the European Molecular Biology Organisation (EMBO) and the Academia Europeae. In 2013 he shared the CR-UK Translational Cancer Research Prize (with Paul Workman, ICR) for uncovering HSP90 as a novel target in cancer therapy and for the development of the leading HSP90 inhibitor, AUY922. He was awarded the 2018 Novartis Medal and Prize by the Biochemical Society

Audience: Members of the University only

Organisers: Natsumi Astley

Tue 26 Sep 2017 from 12:00 to 13:00

Nuffield Department of Primary Care Health Sciences - Department research seminars

External validation of clinical prediction models using big data from e-health records or IPD meta-analysis: opportunities and challenges

Professor Richard Riley

Clinical prediction models predict disease presence and outcome occurrence in individuals [1], thereby informing diagnosis and prognosis. After a model is developed, its robustness and generalisability should be verified in one or more external validation studies. External validation uses new... Read more

Clinical prediction models predict disease presence and outcome occurrence in individuals [1], thereby informing diagnosis and prognosis. After a model is developed, its robustness and generalisability should be verified in one or more external validation studies. External validation uses new participant-level data, external to that used for model development, to examine whether the model’s predictions are reliable in individuals from potential population(s) for clinical use. Unfortunately, there are relatively few external validation studies, which is often attributed to the lack of external data available immediately after model development. However, increasingly researchers have access to ‘big’ data as evident by meta-analyses using individual participant data (IPD) from multiple studies [2], and by analyses of databases and registry data containing e-health records for thousands or even millions of patients from multiple practices, hospitals, or countries. In this presentation, we illustrate why big data heralds an exciting opportunity to improve the uptake of external validation research [3]. In particular, it allows a model’s predictive performance (e.g. in terms of discrimination and calibration) and clinical utility (e.g. in terms of net-benefit) to be evaluated across different clinical settings, populations, and subgroups of intended use. Using real examples (including new evaluation of QRISK2) we show that simply reporting a model’s overall performance (averaged across all clusters and individuals) can mask deficiencies. Rather, meta-analysis techniques such as funnel plots and prediction intervals can be used to summarise the distribution of performance, and to identify settings in which a model is not adequate or requires recalibration (updating) before implementation. 1. Steyerberg EW, Moons KG, van der Windt DA, Hayden JA, Perel P, Schroter S, Riley RD, Hemingway H, Altman DG. Prognosis Research Strategy (PROGRESS) 3: prognostic model research. PLoS Med 2013; 10: e1001381. 2. Debray TPA, Riley RD, Rovers MM, Reitsma JB, Moons KGM. Individual Participant Data (IPD) Meta-analyses of Diagnostic and Prognostic Modeling Studies: Guidance on Their Use. PLoS Med 2015; 12: e1001886. 3. Riley RD, Ensor J, Snell KI, Debray TP, Altman DG, Moons KG, Collins GS. External validation of clinical prediction models using big datasets from e-health records or IPD meta-analysis: opportunities and challenges. BMJ 2016; 353: i3140. Richard Riley is a Professor of Biostatistics at Keele University, which he joined in October 2014. He previously held posts at the Universities of Birmingham, Liverpool and Leicester. His current role focuses on statistical and methodological research for prognosis and meta-analysis, whilst supporting clinical projects in these areas. He is also a Statistics Editor for the BMJ and a co-convenor of the Cochrane Prognosis Methods Group; co-leads a summer school in Prognosis Research Methods; and leads a number of statistical training courses for risk prediction and meta-analysis.

Audience: Members of the University only

Organisers: Dr Maria Vazquez-Montes

Tue 26 Sep 2017 from 12:00 to 13:00

Peter Medawar Building Seminars

Medawar Building, Level 30 Seminar Room, off South Parks Road OX1 3SY

The role of non-coding RNAs in viral infection and the immunometabolic response

John Pezacki

This lecture will cover noncoding RNAs, specifically microRNAs (miRNAs) discovered to be oppositely regulated by the hepatitis C virus and the immunometabolic response to viral infection. Efforts to develop new therapeutic strategies based on these discoveries will also be discussed.

This lecture will cover noncoding RNAs, specifically microRNAs (miRNAs) discovered to be oppositely regulated by the hepatitis C virus and the immunometabolic response to viral infection. Efforts to develop new therapeutic strategies based on these discoveries will also be discussed.

Audience: Members of the University only

Organisers: Prof Lynn Dustin

Please arrive 5 minutes early for building access

Tue 26 Sep 2017 from 13:00 to 14:00

Molecular Haematology Unit, WIMM

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

Mechanotransduction in physiology and cardiovascular disease

Professor Ellie Tzima

Audience: Members of the University only

Organisers: Liz Rose

Wed 27 Sep 2017 from 13:30 to 14:30

MRC HIU Wednesday Seminar Series

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

Inflammation at the interface: dendritic cell coordination of Type 2 immunity

Prof. Andrew S. MacDonald

Audience: Members of the University only

Organisers: Anne Farmer

Wed 27 Sep 2017 from 14:00 to 15:00

BDI seminars

Big Data Institute, BDI LG Seminar Room 0, Old Road Campus OX3 7LF

BDI Seminar: Medical Research and Intellectual Property Rights / things to consider and things to avoid

Jonathan Sellors

This is an informal review of the role of intellectual property rights over the past few years in medical research, in particular: i) What intellectual property rights actually exist in clinical data and medical discoveries; ii) How have these rights been used and exploited: the virtuous and the not so virtuous; iii) Things to be careful about and things to avoid (other than lawyers generally).

This is an informal review of the role of intellectual property rights over the past few years in medical research, in particular: i) What intellectual property rights actually exist in clinical data and medical discoveries; ii) How have these rights been used and exploited: the virtuous and the not so virtuous; iii) Things to be careful about and things to avoid (other than lawyers generally).

Audience: Members of the University only

Organisers: Natasha Bowyer

Fri 29 Sep 2017 from 08:00 to 09:00

Surgical Grand Rounds

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

Establishing a Comprehensive Reconstructive Microsurgery Center at Chang Gung University Medical Center

Professor Fu-Chan Wei

Professor Fu-Chan Wei is one of the pioneers in plastic and reconstructive surgery as well as microsurgery. He heads the world’s busiest microsurgery unit that has performed in excess of 26,000 microsurgical procedures at the Chang Gung Memorial Hospital in Taiwan. His main contributions include:... Read more

Professor Fu-Chan Wei is one of the pioneers in plastic and reconstructive surgery as well as microsurgery. He heads the world’s busiest microsurgery unit that has performed in excess of 26,000 microsurgical procedures at the Chang Gung Memorial Hospital in Taiwan. His main contributions include: toe-to-hand transfer, the osteoseptocutaneous fibula flap as well as perforator and free style free flaps. Following his appointment as Chairman of the Department of Plastic and Reconstructive Surgery at Chang Gung Memorial Hospital in 1994, Professor became Vice Superintendent in 1997 and Chancellor of the College of Medicine at Chang Gung University in 2003. Under his leadership as Chief of the Department of Plastic and Reconstructive Surgery, Chang Gung developed into a world leading microsurgical center renowned for undertaking extensive and highly complex cases including the reconstruction of the head and neck region, facial palsy, brachial plexus, upper and lower extremities, breast and lymphedema, at a standard that is the envy of all units across the globe. Professor Wei is past President of the World Society for Reconstructive Microsurgery and has published 468 research papers, 114 book chapters and 18 books. In 2012, he was elected to the Academia Sinica in Taiwan. Among his accolades are the American Plastic Surgery Foundation Outstanding Achievement in Clinical Research Award and the Honorary Award from the American Association of Plastic Surgeons. In 2006, Professor Wei was named Top 20 Plastic Surgery Innovator of American Society of Plastic Surgeon Professor Wei remains clinically active and his current research interests are focused on developing hand and face vascular composite allotransplantation in Taiwan.

Audience: Members of the University only

Organisers: Tarryn Ching

Fri 29 Sep 2017 from 09:15 to 10:15

MRC HIU Friday Morning Lab Meetings

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

Structural and regulatory diversity shape HLA-C protein expression levels

Dr Gurman Kaur

Audience: Members of the University only

Organisers: Anne Farmer

Fri 29 Sep 2017 from 12:00 to 13:00

Kennedy Institute Seminars

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

Development of CpG Oligonucleotides for the Immunotherapy of Cancer

Robert L Coffman PhD

Prior to joining Dynavax in 2000, Dr Coffman was a founding member of the scientific staff of the DNAX Research Institute in Palo Alto, CA, USA. Dr Coffman has authored over 200 scientific publications, and is a member of the National Academy of Sciences and the American Academy of Microbiology. ... Read more

Prior to joining Dynavax in 2000, Dr Coffman was a founding member of the scientific staff of the DNAX Research Institute in Palo Alto, CA, USA. Dr Coffman has authored over 200 scientific publications, and is a member of the National Academy of Sciences and the American Academy of Microbiology. He has devoted over 25 years to discovery of the pathways of immune regulation by T cells and cytokines. Dr Coffman demonstrated that interleukin-4 and interferon-g were the principal cytokines regulating IgE production in allergic responses. In 1986, with colleague Dr Tim Mosmann, he defined the two principal subtypes of helper T cells, termed Th1 and Th2 cells, and demonstrated subsequently that all of the major features of allergic responses were co-ordinately regulated by the Th2 subset of T cells. Dr Coffman demonstrated that interleukin-4 mediated class switching to IgE by controlling rearrangement of immunoglobulin genes, and discovered the parallel mechanism for the regulation of IgA responses by transforming growth factor-b. Dr Coffman has defined mechanisms of T-cell regulation in asthma and infectious and parasitic diseases, and demonstrated the central role of regulatory CD4+ T cells in preventing inflammatory bowel disease. In his current position at Dynavax, Dr Coffman is developing agonists and antagonists for Toll-like receptors, key recognition receptors in innate immunity. These compounds show promise as novel therapeutic agents for the treatment of allergic, infectious, and autoimmune diseases.

Audience: Members of the University only