Seminars

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Mon 18 Nov 2019 from 12:00 to 13:00

Kennedy Institute Seminars

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

Sugar is not just for tea! Sweet tasting fibroblasts in inflammatory Rheumatoid Arthritis.

Dr Miguel Pineda

In healthy joints, Synovial Fibroblasts (SFs) provide the required stromal support, but are recognized to adopt a pathological role in rheumatoid arthritis, delivering region-specific signals to infiltrating cells that perpetuate inflammation. Interventions targeting SFs would improve current... Read more

In healthy joints, Synovial Fibroblasts (SFs) provide the required stromal support, but are recognized to adopt a pathological role in rheumatoid arthritis, delivering region-specific signals to infiltrating cells that perpetuate inflammation. Interventions targeting SFs would improve current systemic therapies by directly modifying disease progression. Unfortunately, our collective understanding of stromal immunology has not been translated to the clinic and new strategies are needed to find novel therapeutic targets. The vast, and yet unexploited amount of information contained in cell glycomes could offer such molecular targets, as glycans - or carbohydrates - are being increasingly recognized as fundamental regulators of cellular interactions between stromal and immune cells. Our results show that transformation of SFs into pro-inflammatory cells in arthritis is associated with glycan remodelling in response to pro-inflammatory mediators, a process that involves regulation of terminal sialylation. Implications for changes in glycosylation pathways in disease progression and remission will be discussed.

Audience: Public

Organisers: Jennifer Pope

Mon 18 Nov 2019 from 12:30 to 13:30

Population Health Seminars

Big Data Institute, Old Road Campus OX3 7LF

HERC Seminar: A personalized screening strategy for diabetic retinopathy: a cost-effectiveness perspective

Talitha Feenstra

We examined the cost-effectiveness of three screening strategies for diabetic retinopathy (DR); using a personalized model, annual screening, and the most recent Dutch guideline. The Dutch guideline has variable intervals based on pre-existing retinopathy scores from immediate referring for... Read more

We examined the cost-effectiveness of three screening strategies for diabetic retinopathy (DR); using a personalized model, annual screening, and the most recent Dutch guideline. The Dutch guideline has variable intervals based on pre-existing retinopathy scores from immediate referring for treatment up to 3 years. For each individual, DR screening intervals were determined for personalized screening using different STR risk margins. Observational data (1998-2017) from the Hoorn Diabetes Care System cohort of people with type 2 diabetes, were used (N=5,514). In order to evaluate the performance of the model, the actual time to develop STR in the cohort was used and for missing values of this variable, two alternative scenarios were assumed: slow and fast STR progression. Missed cases, the outcome of each strategy, were determined by comparing model based screening intervals to observed time to develop STR. Costs were calculated based on screening and travel costs. Finally, outcomes and costs were compared for the different screening strategies. Comparing personalized screening with annual screening resulted in 11.0% and 11.6% more missed cases with €10.4 and €8.3 less cost per patient for slow and fast STR progression assumptions, respectively. The personalized screening strategy performed better in terms of diagnosing STR cases and it had 7.1% and 9.1% less missed cases compared to Dutch guideline screening strategy. While for a slow STR progression assumption, personalized screening strategy reduced costs with €0.2 per patient, assuming fast STR progression personalized screening was €1.9 per patient more expensive than current Dutch guideline strategy. Missing cases would be found at a later time, with a median delay of 19 months for personalized screeening, and 12 months for the Dutch guideline strategy. Personalized retinopathy screening is more cost-effective than the Dutch guideline screening strategy. Although the personalized screening strategy was less effective than annual screening, the number of late diagnosed STR patients is low and the saving is considerable. With around 1,000,000 people with type 2 diabetes in the Netherlands, implementing this personalized model could save 8.5 to 10.6 million euros

Audience: Members of the University only

Organisers: Graham Bagley

Mon 18 Nov 2019 from 13:00 to 14:00

WIMM MONDAY SEMINARS

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

Using single cell RNA sequencing to investigate mechanisms of liver fibrosis and regeneration

Prof Neil Henderson

Audience: Members of the University only

Organisers: Liz Cloke

Mon 18 Nov 2019 from 16:00 to 17:00

WIMM Occasional Seminars

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

“Clonal hematopoiesis in human aging and disease”.

Siddhartha Jaiswal

Audience: Members of the University only

Organisers: Emma Butterfield

Tue 19 Nov 2019 from 10:00 to 11:00

BDI seminars

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

BDI Seminar - Will big data deliver new drug targets?

Dr Andrew Leach, Dr Rob Finn

An ever-increasing volume and complexity of data is now available within the life sciences, much of it potentially relevant to drug discovery. Methods to integrate, analyse and visualise such data are key to making effective decisions in the discovery and development of new medicines. The European... Read more

An ever-increasing volume and complexity of data is now available within the life sciences, much of it potentially relevant to drug discovery. Methods to integrate, analyse and visualise such data are key to making effective decisions in the discovery and development of new medicines. The European Bioinformatics Institute, based on the Wellcome Genome Campus in Hinxton, develops and delivers many of these data resources and tools to the scientific community, freely available and without restriction on use. In this talk, we will describe some of the data resources and workflows that can be used to answer practical questions in drug discovery, with a particular focus on target selection. The Open Targets (OT) collaboration is an important project in this context; the OT informatics platform integrates data relevant to targets and diseases from multiple resources and provides an easy-to-use interface to help users explore and process the data. Complementing the target-disease evidence relationships within OT is a target tractability platform, which helps users assess the "do-ability' of a target, for both small molecule and antibody modalities. We will also describe our work to explore the composition of the human microbiome, and its potential role in health and disease. As the number and size of the datasets from the human gut microbiome have increased, a more elaborate picture is beginning to form about the complexity of the microbiota. The relevance of these new discoveries, the current limitations and the potential for novel drug discovery will be outlined.

Audience: Members of the University only

Tue 19 Nov 2019 from 13:00 to 14:00

Molecular Haematology Unit, WIMM

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

Recent progress towards understanding the molecular mechanism of X chromosome inactivation

Professor Neil Brockdorff

Audience: Members of the University only

Organisers: Liz Rose

Tue 19 Nov 2019 from 13:00 to 14:00

Population Health Seminars

Big Data Institute, Seminar rooms, Old Road Campus OX3 7LF

Professor Tyler VanderWeele

Professor Tyler Vanderweele

Audience: Members of the University only

Organisers: Graham Bagley

Tue 19 Nov 2019 from 17:00 to 18:00

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

Panel: (Inter)nationalising the antibiotic pipeline: public options for antibiotic R&D

Dr Andrew Singer, Dr Claas Kirchhelle, Dr Adam Roberts

The Oxford Martin School, Liverpool School of Tropical Medicine and the UK Centre for Ecology & Hydrology invite you to a panel discussion during World Antibiotic Awareness Week on new solutions to the stalled antibiotic research and development (R&D) pipeline. This event is organised by the... Read more

The Oxford Martin School, Liverpool School of Tropical Medicine and the UK Centre for Ecology & Hydrology invite you to a panel discussion during World Antibiotic Awareness Week on new solutions to the stalled antibiotic research and development (R&D) pipeline. This event is organised by the Oxford Martin Programme on Collective Responsibility for Infectious Disease. Over the past three decades, the rapid rise of antimicrobial resistance and the lack of new antibiotics have created a perfect storm for global health and food systems. Antibiotic effectiveness is an endangered global common resource in urgent need of new solutions to protect existing drugs and to develop novel compounds. This event brings together experts from the medical, natural, and social sciences to discuss both the status quo and new approaches to global drug development and stewardship. In addition to the current focus on using public money to reinvigorate private drug development, panellists will discuss alternatives such as a public buyout of existing patents and a long-term (inter)nationalisation of antibiotic development as well as solutions for the dilemma of curbing AMR and enhancing global access to effective antimicrobials. 5:00 - 5:15pm: (Inter)nationalising the antibiotic pipeline: public options for antibiotic R&D Dr Andrew Singer (microbiologist, UK Centre for Ecology & Hydrology), Dr Claas Kirchhelle (historian, Oxford Martin School), Dr Adam Roberts (microbiologist, Liverpool School of Tropical Medicine) will introduce their new publication on public options for antibiotic development in Lancet Infectious Diseases. 5:15 - 6:00pm: Panel discussion with questions from the audience An expert panel will discuss the economic, social, and microbiological dimensions of drug development, stewardship, and infection control in the 20th and 21st centuries: Ellen Silbergeld (environmental and public health, Johns Hopkins University), Koen Pouwels (modeller and economist, University Oxford), Viviane Quirke (historian, Oxford Brookes University), Javier Lezaun (social scientist, Institute for Science, Innovation, and Society, Oxford) Nicola Elvis (microbiologist, Public Health England). More information can be found here: https://www.oxfordmartin.ox.ac.uk/events/antibiotics-panel/

Booking Required

Audience: Public

Wed 20 Nov 2019 from 11:30 to 12:30

WHG Seminars

Old Road Campus Research Building, Ludwig Seminar Room, Headington OX3 7DQ

Global tumor transcriptional activity reveals aggressiveness across multiple cancers

Dr Wenyi Wang

The ability to determine whether a cancer is indolent or aggressive is highly desirable for clinical decision making. Current standard-of-care uses histological and pathological stages. Biologists have identified proliferative markers such as Ki67 to have prognostic significance across multiple... Read more

The ability to determine whether a cancer is indolent or aggressive is highly desirable for clinical decision making. Current standard-of-care uses histological and pathological stages. Biologists have identified proliferative markers such as Ki67 to have prognostic significance across multiple solid tumors. Interestingly, the canonical oncogene MYC has been shown to increase the global gene expression level in tumor cells. However, the total number of mRNA molecules is not directly measurable, either in bulk or single-cell RNA sequencing data. Here, using a joint deconvolution model with matching bulk RNA and DNA sequencing data, we propose a novel metric, transcriptional activity score (TAS), to measure the ratio of global gene expression levels in tumor cells to that in surrounding non-tumor cells. Using data from The Cancer Genome Atlas and from the International Cancer Genome Consortium, we found that higher TAS was associated with more aggressive behavior, as defined by survival outcomes, pathologic correlates, and genomic features known to associate with aggressive behavior (e.g. genomic instability, whole genome doubling) in multiple cancer types. We further applied TAS to annotate somatic mutational events for their impact on global rather than local expression changes. In this talk, I will present the development of our transcriptome deconvolution model, DeMixT, and the subsequent development of TAS and our biological findings using the consortial datasets. In summary, we have developed a new summary metric using sequencing data from patient tumor samples, to compute, in vivo and using deconvolution, the relative global gene expression level of tumor cells. TAS may serve as a tractable phenotype to help elucidate the biology that underlies metastasis, prognosis and response to treatment in cancer.

Audience: Members of the University only

Organisers: Isabel Schmidt

Wed 20 Nov 2019 from 13:00 to 14:00

OCDEM Wednesday Seminar Series

Programming of cardio-metabolic disease by maternal over-nutrition: a developing crisis

Professor Susan Ozanne

Audience: Members of the University only

Wed 20 Nov 2019 from 13:00 to 14:00

Big Data Institute, BDI/NDPH Building Seminar Rooms, Old Road Campus OX3 7LF

Research Ethics for Researchers in the Medical Sciences Division

Dr Helen Barnby-Porritt

The aims of this session are to understand: • what Research Integrity means • why Oxford has an ethics review system for research involving human participants, human tissue and/or personal data • what research is reviewed by the Medical Sciences Interdivisional Research Ethics Committee (MS... Read more

The aims of this session are to understand: • what Research Integrity means • why Oxford has an ethics review system for research involving human participants, human tissue and/or personal data • what research is reviewed by the Medical Sciences Interdivisional Research Ethics Committee (MS IDREC) versus NHS Ethics Committees • where, and how, to apply for ethical approval • how to protect personal data obtained in research

Audience: Members of the University only

Organisers: Graham Bagley

Wed 20 Nov 2019 from 13:00 to 14:00

WHG Seminars

Wellcome Trust Centre for Human Genetics, Room B, Headington OX3 7BN

How can ethics add value for pathogen sequencing in research, clinical practice and public health?

Dr Stephanie Johnson

Genetic information derived from pathogens is an increasingly essential input for infectious disease control, public health and research. While the technical developments of sequencing technology are being implemented at a rapid pace, the non-technical aspects of implementing this technology are... Read more

Genetic information derived from pathogens is an increasingly essential input for infectious disease control, public health and research. While the technical developments of sequencing technology are being implemented at a rapid pace, the non-technical aspects of implementing this technology are still being broadly discussed. The successful implementation of this rapidly developing technology will, for example, require sharing of samples and metadata, interdisciplinary global collaborative partnerships, and will need to offer useful evidence for public health decision-making. Importantly, appropriately addressing these challenges will require the systematic identification, and analysis of a number of complex ethical, legal and social issues. A number of factors will contribute to the types of ethical issues that arise in different instances. These are likely to include characteristics of the disease, the environmental, political and geographical context, existing laws and policies, public attitudes, and cultural differences. This talk will identify the emerging ethical challenges; assess the gaps in ethical frameworks or thinking, and consider how ethics can help to solve practical challenges.

Audience: Members of the University only

Organisers: Isabel Schmidt

Wed 20 Nov 2019 from 14:30 to 15:30

MRC HIU Wednesday Seminar Series

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

Overcoming constraints on adaptive immunity to HBV

Professor Mala Maini

Audience: Members of the University only

Organisers: Anne Farmer

Wed 20 Nov 2019 from 14:30 to 15:30

The George Institute for Global Health UK Seminars

75 George Street (Hayes House), Seminar Room, 1st Floor, Hayes House. Lift and stair access, 75 George Street OX1 2BQ

The double burden of diabetes and global infection

Susanna Dunachie

77% of people with diabetes mellitus now live in low and middle-income countries (LMIC), and the incidence of diabetes is accelerating in poorer communities. The majority of people with diabetes are thought to have Type 2 diabetes mellitus (T2DM) although further research on diabetes subtypes in... Read more

77% of people with diabetes mellitus now live in low and middle-income countries (LMIC), and the incidence of diabetes is accelerating in poorer communities. The majority of people with diabetes are thought to have Type 2 diabetes mellitus (T2DM) although further research on diabetes subtypes in LMIC is needed. Diabetes increases susceptibility to infection and / or worsens outcomes for major global infections such as tuberculosis (TB), dengue, influenza and Gram-negative sepsis including Salmonella species and the neglected tropical disease melioidosis. Melioidosis is caused by the soil bacterium Burkholderia pseudomallei, has a 40% hospitalised case fatality rate in LMIC, and an estimated 89,000 global death toll. People with diabetes have a twelve-fold increased risk of melioidosis compared to non-diabetics, and up to two-thirds of melioidosis patients have T2DM. There is a large overlap between populations at risk of diabetes and those at risk of melioidosis, resulting in an estimated 280 million people with diabetes now living in melioidosis-endemic countries across the world. In addition, people with diabetes bear a disproportionate burden of drug-resistant infections from bacteria with antimicrobial resistance (AMR). This talk will give an overview of what is known about the epidemiology of diabetes and infection, and discuss potential mechanisms for the increased risk of infection, and in particular for the exquisite susceptibility of people with diabetes to melioidosis. International treatment guidelines for T2DM are based on research conducted in high-income countries focussed on preventing adverse cardiovascular outcomes and early death. There is a lack of evidence on which to base treatment guidelines for people living in LMIC, where there is an increased burden of infectious diseases. The literature to date on the impact of treatment on infection risk and outcomes will be discussed. Finally, the role of vaccination of people with diabetes will be discussed. It is noted that a public health vaccine for melioidosis would be targeted at people with diabetes in the first instance, as this group represents a well-defined and accessible population for evaluation of a melioidosis vaccine.

Audience: All welcome

Wed 20 Nov 2019 from 16:00 to 17:30

Ethox Centre and Wellcome Centre for Ethics and Humanities

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

WEH/Ethox Seminar - Archival Ethics from Below: The Case of the Uganda Cancer Institute's Records

Dr Marissa Mika

At the Uganda Cancer Institute, lines often blur between past and present, sickness and health, life and death. Founded in 1967 as a small chemotherapy clinical trials facility in Kampala, today the Institute’s 100+ beds serve a population catchment of over 40 million living in the Great Lakes... Read more

At the Uganda Cancer Institute, lines often blur between past and present, sickness and health, life and death. Founded in 1967 as a small chemotherapy clinical trials facility in Kampala, today the Institute’s 100+ beds serve a population catchment of over 40 million living in the Great Lakes region of Africa. The Institute houses the only continuous collection of patient records documenting cancer treatment and care on the African continent. As this Institute gets torn down and built back up, so too do longstanding practices of cancer research and care. And with all of these changes at the Institute, there are major questions about what to preserve, what to discard, and what to celebrate. And in particular, what should be “done” with the institutional records and patient records at this site? This talk considers the temporal, methodological, and ethical challenges of preserving patient records at the Uganda Cancer Institute.

Audience: Members of the University only

Wed 20 Nov 2019 from 18:00 to 19:00

Centre for Personalised Medicine Seminars

St Anne's College, Tsuzuki Lecture Theatre, Woodstock Road OX2 6HS

Can education be personalised using pupils’ genetic data?

Dr Tim Morris

The predictive power of polygenic scores for some traits now rivals that of more classical phenotypic measures, leading to suggestions that polygenic scores offer a potentially useful tool for genetically informed policy. However, it is not well understood how much information polygenic scores... Read more

The predictive power of polygenic scores for some traits now rivals that of more classical phenotypic measures, leading to suggestions that polygenic scores offer a potentially useful tool for genetically informed policy. However, it is not well understood how much information polygenic scores convey for complex social traits such as education over and above phenotypic data that are available or easily measured. Using data from a UK cohort study we investigate the accuracy with which polygenic scores for education predict pupil’s realised attainment. We test their use as standalone predictors and conditional on phenotypic data that is available to or could be easily and cheaply collected by schools. In our sample, children’s polygenic scores predicted their educational outcomes almost as well as parent’s socioeconomic position or education. There was high overlap between the polygenic score and attainment distributions though, leading to weak predictive accuracy at the individual level. Conditional on prior attainment, polygenic scores were not predictive of later attainment. Our results suggest that while polygenic scores are informative for identifying group level differences in education, they currently have very limited use in predicting how well an individual will perform

Booking Required

Audience: Public

Organisers: Catherine Lidbetter

There will be a drinks reception after Tim's talk. All welcome.

Thu 21 Nov 2019 from 13:00 to 14:00

Medical Grand Rounds

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

Tropical Medicine Day

Dr Bernadette Young, Dr David Bonsall

Tropical Medicine: "You don't see that everyday", Dr Bernadette Young -- Tropical Medicine: "A lesson to Lyssa’n to: Prevention is Hobson's choice", Dr David Bonsall -- Chair: Prof Richard Cornall

Tropical Medicine: "You don't see that everyday", Dr Bernadette Young -- Tropical Medicine: "A lesson to Lyssa’n to: Prevention is Hobson's choice", Dr David Bonsall -- Chair: Prof Richard Cornall

Audience: Members of the University and NHS clinical staff.

Thu 21 Nov 2019 from 13:30 to 14:30

WIMM Occasional Seminars

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

VIVA - The regulation of zeta-globin

Dr. Andrew King

Audience: Members of the University only

Organisers: Liz Rose

Thu 21 Nov 2019 from 13:30 to 14:30

ARUK Oxford Drug Discovery Institute Seminar Series

NDM Building, Seminar room, Headington OX3 7FZ

More than Bystanders in Dementia—Understanding What Microglia Do

Dr Soyon Hong

Genome-wide association studies implicate microglia in Alzheimer’s disease (AD) pathogenesis, but how microglia contribute to cognitive decline in AD is unclear. Emerging research suggest microglia, the resident macrophages of the central nervous system, to be active participants in brain... Read more

Genome-wide association studies implicate microglia in Alzheimer’s disease (AD) pathogenesis, but how microglia contribute to cognitive decline in AD is unclear. Emerging research suggest microglia, the resident macrophages of the central nervous system, to be active participants in brain wiring. One mechanism by which microglia help eliminate synapses is through the classical complement pathway (C1q, CR3/C3). Data from multiple laboratories collectively suggest that there may be an aberrant reactivation of the complement-dependent pruning pathway in multiple models of neurologic diseases including AD. These data altogether suggest that microglia participate in synaptic pathology. However, how and which synapses are targeted are unknown. Furthermore, whether microglia directly impair synaptic function is unknown. Mechanistic insight into local signals that regulate neuroglia interactions will be key to developing potential therapeutic avenues to target in disease.

Audience: Members of the University only

Organisers: Kate Humphrey

Thu 21 Nov 2019 from 16:00 to 17:00

The Haldane Lecture Series

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

A hundred years on: 21st Century Insights into Human Oxygen Homeostasis

Peter J Ratcliffe

In 1911, work by Haldane, Fitzgerald and colleagues revealed the extraordinary sensitivity of blood haemoglobin levels to reduced atmospheric oxygen levels, a finding that introduced the physiological concept of an oxygen sensor. This lecture will outline advances in the molecular understanding of... Read more

In 1911, work by Haldane, Fitzgerald and colleagues revealed the extraordinary sensitivity of blood haemoglobin levels to reduced atmospheric oxygen levels, a finding that introduced the physiological concept of an oxygen sensor. This lecture will outline advances in the molecular understanding of oxygen sensing mechanisms, including the remarkable finding that all eukaryotic kingdoms use enzymatic protein oxidations coupled to proteostasis to signal oxygen levels in their cells. The physiological implications of these advances will be discussed, together with the opportunities and challenges raised in the therapeutic modulation of human oxygen sensing systems.

Audience: Members of the University only

Organisers: Professor David Paterson

Please note the lecture theatre capacity is restricted to 190 and seating is first come first served (Oxford University members only).

Fri 22 Nov 2019 from 08:00 to 09:00

Surgical Grand Rounds

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

Surgical Grand Rounds - Emergency

Dr Alex Novak

Audience: Members of the University only

Organisers: Tarryn Ching

Fri 22 Nov 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

Epigenetic regulation governs the differential response of cancer and T-cells to arginine starvation

Dr Nicholas Crump

Audience: Members of the University only

Organisers: Anne Farmer

Fri 22 Nov 2019 from 13:00 to 14:00

DPAG Head of Department Seminar Series

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

Architectural principles in central mammalian synapses

Prof. Dr. Christian Rosenmund

Synapses transduce action potentials into neurotransmitter release with extraordinary efficiency and temporal precision. To execute this function, it is imperative that the Ca2+ trigger signal is rapid and fast to efficiently activate the synaptic vesicle fusion machinery. Mechanistic analysis... Read more

Synapses transduce action potentials into neurotransmitter release with extraordinary efficiency and temporal precision. To execute this function, it is imperative that the Ca2+ trigger signal is rapid and fast to efficiently activate the synaptic vesicle fusion machinery. Mechanistic analysis revealed that both efficient fusion and efficient Ca2+ secretion coupling depends on closing the distances as much as possible between membranes and between Ca2+ channels and release machinery. Also, postsynaptic neurotransmitter receptors need to be close to sites of vesicle fusion to maximize postsynaptic responses. While most molecular players of synaptic function are known, whether and how they are spatially arranged are still poorly understood. I will present electron microscopy compatible live labelling approaches for pre- and postsynaptic players and analyzed their intrinsic position in the synapse in relationship to synaptic vesicle docking and fusion function. We demonstrate physical alignment of synaptic vesicles, Ca2+ channels and postsynaptic AMPA receptors and fusion sites. Moreover, we show that forced transsynaptic coupling of Ca2+ channel subunits with postsynaptic AMPA receptors are sufficient in rescuing loss of synaptic organization and function upon loss of RIM/RBP, arguing that the core executors of synaptic transmission can also act as organizer of the synaptic apparatus.

Audience: Members of the University only

Organisers: Professor Zoltan Molnar

Fri 22 Nov 2019 from 13:00 to 14:00

WIMM Occasional Seminars

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

“Ontogeny of hematopoiesis: making blood before a blood stem cell”

James Palis, M.D

Audience: Members of the University only

Organisers: Liz Rose

Mon 25 Nov 2019 from 11:00 to 12:00

Department of Oncology

Old Road Campus Research Building, 00.71a, b and c, Headington OX3 7DQ

Mon 25 Nov 2019 from 12:00 to 13:00

Kennedy Institute Seminars

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

‘A new paradigm for cartilage lubrication: towards development of novel therapies for osteoarthritis’

Professor Jacob Klein

The articular cartilage coating the major mammalian joints, such as hips or knees, presents the most efficiently lubricated surfaces known in nature. When this lubrication breaks down, however, the result can be degradation of the articular cartilage, and onset of osteoarthritis (OA). In recent... Read more

The articular cartilage coating the major mammalian joints, such as hips or knees, presents the most efficiently lubricated surfaces known in nature. When this lubrication breaks down, however, the result can be degradation of the articular cartilage, and onset of osteoarthritis (OA). In recent years we have elucidated the molecular origins of the remarkable reduction in friction at the cartilage surface. Our results indicate that it is due to boundary layers in which several components act synergistically, exposing lipids at the slip plane, and I describe how this understanding may lead to novel approaches to alleviate OA.

Audience: Public

Organisers: Jennifer Pope

Mon 25 Nov 2019 from 13:00 to 14:00

WIMM MONDAY SEMINARS

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

Using genetic association to understand human biology

Professor Gil McVean

Patterns of genetic association have revealed much about the biology underlying human traits and complex diseases. But how can we use such information systematically to learn about the processes - at molecular, cellular and tissue levels - that modulate risk? I will discuss some challenges,... Read more

Patterns of genetic association have revealed much about the biology underlying human traits and complex diseases. But how can we use such information systematically to learn about the processes - at molecular, cellular and tissue levels - that modulate risk? I will discuss some challenges, approaches, and solutions to the problems of integrating and interpreting data on such a vast scale. And how such information can be applied to diverse problems ranging from therapeutic target identification to quantifying individual risk.

Audience: Members of the University only

Organisers: Liz Cloke

Mon 25 Nov 2019 from 15:00 to 16:00

BDI seminars

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

Phenome@BDI Seminar

Xilin Jiang, Luca Ferretti

1) “How genetic risk for common disease changes with age” - Xilin Jiang - DPhil student, working with Professor Gil McVean and Professor Chris Holmes. Genetics risk scores have great potential for disease prediction. However, most methods for estimating genetic risk assume that the effect is... Read more

1) “How genetic risk for common disease changes with age” - Xilin Jiang - DPhil student, working with Professor Gil McVean and Professor Chris Holmes. Genetics risk scores have great potential for disease prediction. However, most methods for estimating genetic risk assume that the effect is constant over age. Here, we present a framework for estimating how genetic risk changes with age and demonstrate that for many common diseases there is both age-dependent heterogeneity in how genetic risk affects future disease and, for a subset of diseases, multiple components of risk with distinct longitudinal profiles. To analyse longitudinal patterns of genetic risk, we use the proportional hazards model to estimate genetics effect sizes within age groups, conditioning on survival (i.e. no mortality, censoring or disease). We show that this approach is needed to avoid biases that arise in naive GWAS approaches, which are affected by the depletion of risk alleles in unaffected individuals over time and changes in baseline risk. We apply this model to the UK Biobank dataset, analysing 30 ICD-10 disease codes with prevalence > 1% and at least 20 independent associated variants. We use a Bayesian clustering approach on summary statistics to estimate latent curves and their posterior distributions, using spline functions to encourage smoothness in risk profiles over age and permutation tests to assess the evidence for distinct groups of variants with different age-related profiles. We identify 7 diseases with evidence for age-specific heterogeneity, including heart disease, skin cancer and gall-bladder diseases, several of which show evidence for more than one curve. We discuss biological processes that can result in such age-specific risk, notably gene-environment interactions, and the implications of these results for genetic prediction of risk. 2) " Genotype-phenotype maps, fitness landscapes and higher-order epistasis in microorganisms "- Luca Ferretti- Fraser group In recent years, advances in experimental evolution of microorganisms has enabled exploration of the fine structure of local genotype-phenotype maps and especially of fitness landscapes, i.e. genotype-fitness maps. These landscapes have been experimentally probed to an unprecedented level, obtaining information on fitness effects and epistasis at a local scale. Unfortunately, the high-dimensional nature of gene- or genome-level maps hinders all efforts towards a systematic exploration of their global properties, which are key to understand evolution on longer time scales. Hence, it is key to understand how local measures can be used to assess global features of these maps. The theory of fitness landscapes suggests that the structure of epistatic interactions plays a crucial role in determining the global topography of the landscape. In this talk, we will give an overview of recent developments in relation to local measures and global properties of genotype-phenotype maps. For experimentally resolved landscapes, several global properties can be predicted from local measures of epistasis. However, it is still unclear which features of long-term evolutionary dynamics could be predicted by experimental measures on small or sparse landscapes.

Audience: Members of the University only

Tue 26 Nov 2019 from 13:00 to 14:00

Molecular Haematology Unit, WIMM

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

Floor meeting - 2 groups will give an update on the research work in their laboratory

Dr Robert Beagrie, Dr Sarah Gooding

Audience: Members of the University only

Organisers: Liz Rose

Tue 26 Nov 2019 from 13:00 to 14:00

Richard Doll Seminars

Big Data Institute, Seminar rooms, Old Road Campus OX3 7LF

Richard Doll Seminar - Inhalable microplastics: a new cause for concern

Professor Frank Kelly

Audience: Members of the University only

Organisers: Graham Bagley

Tue 26 Nov 2019 from 13:00 to 14:00

SGC Seminars

NDM Building, TDI Basement Seminar Room, Headington OX3 7FZ

Host-directed therapies for tuberculosis targeting macrophage activation and stress resilience

Prof Igor Kramnik

Igor Kramnik obtained his PhD from the Central Institute for Tuberculosis Research of the Russian Academy of Sciences in Moscow, Russia. There he started his studies of lung-specific aspects of anti-tuberculosis immunity and discovered myeloid suppressor cells within pulmonary TB lesions. He... Read more

Igor Kramnik obtained his PhD from the Central Institute for Tuberculosis Research of the Russian Academy of Sciences in Moscow, Russia. There he started his studies of lung-specific aspects of anti-tuberculosis immunity and discovered myeloid suppressor cells within pulmonary TB lesions. He continued to study host immunity to mycobacteria at the Center for the Study of Host Resistance at McGill University in Montreal and the Albert Einstein College of Medicine in the Bronx, New York, with Emil Skamene and Barry Bloom, respectively. In 1999 he was recruited to the faculty at the Department of Immunology and Infectious Diseases at the Harvard School of Public Health in Boston. In 2009 he became an Investigator at the National Emerging Infectious Disease Laboratory and joined the Pulmonary Center at Boston University. During this period, he developed a mouse model of pulmonary TB that develop human-like necrotic TB granulomas and used this model to reveal the genetic control and mechanisms driving the necrotic pathology. His current research is focused on further dissecting the interplay of the host and bacterial factors leading to immunopathology in TB and the development of host-directed therapies to improve the outcomes of TB.

Audience: Members of the University only

Wed 27 Nov 2019 from 12:30 to 13:30

WHG Lunchtime Lab Talks

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

Grünewald & Hill Lunchtime Lab Talks

Lindsay Baker, Vojtech Prazak, Kathryn Auckland, Amanda Chong

Grünewald Group (Strubi) Speaker 1: Lindsay Baker Title: Towards Native Membrane Structural Biology Speaker 2: Vojta Prazak Title: Insights into Cellular Structural Biology by Electron Cryo-Tomography Hill Group (Immunology & Infectious Disease, Tropical Medicine & Global Health) Speaker 1:... Read more

Grünewald Group (Strubi) Speaker 1: Lindsay Baker Title: Towards Native Membrane Structural Biology Speaker 2: Vojta Prazak Title: Insights into Cellular Structural Biology by Electron Cryo-Tomography Hill Group (Immunology & Infectious Disease, Tropical Medicine & Global Health) Speaker 1: Kathryn Auckland Title: Genetic susceptibility to Rheumatic Heart Disease Speaker 2: Amanda Chong Title: Infection and Inflammation in UK Biobank

Audience: Members of the University only

Organisers: Isabel Schmidt

Wed 27 Nov 2019 from 14:30 to 15:30

The George Institute for Global Health UK Seminars

75 George Street (Hayes House), Seminar Room, 1st Floor, Hayes House. Lift and stair access, 75 George Street OX1 2BQ

Healthy and sustainable foods and diets (screening)

Professor Mike Rayner

Professor Rayner founded the Centre on Population Approaches for Non-Communicable Disease prevention in 1993 to focus on research into the promotion of healthier and more sustainable diets. The Centre is a World Health Organisation Collaborating Centre. In this seminar, he draws on his role with... Read more

Professor Rayner founded the Centre on Population Approaches for Non-Communicable Disease prevention in 1993 to focus on research into the promotion of healthier and more sustainable diets. The Centre is a World Health Organisation Collaborating Centre. In this seminar, he draws on his role with the Centre and as Chair of Sustain: the alliance for better food and farming in the UK, and as Chair of the Nutrition Expert Group for the European Heart Network to discuss healthy and sustainable foods and diets. Please note that this is a screening of a seminar delivered at The George Institute in Sydney in March 2019.

Audience: All welcome

Wed 27 Nov 2019 from 14:45 to 16:00

Nuffield Department of Primary Care Health Sciences - Department research seminars

St Luke's Chapel, Woodstock Road OX2 6GG

Unmaking and remaking: how I used and built theoretical frameworks throughout my DPhil

Caitlin Pilbeam

Caitlin is a Medical Anthropologist, completing her BA at Durham University before commencing her MSc and then DPhil at Oxford from 2015. Caitlin is part of the active teaching staff in both the PHC and Anthropology department, delivering on HERG, MSc EBM, and Medical Anthropology modules, in... Read more

Caitlin is a Medical Anthropologist, completing her BA at Durham University before commencing her MSc and then DPhil at Oxford from 2015. Caitlin is part of the active teaching staff in both the PHC and Anthropology department, delivering on HERG, MSc EBM, and Medical Anthropology modules, in addition to her role as visiting fellow at the University of Auckland. Caitlin’s DPhil research focussed on how people make ‘a life worth living’ whilst dying with chronic, degenerative heart failure at home towards the end of life. The talk will explore how conceptual distinctions and clarifications offered by phenomenology informed Caitlin's research methods, interview strategy, and fieldwork reflections. The theoretical lenses applied to analyse this work will be discussed, as well as how these lenses were further developed in conjunction with insights from data to build a theoretical framework of ‘unmaking and remaking’. This is a framework that can be more broadly applied to end of life research and practice.

Audience: Members of the University only

Thu 28 Nov 2019 from 13:00 to 14:00

Medical Grand Rounds

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

Dermatology / Radiology

Prof Fergus Gleeson

Dermatology: -- Radiology: Prof Fergus Gleeson -- Chair: Prof Hugh Watkins

Dermatology: -- Radiology: Prof Fergus Gleeson -- Chair: Prof Hugh Watkins

Audience: Members of the University and NHS clinical staff.

Thu 28 Nov 2019 from 13:00 to 14:00

WIMM Science Career Seminars

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

From nuclei to nuclei: transitioning from theoretical physics to biology

Dr Ed Morrissey

As part of the WIMM Science Career Seminar series, Dr. Ed Morrissey will tell us about his career in and out of academia and his transition from physics to biology.

As part of the WIMM Science Career Seminar series, Dr. Ed Morrissey will tell us about his career in and out of academia and his transition from physics to biology.

Audience: Members of the University only

Organisers: Dr Robert Beagrie

Thu 28 Nov 2019 from 14:00 to 15:00

Jenner Seminars

NDM Building, Seminar Room, Lower Ground Floor, Headington OX3 7FZ

Pathology-based approaches to underpin vaccine development for leishmaniasis

Prof Paul Kaye

Audience: Public

Organisers: Lisbeth Soederberg

Thu 28 Nov 2019 from 14:00 to 15:00

WIMM Occasional Seminars

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

Thu 28 Nov 2019 from 17:00 to 18:00

Population Health Seminars

Mathematical Institute, Lecture Theatre 1, Woodstock Road OX2 6GG

Thu 28 Nov 2019 from 17:15 to 19:00

Centre for Personalised Medicine Seminars

Mathematical Institute, L2, Woodstock Road OX2 6GG

Developing the NHS Genomic Medicine Service: Underpinning Precision Medicine

Professor Dame Sue Hill

Booking Required

Audience: Public

Organisers: Catherine Lidbetter

We are delighted to invite you to the Centre for Personalised Medicine’s Annual Lecture on Thursday 28th November 2019 in the Mathematical Institute (L2), Oxford. This year’s speaker is Professor Dame Sue Hill, Chief Scientific Officer for England, who will be delivering a lecture 'Developing the NHS Genomic Medicine Service: Underpinning Precision Medicine'. There will be a drinks reception at 17:15, followed by the lecture at 18:00.

Fri 29 Nov 2019 from 08:00 to 09:00

Surgical Grand Rounds

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

Facing the future with our eyes wide open. What does the future hold for (cardiac) surgery that will change the way we practice?

Mr George Krasopoulos

Mr George Krasopoulos has been a consultant cardiac surgeon since 2008 and joined the Oxford Heart Centre in July 2013. He holds the title of Hon. Professor in Cardiac Surgery and he is involved with the Universities of Oxford, Anglia Ruskin, Cumbria and Buckingham. In 2016, he joined the Liga... Read more

Mr George Krasopoulos has been a consultant cardiac surgeon since 2008 and joined the Oxford Heart Centre in July 2013. He holds the title of Hon. Professor in Cardiac Surgery and he is involved with the Universities of Oxford, Anglia Ruskin, Cumbria and Buckingham. In 2016, he joined the Liga College in Oxfordshire as a Non-Executive Director. His philosophy is based on providing surgical, medical and humanitarian services of the highest standards.

Audience: Members of the University only

Organisers: Tarryn Ching

Fri 29 Nov 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

Title TBC

McMichael Group

Audience: Members of the University only

Organisers: Anne Farmer

Fri 29 Nov 2019 from 13:00 to 14:00

DPAG Head of Department Seminar Series

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

Cell competition and the regulation of robustness of growth during early mouse development

Dr Tristan Rodriguez

During the early stages of mammalian embryonic differentiation a vast array of cellular changes take place, including a dramatic increase in the proliferation rate and a rewiring of the transcriptional, epigenetic, metabolic and signalling networks. The dimension of these changes and the... Read more

During the early stages of mammalian embryonic differentiation a vast array of cellular changes take place, including a dramatic increase in the proliferation rate and a rewiring of the transcriptional, epigenetic, metabolic and signalling networks. The dimension of these changes and the requirement for their timing to be carefully orchestrated implies that stringent quality control mechanisms must be in place to ensure the elimination of aberrant cells prior to the specification of the germline. Here I will discuss the work my laboratory has done to unravel the mechanism of elimination of non-lethally damaged cells during differentiation. I will present evidence to show that during embryonic differentiation, cells with mild forms of cellular damage, such as mis-patterning or karyotypical abnormalities are recognised as a less-fit by their neighbours that induce the elimination of these damaged cells. I will discuss how during this process the interplay of signalling and metabolic pathways governs the competitive interactions that ensue between cells with different fitness levels, as well as the implications of these interactions for the growth and patterning of the developing embryo.

Audience: Members of the University only

Organisers: Prof Shankar Srinivas