Other Seminars

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Wed 20 Feb 2019 from 12:00 to 13:00

CNCB Seminar Series

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

Cell-autonomous and Circuit-level Mechanisms of Circadian Timekeeping in Mammals: Genes, Neurons and Astrocytes

Michael Hastings

In mammals the cell-autonomous circadian clock pivots around a transcriptional/post-translational feedback loop. However, we remain largely ignorant of the critical molecular, cell biological, and circuit-level processes that determine the precision and robustness of circadian rhythms: what keeps... Read more

In mammals the cell-autonomous circadian clock pivots around a transcriptional/post-translational feedback loop. However, we remain largely ignorant of the critical molecular, cell biological, and circuit-level processes that determine the precision and robustness of circadian rhythms: what keeps them on track, and what determines their period, which varies by less than 5 minutes over 24 hours? The origin of this precision and robustness is the suprachiasmatic nucleus (SCN) of the basal hypothalamus, the principal circadian pacemaker of the brain. The SCN sits atop a circadian hierarchy that sustains and synchronises the innumerable cell-autonomous clocks of all major organs to solar time (and thereby to each other), by virtue of direct retinal innervation that entrains the transcriptional oscillator of the 20,000 or so component cells of the SCN. I shall describe real-time imaging approaches to monitor circadian cycles of gene expression and cellular function in the SCN, and intersectional genetic and pharmacological explorations of the cell-autonomous and circuit-level mechanisms of circadian timekeeping. A particular focus will be on “translational switching” approaches to controlling clock function and the surprising discovery of a central role for SCN astrocytes in controlling circadian behaviour.

Audience: Members of the University only

Organisers: Fiona Woods

Wed 20 Feb 2019 from 12:00 to 13:00

Peter Medawar Building Seminars

Medawar Building, Seminar room, South Parks Road, Oxford, OX1 3SY, off South Parks Road OX1 3SY

Historical and modern rabbit populations reveal parallel adaptation to myxoma virus across two continents

Dr Joel Alves

In the 1950s the myxoma virus was deliberately released into wild European rabbit populations in Australia and Europe. The subsequent pandemic decimated populations and resulted in a remarkable natural experiment, where rabbits in both continents rapidly evolved resistance to the virus. We... Read more

In the 1950s the myxoma virus was deliberately released into wild European rabbit populations in Australia and Europe. The subsequent pandemic decimated populations and resulted in a remarkable natural experiment, where rabbits in both continents rapidly evolved resistance to the virus. We investigated the genetic basis of this resistance by comparing the exomes of modern individuals with the exomes of historical rabbit specimens collected before the virus release. By replicating our analyses in Australia, France and the United Kingdom we found a strong pattern of parallel selection across the three countries, with the same genetic variants changing in frequency over the last 60 years. Notably, these occurred in genes involved in antiviral immunity and viral replication, and support a polygenic basis of resistance. We experimentally validated the functional role of these genes as viral modulators and showed that selection acting on three amino acids in an interferon protein increased its antiviral effect.

Audience: The scientific community

Organisers: Dr Proochista Ariana

Please arrive 5 minutes before the seminar begins to gain access to the building

Thu 21 Feb 2019 from 11:00 to 12:00

Ludwig Institute Seminar Series

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

Engineering the cellular microenvironment with functional and living materials

Professor Manuel Salmeron-Sanchez

Audience: Members of the University only

Organisers: Christina Woodward

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

Medical Grand Rounds

Respiratory / Gastroenterology

Dr Chris Turnbull, Professor Richard Hunt

Respiratory: "An unusual case of breathlessness", Dr Chris Turnbull -- Gastroenterology: "The long term safety of PPIs", Prof Richard Hunt, Emeritus Professor of Medicine at McMaster University -- Chair: Prof Chris Conlon

Respiratory: "An unusual case of breathlessness", Dr Chris Turnbull -- Gastroenterology: "The long term safety of PPIs", Prof Richard Hunt, Emeritus Professor of Medicine at McMaster University -- Chair: Prof Chris Conlon

Audience: Members of the University and NHS clinical staff.

Thu 21 Feb 2019 from 14:30 to 15:00

Experimental Medicine TGU Seminars

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

IL-23 signalling as a putative novel therapeutic target in human colorectal cancer

Dr Elizabeth Mann

Audience: Members of the University only

Organisers: Dr Carolina Arancibia

Thu 21 Feb 2019 from 15:00 to 15:30

Experimental Medicine TGU Seminars

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

Microbiota, Intestinal Inflammation and Arthritis - Lessons from a Novel Immunodeficiency.

Dr Dominik Aschenbrenner

Mendelian disorders can inform on key pathogenic mechanism in humans. The analysis of a human immunodeficiency disorder suggests a novel link between intestinal microbiota, epithelial barrier function and the immune system leading to intestinal inflammation and arthritis.

Mendelian disorders can inform on key pathogenic mechanism in humans. The analysis of a human immunodeficiency disorder suggests a novel link between intestinal microbiota, epithelial barrier function and the immune system leading to intestinal inflammation and arthritis.

Audience: Members of the University only

Organisers: Dr Carolina Arancibia

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

Surgical Grand Rounds

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

Latest surgical developments in ultra-radical surgery for the management of advanced ovarian cancer

Mr Hooman Soleymani majd

Audience: Members of the University only

Organisers: Tarryn Ching

Fri 22 Feb 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

Autophagy, hematopoietic stem cells, and amino acids

Dr Sandrine Obba

Audience: Members of the University only

Organisers: Anne Farmer

Fri 22 Feb 2019 from 15:30 to 16:30

Ludwig Institute Seminar Series

Old Road Campus Research Building, Ludwig seminar room, lower ground floor. , Headington OX3 7DQ

“Roles of Pol Epsilon in genetic and epigenetic stability”

Dr Roberto Bellelli

Audience: Members of the University only

Organisers: Alexandra Ward

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

Strubi seminars

Wellcome Trust Centre for Human Genetics, Meeting room A , Headington OX3 7BN

THE STRUCTURAL BASIS FOR RELEASE FACTOR ACTIVATION DURING TRANSLATION TERMINATION REVEALED BY TIME-RESOLVED CRYOGENIC ELECTRON MICROSCOPY

Dr Ziao Fu

When the mRNA translating ribosome encounters a stop codon in its aminoacyl site (A site), it recruits a class-1 release factor (RF) to induce hydrolysis of the ester bond between peptide chain and peptidyl-site (P-site) tRNA. This process, called termination of translation, is under strong... Read more

When the mRNA translating ribosome encounters a stop codon in its aminoacyl site (A site), it recruits a class-1 release factor (RF) to induce hydrolysis of the ester bond between peptide chain and peptidyl-site (P-site) tRNA. This process, called termination of translation, is under strong selection pressure for high speed and accuracy. Class-1 RFs (RF1, RF2 in bacteria, eRF1 in eukarya and aRF1 in archaea), have structural motifs that recognize stop codons in the decoding center (DC) and a universal GGQ motif for induction of ester bond hydrolysis in the peptidyl transfer center (PTC) 70 Å away from the DC. The finding that free RF2 is compact with only 20 Å between its codon reading and GGQ motifs came therefore as a surprise. Cryo-electron microscopy (cryo-EM) then showed that ribosome-bound RF1 and RF2 have extended structures, suggesting that bacterial RFs are compact when entering the ribosome and switch to the extended form in a stop signal-dependent manner. FRET, cryo-EM and X-ray crystallography, along with a rapid kinetics study suggesting a pre-termination conformational change on the millisecond time-scale of ribosome-bound RF1 and RF2, have lent indirect support to this proposal. However, direct experimental evidence for such a short-lived compact conformation on the native pathway to RF-dependent termination is missing due to its transient nature. Here we use time-resolved cryo-EM to visualize compact and extended forms of RF1 and RF2 at 3.5 and 4 Å resolution, respectively, in the codon-recognizing complex on the pathway to termination. About 25% of ribosomal complexes have RFs in the compact state at 24 ms reaction time after mixing RF and ribosomes, and within 60 ms virtually all ribosome-bound RFs are transformed to their extended forms.

Audience: Members of the University only

Organisers: Agata Krupa

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

Population Health Seminars

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

NDPH Seminar: Methods for handling missing data and adjusting for non-adherence in cluster-randomised trials

Dr Karla Diaz-Ordaz

Cluster randomised trials (CRTs) often face issues with missing data and treatment non-adherence. Guidelines such as CONSORT require that the numbers of clusters and individuals randomised, receiving treatment and analysed are reported, while newer guidelines go further (see for example the ICH 9... Read more

Cluster randomised trials (CRTs) often face issues with missing data and treatment non-adherence. Guidelines such as CONSORT require that the numbers of clusters and individuals randomised, receiving treatment and analysed are reported, while newer guidelines go further (see for example the ICH 9 addendum on estimands), suggesting that an adherence-adjusted estimand is reported alongside an intention-to-treat estimate. For both analyses, missing data in covariates and outcome need to be handled appropriately as failure to do so can introduce bias in treatment effect estimates, leading to invalid inferences. Multiple imputation has become a popular method to handle missing data, and instrumental variables methods can be used to obtain adherence-adjusted average treatment estimates (CACE). Both of these statistical techniques should reflect the hierarchical nature of CRT data. In this talk, I will present multilevel multiple imputation for continuous and binary data, and then present two approaches to obtain CACE for CRTs: (1) cluster-level analysis two-stage least square method, with inferences at the cluster level, and (2) mixture models with random effects for individual level CACE. I will illustrate these methods by re-analysing a CRT in UK primary health settings. The OPERA study trial, which studied the effect of a physiotherapist-led exercise intervention on depression and physical health in elderly residents of nursing home.

Audience: Members of the University only

Organisers: Graham Bagley

Mon 25 Feb 2019 from 11:30 to 12:30

Jenner Seminars

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

Development of Subunit Vaccines for Immunization Against Melioidosis

Prof Paul Brett

Audience: Public

Organisers: Lisbeth Soederberg

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

Kennedy Institute Seminars

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

New Insights into Mucosal Antibody Responses

Prof Andrea Cerutti

I will discuss our recent frindings on the ontogeny of secretory IgM responses, which emerge from gut plasma cells clonally affiliated to IgM+ memory B cells and some IgA+ memory B cells. I will also discuss new evidence on the biology of human IgA2 and IgD, two largely neglected mucosal... Read more

I will discuss our recent frindings on the ontogeny of secretory IgM responses, which emerge from gut plasma cells clonally affiliated to IgM+ memory B cells and some IgA+ memory B cells. I will also discuss new evidence on the biology of human IgA2 and IgD, two largely neglected mucosal antibodies. Differences between humans and mice will be emphasized. ---- Dr. Cerutti earned his MD in 1990 and specialized in Hematology in 1997 at Padua School of Medicine (Padua, Italy). He joined Weill Medical College of Cornell University (New York, NY) in 1996 as a Postdoctoral Fellow to do research in immunology. After finishing his post-doctoral studies, he climbed the academic ladder at Weill Medical College of Cornell University and was promoted to Assistant Professor in 2001 and Associate Professor in 2006. In 2009 he obtained Tenure and moved to Icahn School of Medicine at Mount Sinai (New York, NY) as a Professor. He also took an ICREA Professor position in IMIM (Barcelona, Spain). He published some 130 articles. The major focus of his research relates to the biology of systemic and mucosal B cells, including the regulation of antibody class switching and production. He serves as a reviewer for ERC, NIH, and other national agencies as well as all of the major immunology/biomedicine journals.

Audience: Members of the University only

Organisers: Laura Sánchez Lazo

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

WIMM MONDAY SEMINARS

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

Utilising the totality of mutagenesis for clinical purposes

Dr Serena Nik-Zainal

A cancer genome carries the historic mutagenic activity that has occurred throughout the development of a tumour1. While driver mutations were the main focus of cancer research for a long time, passenger mutational signatures - the imprints of DNA damage and DNA repair processes that have been... Read more

A cancer genome carries the historic mutagenic activity that has occurred throughout the development of a tumour1. While driver mutations were the main focus of cancer research for a long time, passenger mutational signatures - the imprints of DNA damage and DNA repair processes that have been operative during tumorigenesis - are also biologically informative1,2. In this lecture, I provide a synopsis of this concept, describe the insights that we have gained through combinations of computational analysis3,4 and experiments in cell-based systems5, and showcase how we have developed the concept into applications that we hope to translate into clinical utility in the near future3,4. I describe our efforts in a population-derived cohort as well as in individual patients, emphasizing the need for us to be more precise in analyses and interpretation in human cancer genomics. References: 1. Helleday T, Eshtad S, Nik-Zainal S. Mechanisms underlying mutational signatures in human cancers.Nat Rev Genet. 2014 Sep;15(9):585-98. doi: 10.1038/nrg3729. Epub 2014 Jul 1. Review. PubMed PMID: 24981601; PubMed Central PMCID: PMC6044419. 2. Alexandrov LB, Nik-Zainal S, et al. Signatures of mutational processes in human cancer. Nature. 2013 Aug 22;500(7463):415-21. doi: 10.1038/nature12477. Epub 2013 Aug 14. Erratum in: Nature. 2013 Oct 10;502(7470):258. Imielinsk, Marcin [corrected to Imielinski, Marcin]. PubMed PMID: 23945592; PubMed Central PMCID: PMC3776390. 3. Nik-Zainal S, Davies H, et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature. 2016 Jun 2;534(7605):47-54. doi: 10.1038/nature17676. Epub 2016 May 2. PubMed PMID: 27135926; PubMed Central PMCID: PMC4910866. 4. Davies H, Glodzik D, et al. and Nik-Zainal S. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat Med. 2017 Apr;23(4):517-525. doi: 10.1038/nm.4292. Epub 2017 Mar 13. PubMed PMID: 28288110; PubMed Central PMCID: PMC5833945. 5. Zou X, Owusu M, Harris R, Jackson SP, Loizou JI, Nik-Zainal S. Validating the concept of mutational signatures with isogenic cell models. Nat Commun. 2018 May 1;9(1):1744. doi: 10.1038/s41467-018-04052-8. PubMed PMID: 29717121; PubMed Central PMCID: PMC5931590.

Audience: Members of the University only

Organisers: Liz Cloke

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

Molecular Haematology Unit, WIMM

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

Spatial In Vivo Transcription Profiling with Single-Molecule Imaging

Dr Antti Lignell

Audience: Members of the University only

Organisers: Liz Rose

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

Population Health Seminars

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

Richard Doll Seminar: Progress in the management of breast cancer: Trials and tribulations

Professor David Dodwell

Audience: Members of the University only

Organisers: Graham Bagley

Tue 26 Feb 2019 from 14:30 to 15:30

Population Health Seminars

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

NPEU Seminar: Using qualitative research to shape, inform, and implement global guidelines in maternity care.

Prof. Soo Downe OBE

Audience: Members of the University only

Organisers: Graham Bagley

Wed 27 Feb 2019 from 12:00 to 13:00

Peter Medawar Building Seminars

Medawar Building, Seminar room, South Parks Road, Oxford, OX1 3SY, off South Parks Road OX1 3SY

Insights into the epidemiology of dengue and Zika from maps and models

Dr Oliver Brady

The mosquito-borne viral diseases of dengue and Zika are one of the fastest growing public health threats in the tropics. Mathematical models that describe how these diseases are spread are powerful tools for understanding their global emergence and their impact on affected populations. In this... Read more

The mosquito-borne viral diseases of dengue and Zika are one of the fastest growing public health threats in the tropics. Mathematical models that describe how these diseases are spread are powerful tools for understanding their global emergence and their impact on affected populations. In this talk I will show how spatial models fit to epidemiological data have allowed us to better understand ZIKV outbreaks, improve our understanding of the burden they impose in endemic areas and help us better plan for future spread.

Audience: The scientific community

Organisers: Dr Proochista Ariana

Please arrive 5 minutes before seminar begins to gain entry to the building

Wed 27 Feb 2019 from 13:30 to 14:30

MRC HIU Wednesday Seminar Series

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

Inferring epitope-specific T-cell receptor sequence motifs from immune repertoire sequencing data

Dr Mikhail Shugay

Audience: Members of the University only

Organisers: Anne Farmer

Thu 28 Feb 2019 from 11:00 to 12:00

Ludwig Institute Seminar Series

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

Analyzing T cells infiltrating tumours or other diseased tissues.

Professor Pierre Coulie

Audience: Members of the University only

Organisers: Alexandra Ward

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

Medical Grand Rounds

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

Palliative Care / Neurology

Dr Michele Hu, Dr Mary Miller

Palliative Care: "Does High Flow nasal Oxygen delay death?", Dr Mary Miller -- Neurology: "Prodromal Parkinson’s: what’s it all about?", Dr Michele Hu -- Chair: Prof Chris Conlon

Palliative Care: "Does High Flow nasal Oxygen delay death?", Dr Mary Miller -- Neurology: "Prodromal Parkinson’s: what’s it all about?", Dr Michele Hu -- Chair: Prof Chris Conlon

Audience: Members of the University and NHS clinical staff.

Thu 28 Feb 2019 from 13:30 to 14:30

Development & Cell Biology Theme Guest Speakers (DPAG)

Sherrington Building, Small Lecture Theatre, Second Floor, off Parks Road OX1 3PT

Functional dynamics of chromatin topology in human cardiogenesis and disease

Alessandro Bertero

Dr. Alessandro Bertero is a Senior Fellow in the Dept. of Pathology at the University of Washington in Seattle, USA. During his undergraduate studies he trained with the late Prof. Guido Tarone at the University of Turin in Italy, where he contributed to elucidate the Melusin-ERK1/2 signalling... Read more

Dr. Alessandro Bertero is a Senior Fellow in the Dept. of Pathology at the University of Washington in Seattle, USA. During his undergraduate studies he trained with the late Prof. Guido Tarone at the University of Turin in Italy, where he contributed to elucidate the Melusin-ERK1/2 signalling pathway in cardiac hypertrophy, and obtained a BSci (2009) and an MSci (2011). Having being awarded a British Heart Foundation Graduate Fellowship, he joined the laboratory of Prof. Ludovic Vallier at the University of Cambridge in the UK, where he obtained an MRes (2012) and a PhD (2016) by revealing the epigenetic and epitransciptional effects of TGFbeta-SMAD2/3 signalling during early differentiation of human pluripotent stem cells (hPSCs). In 2016, Dr. Bertero moved to the University of Washington for his postdoctoral training with Prof. Charles Murry. He was awarded an EMBO Long-Term Fellowship in 2017. His current focus is the study of three-dimensional chromatin organization, and of its importance both during human cardiogenesis and in the context of familiar cardiomyopathies. This work relies on stage-wise differentiation of hPSCs into cardiomyocytes, CRISPR/Cas9 gene editing, generation of 3D engineered heart tissues, analysis of cardiac physiology, and genomic approaches to probe nuclear architecture and function.

Audience: Members of the University only

Please contact Katie McNeil if you would like to meet with Alessandro during his visit

Thu 28 Feb 2019 from 16:00 to 18:00

Experimental Medicine TGU Seminars

John Radcliffe Hospital - Main Building, John Radcliffe Main Building, George Pickering Education Centre Level 3 Academic Centre, Room 2B, Headington OX3 9DU

Precision Medicine in Inflammatory Bowel Disease - Hype or Hope?

Professor Jack Satsangi

Audience: Members of the University only

Organisers: Professor Holm Uhlig