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Thu 11 Aug 2016 from 16:30 to 18:00

Experimental Medicine TGU Seminars

John Radcliffe Hospital - Main Building, Post Grad Centre Level 3, Headington OX3 9DU

Fri 12 Aug 2016 from 11:00 to 12:00

Strubi seminars

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

Structural insights into primary microRNA processing

Dr Jae-Sung Woo

MicroRNA (miRNA) maturation is initiated by Microprocessor composed of RNase III DROSHA and its cofactor DGCR8, whose fidelity is critical for generation of functional miRNAs. To understand how Microprocessor recognizes primary miRNAs (pri-miRNAs), we reconstitute human Microprocessor with purified... Read more

MicroRNA (miRNA) maturation is initiated by Microprocessor composed of RNase III DROSHA and its cofactor DGCR8, whose fidelity is critical for generation of functional miRNAs. To understand how Microprocessor recognizes primary miRNAs (pri-miRNAs), we reconstitute human Microprocessor with purified recombinant proteins. We find the ruler fuction of DROSHA and specify the accessary roles of DGCR8 domains by in vitro pri-miRNA processing assays. Furthermore, we solve the atomic structure of DROSHA in complex with the C-terminal helix of DGCR8. The overall structure of DROSHA is unexpectedly similar to that of DICER, suggesting that DROSHA may have evolved from an ancestral DICER. DROSHA however exhibits several unique features, such as a kinked conformation, a long DROSHA-specific insertion, and two zinc-finger motifs, which together contribute to substrate recognition and processing. In addition, we identify two DGCR8 binding sites on DROSHA which provide a key information to build the heterotrimeric Microprocessor model. These findings clarify long standing controversies over the Microprocessing mechanism and allow us to build a general model for pri-miRNA processing

Audience: Members of the University only

Organisers: Eleanor Martin

Wed 31 Aug 2016 from 11:00 to 12:00

Strubi seminars

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

Visualizing fast 3D dynamics of biological samples using light-sheet microscopy

Prof Pablo Loza

Light sheet fluorescence microscopy (LSFM) is a convenient tool for high resolution, 3D bio-imaging as it efficiently collects the generated fluorescence while at the same time minimizes photobleaching. Being based on an intrinsic plane illumination, it allows for a fast 2D imaging. Therefore, LSFM... Read more

Light sheet fluorescence microscopy (LSFM) is a convenient tool for high resolution, 3D bio-imaging as it efficiently collects the generated fluorescence while at the same time minimizes photobleaching. Being based on an intrinsic plane illumination, it allows for a fast 2D imaging. Therefore, LSFM has been put forward as an interesting candidate for fast volumetric (3D) imaging.Here I will present a LSFM microscope, combined with the use of wavefront coding (WFC) techniques, for fast volumetric imaging. WFC is used to extend the depth of field (DOF) of the collecting objective in a LSFM. This result in a system in which the light sheet can be scanned through the sample, which remains static, providing the LSFM with intrinsic 3D imaging capabilities. In addition, because of the extended DOF, the light sheet can be axially scanned at fast speeds. As only the light sheet is moved, fast 3D imaging can be achieved without the need of any sample or objective movement.

Audience: Members of the University only

Organisers: Agata Krupa

Wed 31 Aug 2016 from 14:00 to 15:00

WHG Seminars

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

Modelling rare genetic variation to investigate recent human history

Dr. Stephan Schiffels

By studying human genetic variation, recent studies have provided key insights into human history, including major migration events and population turnovers. However, for many historical questions, the events of interest involve populations that are very closely related with each other, which... Read more

By studying human genetic variation, recent studies have provided key insights into human history, including major migration events and population turnovers. However, for many historical questions, the events of interest involve populations that are very closely related with each other, which pushes many traditional methods to the limits of resolution. Here I will present a new method that we developed and recently published, rarecoal, which infers population history and identifies fine-scale genetic ancestry from rare variants. The method efficiently computes the joint site frequency spectrum of rare variants, by probabilistically modeling the coalescent tree of rare derived mutations under a population model with split times, branch population sizes and admixture edges. I will present two applications of rarecoal and related methods. In the first study, we analyse the genomes from 10 ancient English samples, excavated close to Cambridge and ranging from the late Iron Age to the middle Anglo-Saxon period. By analysing shared rare variants with hundreds of modern samples from Britain and Europe, we estimate that on average the contemporary East English population derives 38% of its ancestry from Anglo-Saxon migrations. Using rarecoal we find that the Anglo-Saxon samples are closely related to modern Dutch and Danish populations, while the Iron Age samples share ancestors with multiple Northern European populations. In the second study, we analyse hundreds of modern samples from Siberia and America and gain insights into the prehistory of Native Americans. In particular, we detect a gene flow event from Siberia into Athabaskan speaking Native Americans around 7,000 years ago, that is separate from first American ancestry and later immigrations of Eskimo-Aleuts. We also show that this Athabaskan-specific Siberian ancestry is closely related to the ancient Saqqaq individual, which confirms a previous hypothesis of Palaeo-Eskimo ancestry in Athabaskan speakers.

Audience: Members of the University only

Organisers: Professor Gil McVean