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Seminars

Institute of Cell Biology Seminar Series

 

January seminars will be held at 12.00 noon in the Michael Swann Lecture Theatre.

All other seminars will be held at 12.00 noon in Lecture Theatre 1, Daniel Rutherford Building.

Everyone is welcome to attend.

Semester Two: January - June 2015

 

Date

Speaker

Host

Venue

12th Jan 2015

Ana Pombo

Berlin Institute for Medical Systems Biology

Adrian Bird

Michael Swann

Main Lecture Theatre

19th Jan 2015

Luis Aragon

MRC Clinical Sciences Centre  ICL

Bill Earnshaw

Michael Swann

Main Lecture Theatre

26th Jan 2015

Anthony Bishopp

Plant Sciences, School of Biosciences, University of Nottingham

Justin Goodrich

Michael Swann

Main Lecture Theatre

2nd Feb

2015

Esben Lorentzen

Max Planck Institute of Biochemistry

JP Arulanandam

Michael Swann

Main Lecture Theatre

9th Feb 2015

Chris Smith

Department of Biochemistry, University of Cambridge

Jean Beggs

Daniel Rutherford

Lecture Theatre G27

16th Feb 2015

Titia Sixma

Netherlands Cancer Institute, Amsterdam

Atlanta Cook

Daniel Rutherford

Lecture Theatre G27

23rd Feb 2015

Paul Fraser

Plant Molecular Science, Centre for Systems & Synthetic Biology,

Royal Holloway College, University of London

Gary Loake

Daniel Rutherford

Lecture Theatre G27

2nd March 2015

Jordan Raff

Sir William Dunn School of Pathology, University of Oxford

Kevin Hardwick

Daniel Rutherford

Lecture Theatre G27

9th March 2015

Sheena Radford

The Astbury Centre for Structural Molecular Biology, University of Leeds

Paul Barlow

Daniel Rutherford

Lecture Theatre G27

16th March 2015

James Murray

Department of Life Sciences, Imperial College London

Atlanta Cook

Daniel Rutherford

Lecture Theatre G27

23rd March 2015

David Baulcombe

Department of Plant Sciences, University of Cambridge

David Finnegan

Daniel Rutherford

Lecture Theatre G27

30th March 2015

Saul Purton

Institute of Structural and Molecular Biology, University College London

Alistair McCormick

Daniel Rutherford

Lecture Theatre G27

6th April

2015

Easter Monday

 

 

13th April 2015

Genevieve Almouzni

Chromatin Dynamics Laboratory,  Nuclear Dynamics and Genome Plasticity Unit, UMR 218 CNRS / Institut Curie

Robin Allshire

Daniel Rutherford

Lecture Theatre G27

Tues 21st  April 2015

(one off)

Iva Tolic-Norrelykke

Max Planck Institute Of Molecular Cell Biology and Genetics

Teuta Pilitzota

Daniel Rutherford

Lecture Theatre G27

27th April 2015

Paul Knox

Plant Cell Wall Biology Lab, Centre for Plant Sciences, Faculty of Biological Sciences, University of Leeds

Naomi Nakayama

Daniel Rutherford

Lecture Theatre G27

Wed 6th May

2015

Jon Pines

Gurdon Institute, Cambridge

Hiro Ohkura

Daniel Rutherford

Lecture Theatre G27

Wed 13th May 2015

Cristina Cardoso

Technische Universität Darmstadt, Germany

Irina Stancheva

Daniel Rutherford

Lecture Theatre G27

Wed 20th May 2015

Shona Murphy

Sir William Dunn School of Pathology, University of Oxford

Jean Beggs

Daniel Rutherford

Lecture Theatre G27

Wed 27th May 2015

Tony Carr

University of Sussex

Kevin Hardwick

Daniel Rutherford

Lecture Theatre G27

8th June 2015

Ana Losada

Molecular Oncology Group, cnio (Centro Nacional de Investigaciones Oncológicas), Madrid

Irina Stancheva

Daniel Rutherford

Lecture Theatre G27

15th June 2015

David Rand

Warwick Systems Biology Centre, University of Warwick

Andrew Millar

Daniel Rutherford

Lecture Theatre G27

22nd June 2015

Sébastien Pfeffer

Institut de Biologie Moléculaire et Cellulaire IBMC CNRS

Universite of Strasbourg

Gracjan Michlewski

Daniel Rutherford

Lecture Theatre G27

29th June 2015

Robbie Waugh

Cell and Molecular Sciences, The James Hutton Institute, Dundee

Naomi Nakayama

Daniel Rutherford

Lecture Theatre G27

 

 

 

 

 

Other seminars

Date Event
27th May 2015
12:00
Daniel Rutherford
Lecture Theatre 1 G.27

Tony Carr - University of Sussex

WT PhD Programme Seminar - "Mechanisms of replication-associated genome rearrangement"

A common feature of most cancer cells is genetic instability. We are interested in how this genetic instability occurs. When cancer is initiated by oncogene expression, DNA replication is perturbed and cells experience "oncogene-induced stress" (OIS) during which replication generates DNA damage which activates the p53 checkpoint. This results in a barrier to cancer progression that must be overcome (i.e. through loss of p53) if carcinogenesis is to progress. If this occurs, the resulting cells have an increased propensity to accumulate mutations.

 

OIS can result in the dissociation of the DNA replication machinery from the site of DNA synthesis. If this occurs, replication can be restarted by homologous recombination (HR). Our previous work has demonstrated that HR-restarted DNA replication is intrinsically error prone. We are currently examining the consequences of replicating a region of DNA with a fork that has been correctly restarted by HR. Using DNA polymerase mutants that incorporate excess ribonucleotides we have shown that, following replication restart by HR-dependent mechanisms within S phase, replication is semi-conservative and both strands are synthesises by polymerase delta. We have developed a protocol (Pu-Seq) to map, genome-wide, the usage of Polymerase delta and Polymerase epsilon. Our data plot, at very high resolution, the location of the replication origins and identify regions of the genome where there is increased usage of polymerase delta to replicate the duplex DNA. Such sites may represent regions prone to genome instability.

Host: Kevin Hardwick


22nd May 2015
12:00
Michael Swann Building
S7.20

Pierre-Antoine Defossez, University of Paris-Diderot

Mechanisms of replication-coupled DNA remethylation: a new mechanism for the recruitment of UHRF1

The maintenance of correct patterns of DNA methylation is essential for the survival of mammalian cells. This pattern has to be re-established at each round of DNA replication. One of the key actors in this process is the protein UHRF1: it is essential for DNA remethylation after replication, but its mode of action is unclear.
We have characterised the UHRF1 interactome by proteomics and found that DNA Ligase 1 (LIG1) is a highly abundant interactor of UHRF1. We have mapped the interaction domains and found that a Tudor domain of UHRF1 interacts with an H3-like histone mimic within LIG1. We show that the interaction requires the methylation of the LIG1 histone mimic by the lysine methyltransferases G9a or GLP. Finally, we find that the interaction with LIG1 promotes the recruitment of UHRF1 to sites of DNA replication. These results prompt a reinterpretation of the function of UHRF1's Tudor domain, which we show can bind non-histone proteins. They also reveal a new level of complexity in DNA Ligase 1, identify a new non-histone target of G9a and GLP, and provide the first example of a histone mimic that coordinates DNA replication and DNA remethylation.

Host: Irina Stancheva


20th May 2015
12:00
Daniel Rutherford
Lecture Theatre 1 G.27

Shona Murphy - Sir William Dunn School of Pathology, Oxford

WT PhD Programme Seminar - "The point of no return: a novel Poly(A)-associated elongation checkpoint"

We have uncovered a hitherto-unsuspected kinase-controlled transcription-elongation checkpoint associated with polyadenylation signals at the end of human protein-coding genes. This functions in addition to the well-known CDK9-dependent early-elongation checkpoint at the beginning of genes, and the failure of RNA polymerase II to negotiate this polyadenylation-associated checkpoint aborts transcription elongation prematurely. This checkpoint may provide a final quality-control step for mRNAs at the point of no return, after which a potentially functional mRNA is produced. Polyadenylation-associated checkpoints could therefore provide a powerful and rapid mechanism for the control of transcription in response to a range of signals, such as during development, where synchronous activation and repression of gene expression is required.

Host: Jean Beggs


13th May 2015
12:00
Daniel Rutherford
Lecture Theatre 1 G.27

Cristina Cardoso - Technische Universität Darmstadt, Germany

WT PhD Programme Seminar - "Functional units of DNA replication and repair"

Since the pioneering proposal of the replicon model of DNA replication 50 years ago, the predicted replicons have not been identified and quantified at the cellular level. Here, we combined conventional and super-resolution microscopy of replication sites in live and fixed cells with computational image analysis. We complemented these data with genome size measurements, comprehensive analysis of S-phase dynamics and quantification of replication fork speed and replicon size in human and mouse cells. These multidimensional analyses demonstrated that replication foci in 3D preserved mammalian cells could be optically resolved down to single replicons throughout S-phase. This sets aside the conventional view of replication foci as complex entities corresponding to clustered replicons and establishes the replicon as the elementary functional unit of 3D genome organization. Furthermore, we have combined super-resolution microscopy of DNA damage repair sites with genome-wide ChIP-seq analysis and are testing whether the same elementary units of genome organization underly multiple DNA metabolic processes.

Host: Irina Stancheva


6th May 2015
12:00
Daniel Rutherford
Lecture Theatre 1 G.27

Jon Pines - Gurdon Institute, University of Cambridge

WT PhD Programme Seminar - "How does the cell ensure the fidelity of chromosome segregation in mitosis?"

A dividing cell must ensure that the two daughter cells receive an equal and identical copy of the genome, and this is the focus of our research. We aim to determine how cells regulate entry to mitosis and subsequently coordinate chromosome segregation with cell separation. We know that mitosis is controlled by the interplay between protein kinases, protein phosphatases, and APC/C-mediated proteolysis, and to understand the rapid and complex dynamics of mitosis it is essential to study these processes in living cells, complemented by biochemical analyses. We introduce fluorescent tags into the genes encoding our proteins of interest by homologous recombination to enable us to measure protein numbers and kinetics in vivo, which we can use to inform molecular models.

To understand how proteolysis regulates progress through mitosis we complement the analysis of APC/C-dependent degradation in living cells with biochemical analyses of protein complexes and ubiquitination activity. These studies are revealing how the APC/C is activated and how it is able to select a particular protein for destruction at a specific time. The crucial role of the Spindle Assembly Checkpoint in controlling the APC/C to regulate chromosome segregation has meant that our recent work has elucidated the mechanisms of some of the key steps in the checkpoint pathway, and revealed how the checkpoint is able rapidly to inactivate the APC/C.

Host: Hiro Ohkura


20th Apr 2015
12:00
Daniel Rutherford Building
Lecture Theatre 1 (G27)

Rodney Rothstein, Columbia University

Increased chromosome mobility and the homology search during double-strand break repair

Host: Robin Allshire


16th Apr 2015
12:00
Michael Swann Building
S7.20

Professor Gohta Goshima, Nagoya University, Japan

Microtubules and motors in plants: how do plants manage without centrosomes or dynein?

Host: Hiro Ohkura


20th Feb 2015
12:00
Darwin Lecture Theatre
G10

Martin Wuehr

Proteomic Clues to Cell Organisation

The composition of the nucleoplasm determines the behaviour of key processes such as transcription, yet there is still no reliable and quantitative resource of nuclear proteins. Furthermore, it is still unclear how the distinct nuclear and cytoplasmic compositions are maintained.  To describe the nuclear proteome quantitatively, we hand-isolated the large nuclei of frog oocytes and measured the nucleocytoplasmic partitioning of ~9000 proteins by mass spectrometry. Most proteins localise entirely to either nucleus or cytoplasm, only ~17% partition equally. Native size but not polypeptide-molecular-weight is predictive of localisation: partitioned proteins exhibit native size larger than 100 kDa.  To evaluate the role of nuclear export in maintaining localisation, we inhibited Exportin 1.  This resulted in the expected relocation of proteins towards the nucleus, but only 3% of the proteome was affected. Thus, complex assembly and passive retention, not continuous active transport, is the dominant mechanism for the maintenance of the nuclear proteome.

Host: Julie Welburn


16th Feb 2015
12:00
Daniel Rutherford
Lecture Theatre 1 G27

Titia Sixma - Netherlands Cancer Institute, Amsterdam

WT PhD Programme Seminar - "tbc"

Host: Atlanta Cook


9th Feb 2015
12:00
Daniel Rutherford
Lecture Theatre 1 G27

Chris Smith - Department of Biochemistry, University of Cambridge

WT PhD Programme Seminar - "Understanding the roles of alternative pre-mRNA splicing in shaping smooth muscle cell transcriptomes"

Alternative pre-mRNA splicing is a key molecular mechanism that allows diversification of expressed proteomes far beyond the limitations suggested by a simple "gene-count" of a genome. Many examples of functionally important alternative splicing events have been described, while diseases arising from disruption of alternative splicing show that not only is RNA splicing an essential step in gene expression, but that appropriate regulation of alternative splicing programmes is essential for healthy development. Analyses of alternative splicing have employed both molecular dissection of individual alternative splicing events, as well as global profiling and computational analyses of co-regulated programmes of alternative splicing. I will describe the use of both types of approach by my lab in the analysis of alternative splicing in smooth muscle cells.

Host: Jean Beggs


19th Jan 2015
12:00
Michael Swann
Main Lecture Theatre

Luis Aragon - MRC Clinical Sciences Centre ICL

WT PhD Programme Seminar - "SMC complexes and their chromosomal roles"

Maintenance of genome integrity over cell generations requires the accurate orchestration of key chromosome events during the cell cycle, including genome replication, detection and repair of any DNA lesions and faithful segregation of the chromosome content. SMC protein complexes are important protein complexes for the higher-order manipulation of chromatin and are key contributors to genome stability. Research in our laboratory is focused on the evolutionary conserved SMC complexes cohesin, condensin and Smc5/6, which have crucial roles in chromosome segregation, chromosome-wide gene regulation and recombinational repair. Recently we have developed new proteomic approaches for the identification of SUMOylation on key proteins promoting DNA repair, with particular focus on substrates of the SUMO E3 ligase Nse2, one of the subunits of the Smc5/6 complex. One of the SUMO targets identified as a Smc5/6 substrate is the Bloom helicase Sgs1. Here I will present data showing that Sgs1 SUMOylation depends on Nse2 and is required for HJ dissolution and crossover suppression during double-strand break (DSB) repair.

Host: Bill Earnshaw


16th Jan 2015
12:00
Michael Swann Building
S7.20

David LLobet-Navas, The Mount Sinai Hospital-Icahn Medical Institute, New York, USA

Regulation and function of miR-424/503 in mammary gland development and tissue homeostasis

Despite the established role of a variety of extrinsic and intrinsic signals regulating mammary gland development, a restricted number of studies have identified and validated miRNAs with a role in any aspect of normal mammary gland biology, and even fewer have studied their function using transgenic animal models. Here, we have unveiled the microRNA cluster miR-424(322)/503 as an important TGFb effector that coordinates the massive reorganization that occurs in the mammary epithelium after pregnancy. Furthermore, through the generation of a knock-out mouse model and using in vitro experimental approaches, we have characterized mechanistically its role and regulation in a comprehensive way and linked their alteration to aberrant homeostasis in multiple tissues.

Host: Gracjan Michlewski


12th Jan 2015
12:00
Michael Swann
Main Lecture Theatre

Ana Pombo - Berlin Institute for Medical Systems Biology

WT PhD Programme Seminar - "Hierarchical organization of chromosome folding during mammalian cell differentiation"

Chromosomes have a complex spatial organization within the cell nucleus. They are folded into an array of megabase-sized regions, known as topologically associated domains (TADs), marked by locally enriched chromatin interactions. TADs have internal sub-structures, but their higher-order organization and folding into chromosome territories remains elusive.

 

We have investigated interactions between TADs and find that, far from being isolated structures, they form a functional hierarchy of domains-within-domains (metaTADs), which extends across genomic scales up to entire chromosomes. We map chromatin contacts with Hi-C along a differentiation time-course from proliferating murine embryonic stem cells, through neuronal precursors cells, and terminally differentiated neurons. We find that TAD-TAD interactions generate a hierarchical folding structure irrespective of cell type, reflecting a general organizational principle of the mammalian genome. We explore the mechanisms of hierarchical folding using polymer modelling, and demonstrate that it can promote efficient chromatin packaging without loss of contact specificity. We find that the structures of metaTAD trees correlate with genetic, epigenetic and expression features. The structural rearrangements in metaTAD trees observed during differentiation correlate with changes in transcriptional state, highlighting a functional role for hierarchical chromatin organization far beyond simple packing efficiency.

Host: Adrian Bird


8th Dec 2014
12:00
Darwin Building
Lecture Theatres G10

Pradeepa Marulasiddappa, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh

Role of chromatin and noncoding RNAs in regulating gene expression

Recent ENCODE and GWAS studies suggests association of distal regulatory elements and long noncoding RNAs (lncRNAs) with various diseases. LncRNAs show highly tissue specific expression, however little is known about their specific transcriptional regulation and functional mechanisms.

While investigating the regulation of gene expression by the Psip1/MLL complex, I discovered that Psip1/p52, a transcriptional co-activator which binds to H3K36me3 on the expressed exons, also interacts with splicing factors to modulate alternative splicing. My research also showed that the same protein regulates the transcription of lncRNA Hottip, which in-turn maintains expression of Hoxa genes in cis by recruiting the WDR5/MLL complex. To directly assess lncRNA function in cis, synthetic transcriptional regulators (dCas9-VP160) were recruited to modulate endogenous lncRNA promoters and assessed the regulatory impact on target genes. Further, by editing the Hottip locus, I have recently demonstrated it’s role in regulating Hox gene expression.

Host: Robin Allshire


27th Nov 2014
12:30
Michael Swann Building
S7.20

Federico Pelisch, Centre for Gene Regulation and Expression, University of Dundee

Dynamic SUMO modification regulates chromosome dynamics in the Caenorhabditis elegans embryo

Post-translational modifications including phosphorylation, ubiquitylation and sumoylation are key cell cycle regulators. My main interest is to understand how sumoylation contributes to a timely and accurate cell division. The small ubiquitin-like modifier (SUMO), initially characterised as a suppressor of a mutation in the gene encoding the centromeric protein MIF2, is involved in many aspects of cell cycle regulation. However, the detailed dynamics of conjugation and deconjugation and the mechanisms of action of sumoylation during mitosis remain unexplored. We took advantage of C. elegans to establish the contribution of SUMO to a timely and accurate cell division, using the embryonic first mitotic division as a model. Chromatin-associated SUMO conjugates accumulate during metaphase but decrease rapidly during anaphase. Accumulation of SUMO conjugates on the metaphase plate and proper chromosome alignment depends on the SUMO E2 conjugating enzyme UBC-9 and SUMO E3 ligase PIASGEI-17. Deconjugation is achieved by the SUMO protease ULP-4 and is crucial for correct progression through the cell cycle. Moreover, ULP-4 is necessary for Aurora BAIR-2 localisation to the spindle midzone during anaphase.

By establishing a C. elegans 'SUMO toolkit' for genetics, cell biology, and biochemistry, we have shown that dynamic SUMO conjugation plays a role in cell cycle progression. Currently, I am focusing on the mechanisms by which SUMO regulates chromosome behaviour during mitosis and also meiosis.

Host: David Tollervey


8th Oct 2014
16:00
Michael Swann Building
Main Lecture Theatre

Rudolf Jaenisch, Massachusetts Institute of Technology

iPS technology, gene editing and disease research

Host: Adrian Bird


2nd Oct 2014
16:00
Darwin Lecture Theatre
G10

Ramesh Pillai, EMBL, Grenoble, France

Germline small RNAs for genome defence

Germline-specific Piwi-interacting RNAs (piRNAs) protect animal genomes against transposons and are essential for fertility. piRNAs targeting active transposons are amplified by the ping-pong cycle, which couples Piwi endonucleolytic slicing of target RNAsto biogenesis of new piRNAs. Here, we describe the identification of a transient Amplifier complex that mediates biogenesis of secondary piRNAs in insect cells. Amplifier is nucleated by the DEAD box RNA helicase Vasa and contains the two Piwi proteins participating in the ping-pong loop, the Tudor protein Qin/Kumo and antisense piRNA guides. These components assemble on the surface of Vasa’s helicase domain, which functions as an RNA clamp to anchor Amplifier onto transposon transcripts. We show that ATP-dependent RNP remodeling by Vasa facilitates transfer of 5' sliced piRNA precursors between pingpong partners, and loss of this activity causes sterility in Drosophila. Our results reveal the molecular basis for the small RNA amplification that confers adaptive immunity against transposons.

Host: David Tollervey


2nd Oct 2014
10:00
Michael Swann Building
S7.15

Nonia Pariente, Senior Editor, EMBO Reports

EMBO Press – a look behind the scenes of scientific publishing

The talk will give an insider view of the publication process at journals run by professional editors, from manuscript submission to final decision. Publication policies at EMBO, such as the transparent process and scooping protection, will be also discussed, as well as do’s and don’ts for authors and referees.

Host: David Tollervey


25th Jun 2014
16:45
Michael Swann Building
Main Lecture Theatre

Professor Caroline Dean - John Innes Centre, Norwich

Wellcome Trust PhD Programme in Cell Biology Symposium Lecture - Chromatin and antisense transcript dynamics underlying seasonal timing.

The study of adaptation in plants has led us into the dissection of conserved mechanisms that link antisense transcripts with chromatin dynamics. This work emerged from genetic and molecular analysis of flowering pathways that quantitatively modulate expression of the flowering repressor FLC in response to different environmental and developmental cues.

The antisense transcripts, collectively called COOLAIR, are alternatively spliced and polyadenylated, initiate in an R-loop covering the 3’ end of FLC and encompass the whole FLC sense transcription unit. The differentially processed forms of COOLAIR are associated with different FLC chromatin states via changes in recruitment of chromatin modifying complexes. The talk will describe our current understanding of these mechanisms.

Host: Wellcome Trust PhD Programme in Cell Biology