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Institute of Cell Biology Seminar Series


Seminars will be held on Mondays at 12.05 pm in Lecture Theatre 1, Daniel Rutherford Building.

Seminars in May are held on Wednesdays.

Everyone is welcome to attend.

Semester Two:  January - June 2016





11 Jan 2016

Geert Kops

University Medical Center, Utrecht, The Netherlands

Andrew Goryachev

18 Jan 2016

Paul Lehner

Cambridge Institute for Medical Research, University of Cambridge

Robin Allshire

25 Jan 2016

Ronald Pierik

Institute of Environmental Biology, Utrecht University, The Netherlands


Gerben van Ooijen

1 Feb 2016

Jonathan Higgins

Institute for Cell & Molecular Biosciences, Newcastle University


8 Feb 2016

Kiyoshi Nagai

MRC Laboratory of Molecular Biology, Cambridge

Jean Beggs

15 Feb 2016

Matthias Hentze

EMBL, Heidelberg, Germany

Jean Geggs

22 Feb 2016

Simon Bullock

MRC-LMB, Cambridge University

Hiro Okhura

29 Feb 2016

Thomas Greb

Ruprecht-Karls-Universitat, Heidelberg, Germany

Naomi Nakayama

7 March 2016

KJ Patel

 MRC-LMB, Cambridge

Adrian Bird

14 March 2016

Anna Akhmanova

Department of Biology, Utrecht University, The Netherlands

Julie Welburn

21 March 2016

Renata Basto

Institut Curie, CNRS, Paris, France

Ken Sawin

28 March 2016

Easter Monday


4 April 2016

No seminar (School holidays)


11 April 2016

Jerome Dujardin

Institute of Human Genetics, CNRS

Robin Allshire

18 April 2016


Department of Biochemistry, University of Oxford

Paul Barlow

25 April 2016

To be confirmed


Wed 4 May 2016

Thijn Brummelkamp

The Netherlands Cancer Institute, Amsterdam

Adrian Bird

Wed 11 May 2016

Mary Herbert

Institute of Genetic Medicine, Newcastle University

Adele Martson

Wed 18 May 2016

Dónal O'Carroll

MRC Centre for Regenerative Medicine, University of Edinburgh

David Tollervey

Wed 25 May 2016

Jane Mellor

Department of Biochemistry, University of Oxford

Jean Beggs

6 June 2016

Lori Passmore

MRC-LMB, University of Cambridge

Gracjan Michlewski

13 June 2016

Melike Lakadamyali

Institute of Photonic Sciences, Barcelona, Spain

Julie Welburn

20 June 2016

Helder Maiato

IBMC, Porto, Portugal


Bill Earnshaw

27 June 2016

To be confirmed




Other seminars

Date Event
23rd Feb 2016
Michael Swann Building

Monica Justice, SickKids Research Institute, Toronto, Canada

A suppressor screen in Mecp2 mice reveals pathways for Rett Syndrome pathogenesis

Mutations in the methyl CpG binding protein 2 (MeCP2) cause Rett Syndrome, an X-linked neurological disease with autistic features and developmental regression. Mecp2 mouse mutants provide an excellent animal model to identify molecules that are important for disease pathogenesis. A modifier screen is an unbiased forward-genetic approach to find mutations that suppress or enhance a phenotype of interest, allowing the organism to reveal important pathways for morbidity. We used random unbiased mutagenesis to isolate mutations that suppressed clinical signs and improved overall health in a Mecp2 mouse model. MeCP2 is central to the brain epigenome, so tipping the scale using modifier mutagenesis is highly informative, revealing key pathways for pathology. One modifying mutation showed that cholesterol synthesis was abnormal in Mecp2 mice, and revealed the importance of brain lipid homeostasis to neurological disease. Surprisingly, metabolic syndrome also develops in Mecp2 mice, which can be ameliorated by the administration of statin drugs. Altogether, our data suggest that multiple factors will be required to reverse disease entirely.

Host: Adrian Bird

15th Feb 2016
Daniel Rutherford
Lecture Theatre 1 G.27

Matthias Henze, EMBL, Heidelberg

WT PhD Programme Seminar - "A new view on RNA-binding proteins and RNA"

We recently discovered that hundreds of cellular proteins, previously well known for other biological functions, also unexpectedly bind RNA (termed “enigmRBPs” for enigmatic RNA-Binding Proteins)(1-4). Since many enigmRBPs are conserved from yeast to humans, their existence raises pressing questions. One of the most stunning surprises was the discovery that almost all enzymes of the glycolytic pathway are conserved as enigmRBPs. Overall, more than 50 metabolic enzymes were found to bind RNA. Could the combination of enzymatic and RNA-binding functions represent a general biological principle for coordination between gene expression and metabolism? (5). Applying a newly developed technique, RBDmap, to identify the RNA-binding domains of enigmRBPs, we uncovered new RNA-binding architectures yielding functional insights (6). Integrating all information, we discuss a possible new function for genomes in addition to their classical role in driving protein biosynthesis via mRNAs, rRNAs, and tRNAs and their associated modifying and regulatory RNAs.


(1)   Castello et al., Cell 149, 1393-1406, 2012

(2)   Castello et al., Nature Protoc. 8, 491-500, 2013

(3)   Kwon et al., Nature Struc. Mol. Biol. 20, 1122-1132, 2013

(4)   Beckmann, Horos et al., submitted

(5)   Hentze and Preiss, TiBS 35, 423-426, 2010

(6)   Castello et al., submitted



Host: Jean Beggs

11th Feb 2016
Michael Swann Building

John Weir, MPI of Molecular Physiology, Dortmund, Germany

Biochemical reconstitution and characterisation of a human kinetochore

Chromosomes are carriers of the genetic material and their accurate transfer from a mother cell to its two daughters during cell division is of paramount importance for life. Kinetochores are crucial for this process, as they connect chromosomes with microtubules in the mitotic spindle. Kinetochores are multi-subunit complexes that assemble on specialized chromatin domains, the centromeres, whose unique feature is the enrichment of nucleosomes containing the histone H3 variant centromeric protein A (CENP-A). A group of several additional CENPs, collectively known as constitutive centromere associated network (CCAN), establish the inner kinetochore, whereas a 10-subunit assembly known as the KMN network creates a microtubule-binding site in the outer kinetochore.


Interactions between CENP-A and two CCAN subunits, CENP-C and CENP-N, have been previously described, but a comprehensive understanding of CCAN organization, of how it contributes to selective recognition of CENP-A, and of how it may contribute to propagate centromere identity through subsequent cell generations has been missing. Here, we use biochemical reconstitution of recombinant material to unveil fundamental principles of kinetochore organization and function. We show that cooperative interactions of a 7-subunit CCAN sub-complex, the CHIKMLN complex, determine binding selectivity for CENP-A over H3-nucleosomes The CENP-A:CHIKMLN complex binds directly to the KMN network, resulting in a 21-subunit kinetochore complex. Using a cross-linking and mass-spec approach we elucidate the topology of the complex. Finally we prove that the reconstituted kinetochores are functional, translocating CENP-A nucleosomes to microtubules and that the strength of microtubule binding is influenced by CCAN composition.

Host: Adele Marston

8th Feb 2016
Daniel Rutherford
Lecture Theatre 1 G.27

Kiyoshi Nagai, MRC Laboratory of Molecular Biology, Cambridge

WT PhD Programme Seminar - "Architecture and evolution of the spliceosome: the molecular machine that removes introns from pre-mRNA"

Pre-messenger RNA splicing is catalysed by an intricate molecular machine called the spliceosome and proceeds by a two-step trans-esterification mechanism, analogous to group II intron self-splicing. The spliceosome is assembled on pre-mRNA substrate by the ordered addition of small nuclear ribonucleoprotein particles (snRNPs), U1 snRNP, U2 snRNP and U4/U6.U5 tri-snRNPs and numerous proteins. The fully assembled spliceosome (complex B) undergoes a large structural and compositional change to become catalytically active.  Recent advances in cryo-electron microscopy enabled us to determine the structure of the largest pre-assembled complex, U4/U6.U5 tri-snRNP, at 3.7Å resolution.  This has revealed the complete organisation of the protein and RNA components of this 1.5 MDa assembly.  The structure provides important new insights into the spliceosome activation process leading to the formation of the catalytic centre.

Host: Jean Beggs

18th Jan 2016
Daniel Rutherford
Lecture Theatre 1 G.27

Paul Lehner, Cambridge Institute for Medical Research, University of Cambridge

WT PhD Programme Seminar - "Complementary genetic and proteomic approaches to viral evasion"

The goal of our work is to identify novel genes and map intracellular pathways involved in virus:host cell interactions. Viruses manipulate host cell signaling pathways to enable viral replication and evade immune recognition. In turn, infected cells need to sense and respond appropriately to intracellular viral infections. We have developed a gene discovery platform that involves functional proteomic approaches to identify receptors manipulated by viruses and genome-wide genetic screens to identify key components of intracellular signalling pathways. We use ‘Plasma Membrane Profiling’ to gain an unprecedented overview of cellular receptors manipulated by viruses. TMT-based quantitation allows us to create a temporal cell surface map of receptors manipulated by both integrating (HIV) and non-integrating viruses (HCMV) and established a novel paradigm of viral interference with immunometabolism, through downregulation of amino acid carriers and transporters.


To complement this proteomic approach we use fluorescence-based phenotypic selection for forward genetic screens in human haploid cells. This identified novel genes including (i) ERAD E3 ubiquitin ligases and (ii) the transcriptional repressor complex we termed ‘HUSH’ (Human Silencing Hub) a widely active epigenetic repressor complex that plays a major role in somatic transgene silencing, including the silencing of newly inserted retroviruses.

Host: Robin Allshire

11th Jan 2016
Daniel Rutherford
Lecture Theatre 1 G.27

Geert Kops, University Medical Center, Utrecht, The Netherlands

WT PhD Programme Seminar - Split decisions: Molecular mechanisms for error-free chromosome segregation

 The human body is made up of trillions of cells that exist because of countless successful cycles of cell growth and division during embryo development. These cycles continue during our lifetime to produce cells for tissue renewal and repair. Uncontrolled cell division cycles, however, cause cancer. The Kops lab aims to understand how normal division cycles produce healthy cells and how errors in this process contribute to cancer. Research focusses on the distribution of the chromosomes during the mitotic phase of cell division. Errors in chromosome segregation are a common feature of cancer cell divisions. The lab’s current interests are: 1) how is error-free chromosome segregation ensured at the molecular level? 2) which changes to mitotic processes cause mistakes in cancer cell divisions and how does this impact tumor initiation and development? 3) how have these processes evolved during ~1 billion years of eukaryotic evolution, and can we predict molecular functionalities based on evolutionary conservation or lack thereof?

Host: Andrew Goryachev

23rd Sep 2015
Daniel Rutherford Building
G27, Lecture Theatre 1

Elena Conti

Structural insights into the molecular mechanisms of RNA helicase

RNA helicases are present in all domains of life and participate in virtually all aspects of RNA metabolism. Members of this protein family act as RNA-dependent ATPases in promoting rearrangements of RNAs and/or ribonucleoprotein particles, but are remarkable diverse in their individual functions. Although they share the same catalytic core formed by two domains homologous to the bacterial RecA recombination protein, they are often characterised by additional domains that impart specificity and/or regulation. The talk will address the molecular mechanisms we learnt from studying the structures of DEAD-box and DExH-box helicases, with a particular focus on the exosome-associated helicases Ski2 and Mtr4 and the Drosophila dosage compensation helicase MLE.

Host: Atlanta Cook

13th Jul 2015
Daniel Rutherford Building
Lecture Theatre 1 (G27)

Peter Fraser

Nuclear organization and gene expression control

Host: Eric Schirmer and Philipp Voigt

3rd Jul 2015
Daniel Rutherford Building
Lecture Theatre 1

Chris Ponting, MRC Functional Genomics Unit, University of Oxford

Short steps along the long road to long non-coding RNA function

Thousands of human lncRNA loci have been documented yet only a handful have had their functions experimentally defined.  A large-scale lncRNA knockout project will be required exploiting multiple targeting strategies to determine the full range of contributions that lncRNAs make to human biology and disease.  In the meantime, either computational or experimental investigation of lncRNA loci can provide insights into lncRNA mechanism.

Our investigations of sequence conservation and constraint on lncRNA sequence have previously provided scant evidence for much of this sequence being functional. Nevertheless, we found that such patterns across multi-exonic lncRNA loci mirror those of protein coding genes, although to a lesser degree. Additionally we report strong evidence for the action of purifying selection to preserve exonic splicing enhancers within human multi-exonic lncRNAs and nucleotide composition in fruitfly lncRNAs. Our findings provide evidence for selection for more efficient rates of transcription and splicing within lncRNA loci.

Careful experimental investigations of single lncRNA loci are essential if we are to appreciate the breadth of lncRNA mechanisms. We have identified a mammalian-conserved lncRNA which acts as a microRNA sponge thereby increasing the transcript and protein abundance of mitochondrial oxidative phosphorylation subunits, and hence complex I enzymatic activity. Our experimental and computational approaches demonstrate that many lncRNAs are biologically consequential by regulating gene expression levels in trans either by regulating rates of transcription or levels of transcripts.

Host: David Tollervey

23rd Jun 2015
Darwin Building
Darwin Lecture Theatre (G10)

Professor Tom Owen-Hughes, Centre for Gene Regulation and Expression, University of Dundee

Wellcome Trust PhD Programme in Cell Biology Symposium Lecture - How are nucleosomes organised?


The fundamental subunit of eukaryotic chromatin in the nucleosome consisting of four core histones and 147 bp of DNA. The positions at which nucleosomes deposited on DNA are not random. Arrays of spaced nucleosomes are aligned with genomic features such as transcriptional start sites and the binding sites for sequence specific DNA binding proteins. ATP-dependent motor proteins contribute to the organisation of nucleosomes. To understand how these motors work, we are using combined structural approaches to determine how they engage and alter nucleosomes. We are also studying which motor proteins are responsible for organising nucleosomes in different regions of genomes. For example, in human cells nucleosomes are exceptionally well organised adjacent to the architectural regulator CTCF. We find that complexes containing the enzyme SNF2H play a major role in the organisation of nucleosomes at these sites. A major challenge to the maintenance of stably organised chromatin is the separation of DNA strands during DNA replication. To investigate this we have devised approaches to study how nucleosomes are organised on newly replicated DNA. In budding yeast we find that nucleosomes are organised with respect to transcriptional start sites within minutes of replication. This process does not require transcription indicating the existence of a distinct replication coupled programme for organising nucleosomes. The rate at which nucleosomes are aligned to the transcriptional start site is enhanced at transcribed genes. This supports the existence of periods of increased chromatin organisation activity coupled to the transit of DNA and RNA polymerases. The rapid re-establishment of nucleosome organisation following replication ensures that the chromatin landscape is re-established before newly replicated chromosomes are separated into daughter cells.


Host: Wellcome Trust PhD Programme in Cell Biology

27th May 2015
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

20th May 2015
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
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

12th Jan 2015
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

25th Jun 2014
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