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Institute of Cell Biology Seminar Series


Seminars are held on Mondays at 12 noon or Wednesdays in May at 12 noon in Lecture Theatre 1, Daniel Rutherford Building, King's Buildings

Everyone is welcome to attend.


Semester Two:  January - June 2017





9 Jan 2017

Stefan Westermann

University of Duisburg-Essen, Germany

Adele Marston

16 Jan 2017

Amy MacQueen

Wesleyan University, Connecticut, USA

Bill Earnshaw

23 Jan 2017

John Schwabe

University of Leicester

Adrian Bird

30 Jan 2017

Dirk Inzé

Ghent University, Belgium

Gerben van Ooijen

6 Feb 2017

Thornsten Allers

University of Nottingham

Sveta Makovets

13 Feb 2017

Erich Nigg

University of Basel, Switzerland

JP Arulanandam

20 Feb 2017

Philippe Pasero

CNRS, Montpellier, France

Patrick Heun

27 Feb 2017

Patrick Schweizer

Breeding Research, IPK Gatersleben, Germany

Gary Loake

6 March 2017

Anne Donaldson

University of Aberdeen

Sara Buonomo

13 March 2017

Victoria Cowling

University of Dundee

David Tollervey

20 March 2017

Zuzana Storchova

MPIB, Munich, Germany

Adele Marston

27 March 2017

Peter Etchells

University of Durham

Naomi Nakayama

3 April 2017

Mariia Yuneva

The Francis Crick Institute

Sveta Makovets

10 April 2017



17 April 2017



24 April 2017



Wed 3 May 2017

Hiten Madhani

Department of Biochemistry and Biophysics, UCSF, USA

Robin Allshire

Wed 10 May 2017

Béla Novák

Department of Biochemistry, University of Oxford

Adele Marston

Wed 17 May 2017

Danny Reinberg

Howard Hughes Medical Institute, New York, USA

Philipp Voigt

Wed 24 May 2017

Vincent Géli

CRCM, Marseilles, France

Jean Beggs

5 June 2017

Sue Biggins

Fred Hutchinson Cancer Research Center, Seattle, USA

Kevin Hardwick

12 June 2017

Alison Parkin

University of York

Louise Horsfall

19 June 2017

Matthieu Piel

Institut Curie, Paris, France

Julie Welburn

26 June 2017




Seminar details (including ad hoc seminars)

Date Event
22nd Aug 2017
Hudson Beare Building
Lecture Theatre 2

CANCELLED - Tom Misteli, National Cancer Institute, Bethesda, Maryland, USA

Deep Imaging of the Genome

The genome is one of the major physical entities in the eukaryotic cell and is spatially and temporally highly organized. High-throughput imaging approaches are emerging as powerful tools to elucidate the cell biological properties of genomes and to link genome architecture to function at a single-cell level. Deep Imaging methods are based on the development of high-capacity, high-precision automated microscopes which allow acquisition of large imaging datasets and the implementation of computational image analysis and data mining methods to quantitatively capture morphological phenotypes. Deep Imaging enables new experimental strategies for the study of the genome including visualization and analysis of rare events such as chromosome breaks and translocations, use of large-scale imaging-based screens to probe molecular mechanisms of genome organization and function in an unbiased fashion, and they allow mapping of the genome in 3D space. These approaches are powerful tools to probe the cell biology of genomes and provide novel insights into genome architecture and function.

Host: Eric Schirmer

22nd Aug 2017
Waddington Building

Noel Buckley, University of Oxford

Modelling neuronal development with stem cells: from single factors to systems

A major tenet of biology is that development is driven and regulated by networks of transcription factors. This is nowhere more true than during mammalian neurodevelopment where the neural stem cells of the neural plate must ultimately generate the myriad of cell types that constitute the adult nervous system. For several decades we have been driven by the hunt for singular master regulator genes or hubs that drive neurodevelopment and have paid scant attention to the networks in which the regulators operate. I will review both these approaches using our work on REST as an exemplar of a master transcription factor that regulates a myriad of biological processes and then introduce our recent attempts to develop dynamical networks using a state-space modelling approach incorporating time-delay to provide a systems perspective of neural induction.

Host: Adrian Bird

7th Aug 2017
Waddington Building

Song Tan, Pennsylvania State University

Structural studies of chromatin complexes

Song Tan is Professor of Biochemistry & Molecular Biology at Penn State University in the U.S..  He studied physics as an undergraduate at Cornell University (1985) before pursuing his PhD at the MRC Laboratory of Molecular Biology (1989).  He continued his training as postdoctoral fellow and project leader under Tim Richmond at the ETH-Zürich (Swiss Federal Institute of Technology) where he determined crystal structures of transcription factor/DNA complexes.  Dr. Tan joined the Penn State Department of Biochemistry and Molecular Biology in 1998.  Dr. Tan’s laboratory investigates how chromatin enzymes and factors interact with their nucleosome substrates through biochemical and structural approaches.  His laboratory determined the first chromatin factor-nucleosome crystal structure (RCC1-nucleosome) in 2010 and the first chromatin enzyme-nucleosome crystal structure (PRC1-nucleosome) in 2014.  He recently spent a year on sabbatical at the MRC LMB to learn cryoEM.

Host: Robin Allshire

14th Jul 2017
Waddington Building

Ingmar Schaefer, Max-Planck Institute for Biochemistry

Molecular mechanisms of Pan2-Pan3 activity in the regulation of poly(A) tail length

The poly(A) tail is an almost universal post-transcriptional modification present at the 3’ end of eukaryotic mRNAs. Its length is a hallmark of posttranscriptional regulation and affects the mRNAs’ nuclear export, translation and decay. The poly(A)-tail is a dynamic modification: it is added by polyadenylate polymerases and removed by deadenylases. The conserved Pan2-Pan3 deadenylase complex is recruited to poly(A) tails via the interaction with the cytoplasmic poly(A) binding protein, PABP. Here, the Pan2-Pan3 nuclease catalyzes the trimming of the poly(A) tail, which is the initial and rate limiting step of canonical eukaryotic mRNA turnover. The molecular mechanisms of the recruitment of Pan2-Pan3 to poly(A)-tails, the regulation of its deadenylase activity and the impact of this substrate-nuclease system on global cellular poly(A) distributions still remain unclear. Using cryo-EM structural approaches and biochemical assays, we are studying the substrate requirements for Pan2-Pan3. We found that poly(A)-tail length and PABP binding impact on the recruitment and activity of Pan2-Pan3. The structural and biochemical observations correlate with earlier in vivo findings of global poly(A) tail length regulation and suggest a model where Pan2-Pan3 in concert with PABP is key for maintaining steady-state poly(A)-tail length distributions in cells.

Host: Atlanta Cook

5th Jul 2017
Waddington Building

Ian Wilson, The Scripps Research Institute, La Jolla, USA

Structure-based Design of Universal Vaccines and Therapies against Influenza Virus

Until relatively recently, most antibodies to influenza virus were thought to be strain-specific and protect only against highly related strains within the same subtype. Since 2008, many human antibodies have been isolated that are much broader and neutralize across different subtypes and types of influenza viruses through binding to functionally conserved sites. The major surface antigen, the hemagglutinin (HA), of influenza virus is the main target of these neutralizing antibodies. We have determined crystal structures of several broadly neutralizing human antibodies in complex with variety of different HAs and show they bind to the highly conserved functional sites on the HA fusion domain (stem) in influenza A as well as influenza B viruses, as well as to the receptor binding site. The characterization of these broadly neutralizing antibodies along with their mode of binding and neutralization has provided exciting new opportunities for structure-assisted vaccine design and for design of therapeutics that afford greater protection against influenza viruses. Indeed, a mini-HA immunogen that was designed to mimic the highly conserved HA stem elicited a protective response against different influenza subtypes, such as H1N1 and H5N1, in mice and monkeys and is a promising proof of concept for development of a more universal flu vaccine. We also recently determined the structure of a broad anti-viral small molecule arbidol and elucidated its binding site and mechanism of action.

Host: Atlanta Cook

24th May 2017
Daniel Rutherford
G.27, LT1

Vincent Gèli, CRCM, Marseilles, France

WT PhD Programme Seminar - The many faces of the Set1 complex

The family of histone H3 lysine 4 (H3K4) methylases is highly conserved from yeast to human. They share a canonical organization in which the catalytic subunit acts as a docking platform for multiple subunits that regulate the enzymatic activity. Set1 complex (Set1C or COMPASS) mediated H3K4 methylation is one of the most prominent histone modifications that mark active transcription. In budding yeast, Set1C and H3K4 methylation have not only been involved in transcription but in multiple processes such as chromosome segregation, DNA replication, and meiotic recombination. Recent reports led to the concept that Set1C subunits, in addition to regulating H3K4 methylation, may be directly involved in some of these biological functions by recruiting specific protein partners. However, the mechanisms by which the Set1C protein interaction network promotes these processes remain poorly understood. In this talk, we will discuss these many faces of the Set1 complex.

Host: Jean Beggs and Bella Maudlin

17th May 2017
Daniel Rutherford
G.27, LT1

Danny Reinberg, Howard Hughes Medical Institute, New York, USA

WT PhD Programme Seminar - Epigenetics: One Genome, Multiple Phenotypes

Epigenetics encompasses changes in gene expression profiles that occur without alterations in the genomic DNA sequence of a cell. This arises from the dynamic processes that structure regions of chromosomal DNA through a range of compaction in eukaryotes. The altered pattern of gene expression is pivotal to cellular differentiation and development and is inherited by daughter cells thereby maintaining the integrity, specifications, and functions for a given cell type.  Aberrancies in this epigenetic process give rise to perturbations that are also inherited and disruptive to normal cellular properties.

Host: Philipp Voigt and Elana Bryan

10th May 2017
Daniel Rutherford
G.27, LT1

Bèla Novàk, Department of Biochemistry, University of Oxford

WT PhD Programme Seminar - Cell cycle regulation by systems-level feedback controls

In order to maintain genome integrity and an effective nucleocytoplasmic ratio from one generation to the next, cells carefully monitor progression through their replication-division cycle and fix any errors before they jeopardize the progeny of the cellular reproduction process. These error surveillance and correction mechanisms operate at distinct ‘checkpoints’ in the cell division cycle, where a growing cell must ‘decide’ whether it must wait for errors to be corrected or it may proceed to the next phase of the cell cycle. Once a decision is made to proceed, the cell unequivocally enters into a qualitatively different biochemical state, which makes cell cycle transitions switch-like and irreversible. These characteristics of cell cycle transitions are best explained by bistable switches with different activation and inactivation thresholds, resulting in a hysteresis effect. Almost 25 years ago, John Tyson and I proposed that the activity of the mitosis-inducing protein kinase, Cdk1:CycB, is controlled by an underlying bistable switch generated by positive feedbacks involving inhibitory phosphorylations of the kinase subunit. Numerous predictions of this model were experimentally verified by different groups, and bistability has become a paradigm of cell cycle transitions. The phosphorylation of mitotic proteins by Cdk1:CycB is counteracted by a protein phosphatase, PP2A:B55, which is inhibited during mitosis by a stoichiometric binding partner, ENSA-P, which is itself activated by Greatwall-kinase. Using mathematical modelling guided by biochemical reconstitution experiments, we showed recently that the BEG (B55-ENSA-Greatwall) pathway also represents a bistable, hysteretic switch controlled by the activity of Cdk1:CycB. Bistable regulation of the kinase (Cdk1:CycB) and the phosphatase (PP2A:B55) makes hysteresis a robust property of mitotic control, with suppression of futile cycling of protein phosphorylation and dephosphorylation during M phase.  These considerations show that both entry into and exit from mitosis are controlled by bistable switches intimately connected to the activities of the major mitotic kinase, Cdk1:CycB, and phosphatase, PP2A:B55. Intriguingly, the ‘design principle’ of the BEG pathway is operative as well at two other cell cycle checkpoints, as will be discussed.

Host: Adele Marston

3rd May 2017
Daniel Rutherford
G.27, LT1

Hiten Madhani, Department of Biochemistry and Biophysics, UCSF, USA

WT PhD Programme Seminar - Epigenetic memory over geological timescales

This seminar will describe a DNA methylation system in the yeast Cryptococcus neoformans that displays strong functional similarities to the mammalian Dnmt1-dependent maintenance methylation system. Results demonstrating that the yeast system operates in a "maintenance-only" fashion will be presented. These findings raise the question of when methylation was initially established. Additional results will be described that shows that DNA methylation was established in an ancestor species that lived 50-150 million years ago by a de novo methylase whose gene was subsequently lost from the genome.

Host: Robin Allshire

28th Apr 2017
Michael Swann Building

Lars Jansen, Instituto Gulbenkian de Ciencia, Oeiras, Portugal

Chromatin-based epigenetic inheritance

The Jansen Lab aims to resolve fundamental mechanism of epigenetic inheritance. They have built expertise in determining the contribution of histone variants to chromatin-based epigenetic memory with a focus on the human centromere and the maintenance of active transcription as well as the impact of epigenetic silencing on evolution. Using innovative and multi-angled approaches that include mammalian somatic and stem cell biology, yeast genetics, high-end imaging tools and genome engineering they address a broad set of questions related to chromatin-based epigenetic inheritance.

Host: Robin Allshire

20th Mar 2017
Daniel Rutherford
G.27, LT1

Professor Zuzana Storchova - Max Planck Institute of Biochemistry, Munich

Monday Seminar Series - "The consequences of aneuploidy: From Down’s syndrome to cancer"

Faithful duplication of chromosomes and their equal segregation into daughter cells is essential for survival of any organism on earth. Errors during chromosome segregation lead to chromosome gains and losses – the resulting daughter cells contain abnormal numbers of chromosomes, they become aneuploid. Aneuploidy is the major cause of spontaneous miscarriages. Moreover, more than 80 % of malignant tumors contain cells with aneuploid karyotype. 


We have developed a model system of defined aneuploidies in human cells. In this lecture I will review our results that provide new insights about how abnormal chromosome numbers affect eukaryotic cells and how these changes may contribute to tumorigenesis.

Host: Adele Marston

13th Mar 2017
Daniel Rutherford
G.27, LT1

Professor Victoria Cowling - School of life Sciences, University of Dundee

Monday Seminar Series - 'mRNA cap regulation in pluripotency and differentiation'

mRNA caps are a collection of structures which select transcripts for processing and translation.  We investigate how cellular signalling pathways regulate mRNA cap formation by influencing capping enzyme expression, activity and localisation.  Formation of the initial mRNA cap structure, 7-methylguanosine, is completed by RNMT-RAM.   RNMT is the cap methyltransferase common to all eukaryotes.  Vertebrates also express RAM, a RNMT-activating subunit.   The talk will cover the role of RAM in the maintenance of pluripotency in embryonic stem cells and its role in neural differentiation.  In embryonic stem cells, RAM expression is high and is required for pluripotency-associated gene expression.  During differentiation, ERK1/2-dependent phosphorylation results in RAM degradation, which is required for the emergence of neural precursors.  In addition to its role in mRNA cap methylation, we have discovered a role for RAM in gene-specific transcription.  In embryonic stem cells, RAM has a global impact on translation and also co-ordinates the expression of pluripotency-associated genes.

Host: David Tollervey

28th Feb 2017
Michael Swann

Mohan Balasubramanian, Biomedical Sciences, University of Warwick

Cytokinesis in vitro and in vivo

Host: Ken Sawin

23rd Feb 2017
Michael Swann

Gavin Kelsey, Babraham Institute

Transcription as a driver of epigenetic transitions in the oocyte

Chromatin organisation is fundamental to genomic regulation, of which histone modifications are an integral part, however, it remains unclear to what extent histone modifications are an instructive component of the epigenetic landscape. The oocyte provides an attractive system to investigate temporal aspects of epigenetic regulation, because of the extensive epigenetic remodelling that occurs in a non-dividing cell; moreover, chromatin states in the oocyte may inform gene regulation in the zygote. Using new ultra low input chromatin immunoprecipitation methods to interrogate histone modifications throughout oogenesis, we observe widespread reprogramming of H3K4me3 in early oocytes, which subsequently accumulates independent of transcription. A consequence of the widespread deposition of H3K4me3 was the generation de novo of bivalent promoters and loss of canonical enhancer marks. Using conditional knock-outs to ablate H3K4me3 or DNA methylation in oocytes revealed, unexpectedly, that DNA methylation was dominant over H3K4me3 deposition. These results suggest that histone remodelling is not a driver of genomic regulation in the oocyte, but reflects transcriptional activity and targeting of DNA methylation.

Host: Adrian Bird

20th Feb 2017
Daniel Rutherford
G.27, LT1

Dr Philippe Pasero - Institute of Human Genetics, CNRS, Montpellier

Monday Seminar Series - "SAMHD1 acts on replication stalled forks to prevent chronic inflammation"

SAMHD1 is a dNTPase that restricts HIV-1 infection in non-cycling cells. Mutations in SAMHD1 cause Aicardi-Goutières syndrome (AGS), a severe inflammatory disease, and have also been implicated in chronic lymphocytic leukemia (CLL). However, the molecular mechanisms by which SAMHD1 prevents inflammation and cancer development remain unknown.


We have characterized a novel function of SAMHD1 in DNA replication that is independent of its dNTPase activity. We have found that SAMHD1 promotes the degradation of newly-synthesized DNA at arrested replication forks. This activity is required for checkpoint activation and for the recovery of stalled forks, indicating that SAMHD1 is a novel key player of the replication stress response. Remarkably, we also found that newly-replicated DNA diffuses out of the nucleus and accumulates in the cytosol in the absence of SAMHD1, leading to the activation of a type I interferon response. Together, these data indicate that SAHMD1 promotes fork restart and prevents inflammation by degrading ssDNA fragments produced by fork repair processes.

Host: Patrick Heun

13th Feb 2017
Daniel Rutherford
G.27, LT1

Professor Erich Nigg - Biozentrum, University of Basel

Monday Seminar Series - "Cell Cycle Control of Chromosome Segregation: Focus on Kinetochores and Centrosomes"

The error-free segregation of duplicated chromosomes during cell division is crucial to the development and health of all organisms. Conversely, chromosome mis-segregation is held responsible for causing human disease, including cancer. Chromosome aberrations are thought to result from the deregulation of mitotic progression, a defective spindle assembly checkpoint, and/or centrosome abnormalities. Our laboratory is interested in the cell cycle control of chromosome segregation, with particular emphasis on the function of kinetochores and the regulation of the centrosome duplication cycle. In the first part of my talk, I will briefly summarize our recent work on the role of the Ska complex in mediating kinetochore-microtubule interactions during mitosis. Our results lead us to propose that the Ska complex promotes Aurora B activity to limit its own microtubule and kinetochore association, thereby ensuring that the dynamics and stability of kinetochore microtubules fall within an optimal range for chromosome bi-orientation on the spindle apparatus.

In the second part of my talk I will focus on the centrosome duplication cycle. Centrosomes organize microtubule arrays important for cell shape, polarity and motility as well as chromosome segregation. Moreover, the core components of centrosomes, the centrioles, are essential for the formation of cilia. Centrosome and centriole aberrations have been implicated in tumorigenesis, ciliopathies, microcephaly and dwarfism. I will briefly summarize our current understanding of the mechanism underlying centriole duplication in human cells, with particular emphasis on a core module that comprises the protein kinase Plk4, its substrate STIL, and the cartwheel component Sas-6. I will then focus on the regulation of STIL abundance during the cell cycle, and present data that lead us to propose that centriole amplification may constitute one root cause of primary microcephaly. Finally, I will summarize our recent work aimed at a quantitative understanding of centrosome architecture. To measure the abundance of key centrosomal proteins within cells and at the centrosome, respectively, we have combined targeted proteomics with EGFP-tagging of selected proteins at endogenous loci. Our results provide a first assessment of the absolute and relative amounts of major components of the human centrosome.

Host: JP Arulanandam

25th Jan 2017
Michael Swann Building

Michael Markie, Wellcome Open Research

Wellcome Open Research: a new publishing initiative from the Wellcome Trust

Wellcome Open Research is a new publishing platform that provides all Wellcome researchers with a place to rapidly publish any results they think are worth sharing.


Based on the F1000Research publishing model, Wellcome Open Research will make research outputs available faster and in ways that support reproducibility and transparency. It uses an open access model of immediate publication followed by transparent, invited peer review and inclusion of supporting data. It encourages the publication of all research outputs including data sets, negative results, protocols, case reports, incremental findings as well as more traditional narrative-based articles.


This 20 minute presentation by Michael Markie (Publisher, Wellcome Open Research) will discuss the aims and motivations for establishing this platform, how it works and the benefits it offers to researchers. The presentation will then be followed by the opportunity to ask questions and discuss the platform.

Host: Wellcome Trust Centre for Cell Biology

23rd Jan 2017
Daniel Rutherford
G.27, LT1

Professor John Schwabe - Department of Molecular and Cell Biology (formerly Biochemistry), Henry Wellcome Laboratories of Structural Biology,
 University of Leicester

Monday Seminar Series - "The molecular mechanisms of epigenetic transcriptional repression complexes"

My research group seeks to understand the molecular mechanisms that underlie the epigentic reprogramming of the genome during cellular differentiation and development. Our particular interest is in Histone Deacetylase (HDAC) complexes whose primary role is to remove acetyl groups from lysine sidechains within the tails of histone proteins resulting in hypo-acetylated chromatin that is associated with inactive or repressed genes.

There are at least five classes of HDAC-containing complexes that are targeted to chromatin. These contain the class I HDACs 1, 2 or 3 along with a variety of other proteins that target the complex to chromatin and/or possess other enzymatic activities. Importantly, the enzymatic activity of the HDACs requires assembly into these complexes.

Our structural and functional studies have given insight into the assembly and mechanism of action of these complexes. The crystal structure of HDAC3 in complex with its cognate co-repressors SMRT revealed, quite unexpectedly, that this complex is regulated by inositol phosphate. Studies of further HDAC complexes suggests that such regulation is a common theme. We are also exploring the assembly of several entire HDAC complexes and are beginning to understand their mode of assembly and the cross-talk between different components.

Host: Adrian Bird

19th Jan 2017
Michael Swann

Roy A Quinlan, University of Durham

Crafting "function" from "form" using cell proliferation and the cytoskeleton in the eye lens

The eye lens is a deceptively simple tissue, but it is a prime example of the D¹Arcy Thompson principle that "Form and Function” are linked. Our research addresses fundamental questions such as how do cells know their relative position in a tissue? What emergent properties are important for tissue formation? We believe that at least part of the answer to these questions lies in the lens epithelium. It is here that the iconic hexagonal shape of the lens fibre cells is established and the consequential spatial order established. During development this is easy to rationalize as the lens increases layer by layer onto a preformed template, but what happens when the lens regenerates? What determines the organization of the lens fibre cells in that scenario? We have built an interdisciplinary research team (John Girkin, Chris Saunter (Physics), Junjie Wu and Boguslaw Obara (SECS) with skills needed to study cell dynamics in the living zebrafish and in regenerating rat lenses. We have produced a mathematical model for the lens epithelium and we hope eventually to have a finite element model for lens accommodation. Along the way, we are studying the role of the intermediate filament cytoskeleton and their associated protein chaperones in maintaining lens optical functions, their effects upon cell shape and how ageing and disease affect their respective functions. The eye lens is a system that illuminates all the major key biological questions on ageing, cancer prevention, apoptosis as well as protein longevity. I shall select examples from my research portfolio to illustrate how form and function are linked so perfectly in the eye lens.

Host: Eric Schirmer

16th Jan 2017
Daniel Rutherford
G.27, LT1

Dr Amy MacQueen - Molecular Biology and Biochemistry, Wesleyan University

Monday Seminar Series - "Zippers and Stitches in the Meiotic Nucleus"

Our research seeks to understand the long mysterious but fundamental cellular mechanisms that drive chromosome dynamics during the differentiation of sex cells. A critical feature of sex cell differentiation is a reduction in chromosome number. During the specialized cell division cycle called meiosis, homologous partner chromosomes somehow identify and specifically associate with one another, and this association ensures their accurate segregation into separate chromosomal complements. A longstanding cell biological mystery is:  How does a chromosome search for and ultimately recognize its proper homologous partner in the nucleus? We use genetic, cytological, and biochemical approaches in conjunction with high resolution microscopy to identify the molecules and mechanisms that underlie how meiotic chromosomes interact, how homology detection occurs, and how homology recognition is coordinated with chromosome pairing reinforcement in the budding yeast, Saccharomyces cerevisiae.


            A transient yet dramatic reinforcement of initial homologous chromosome pairing occurs via the zipper-like assembly of a tripartite structure, the synaptonemal complex (SC), at the interface of lengthwise-aligned meiotic chromosomes. SC assembly between homologous chromosomes accompanies meiotic double strand break repair events at discrete sites along chromosomes; such homologous recombination events include crossovers (“stitches”), which splice DNA molecules of independent homologous chromosomes and serve to link homologs until their orientation and segregation on the meiosis I spindle. Past studies from our lab revealed several fundamental architectural and dynamic aspects of the budding yeast SC, as well as regulators that ensure SC assembles “at the right place, at the right time”. Our more recent studies have explored the functional relationship between the SC structure, its protein components, and meiotic recombination in budding yeast. Our observations suggest that many of the building block components of the budding yeast SC have distinct functions in meiotic recombination that may have evolved independently of their roles in SC assembly per se. An intriguing set of data indicates that an SC transverse filament protein, Zip1, may be mechanistically involved in crossover recombination in a manner that overlaps the activity of the MutS complex. Another observation reveals that the SC central element proteins, Ecm11 and Gmc2, promote proper mismatch repair during meiotic recombination. Our research is currently focused on experiments aimed at discovering the molecular features and underlying mechanisms that link such SC structural proteins to their essential roles in meiotic recombination.

Host: Bill Earnshaw

9th Jan 2017
Daniel Rutherford
G.27, LT1

Professor Stefan Westermann - Center of Medical Biotechnology, Department of Molecular Genetics, University of Duisburg-Essen

Monday Seminar Series - "Kinetochores and the microtubule cytoskeleton: Biochemical and genetic analysis of chromosome segregation in budding yeast"

Centromeres direct the assembly of kinetochores, microtubule-attachment sites thatallow chromosome segregation on the mitotic and meiotic spindle. I will discuss current projects in the lab that aim to elucidate the molecular organization of these chromosome segregation machines through a biochemical and genetic analysis of the budding yeast kinetochore. We have biochemically reconstituted large parts of the yeast kinetochore, including a full-length ten-protein KMN network. Current projects in the lab address how KMN is anchored to centromeric chromatin through association with multiple recruiters such as the CENP-C homolog Mif2, the AO complex and the CENP-T homolog Cnn1.

In addition, we are combining biochemical reconstitution experiments with single-molecule fluorescence microscopy to analyze mechanisms of microtubule-based motility. To this end we have performed a detailed analysis of the kinesin-14 protein Kar3, a minus-end directed molecular motor involved in microtubule organization and kinetochore transport. We are asking how the unusual biophysical properties of the Kar3 motor, whose movement depends on a non-catalytic domain, contribute to microtubule organization and kinetochore function.

Host: Adele Marston

23rd Nov 2016
Michael Swann Building

Mark C Field, University of Dundee

Evolution of the nuclear envelope - proteomics and comparative genomics to reconstruct the NPC and lamina

Host: Robin Allshire

22nd Nov 2016
Michael Swann Bulding

Andreas Ladurner, Ludwig-Maximilians-Universitat Munchen

Poly-ADP-ribose releases the autoinhibition of the oncogenic chromatin remodeler Alc1

Chromatin remodeling enzymes are essential in order to establish, alter or maintain eukaryotic chromatin structure and function. Their recruitment to the chromatin template is regulated by the presence of globular proteins domains capable of recognizing post-translationally modified histones, such as specific acetyl-lysine or methyl-lysine marks recognized by bromodomains and chromodomains, respectively. Increasing evidence, however, also suggests that post-translational modifications regulate the enzymatic activity of remodelers, and not just their recruitment. We will present unpublished work showing that the enzymatic activity of the human poly-ADP-ribose-dependent nucleosome remodeler Alc1/Chd1L is regulated exquisitely by oligomeric ADP-ribose ligands. Specifically, we find that tri-ADP-ribose binds the C-terminal macrodomain of the remodelers with nanomolar affinity, which in turns leads to a loss of intramolecular interaction with the catalytic Snf2 domain of the remodelers ATPase. ITC assays, MS-coupled H/D-exchange measurements, site-directed mutagenesis as well as real-time, live-cell imaging provide molecular insight into the allosteric activation of this remodeler mediated by oligomeric forms of ADP-ribose. Our data provide a mechanistic basis for Alc1/Chd1L’s function as an exquisite sensor of the DNA-damage-induced and PARP1-mediated synthesis of poly-ADP-ribose, fully consistent with the rapid recruitment of Alc1/Chd1L to DNA damage sites in live cells. Our data reveal an unprecedented mechanism for the ligand-induced, allosteric regulation of a critical remodeling enzyme and oncogene.

Host: Philipp Voigt and Atlanta Cook

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