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Events: Seminars
Regular seminars are held on the genome campus and fall into three categories: internal seminars, external seminars and EBI Seminars in Systems Biology. Details of seminars at the Sanger Institute can be found here.
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
10th May 2012 |
| Web Page |
Click here |
| Venue |
Michaelhouse Centre, Cambridge |
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
13th Mar 2012 14:00 |
| Speaker |
Wouter de Laat Hubrecht Institute, Utrecht, The Netherlands |
Abstract/
Additional Info |
Developmental gene regulation in mammals is often controlled
by remote regulatory DNA sequences. ChIP-seq and other functional
genomics profiles indicate the genome is full of potential regulatory
DNA sequences. In order to understand how they are wired to genes,
detailed 3D genome maps are required. I will present our work that aims
to develop improved versions of 3C technology in order to understand how
gene expression is controlled in the 3D nucleus. |
| Venue |
C209-10 |
| Host |
Kathi Zarnack
|
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
28th Feb 2012 14:00 |
| Speaker |
Prof. Juri Rappsilber Wellcome Trust Centre for Cell Biology, University of Edinburgh & Technische Universitat Berlin, Germany |
Abstract/
Additional Info |
Current structural biology methods leave an information gap in the
mid-resolution range at which protein interactions or conformation
changes are defined at domain or sub-domain level. Mass spectrometry in
conjunction with cross-linking is providing exactly this information. We
have applied our tools to complexes up to 670 kDa in size, endogenous,
tagged complexes and even whole cell lysates. We have furthermore
analysed conformation changes in solution using stable isotope labelling
for quantitative analyses.
We have transformed cross-linking/mass spectrometry from an expert
approach to routine application by establishing an integrated workflow
through having: (1) developed an enrichment strategy for cross-linked
peptides based on charge; (2) characterised in detail the fragmentation
behaviour of cross-linked peptides in a high resolution mass
spectrometer; (3) derived lessons from this for a search algorithm that
does not require isotope-labelled cross-linkers and overcomes the n2
problem of database searching for cross-links; and (4) written user
friendly web-based search software that includes a revolutionary
spectrum viewer for match evaluation with implications reaching beyond
this field and a cross-link map viewer for fast hypothesis generation
that expands the current visualisation concepts of protein network
viewers such as used in STRING.
We believe that cross-linking/mass spectrometry is now ready for
deployment into structural and molecular biology laboratories for
routine application.
|
| Venue |
C209 |
| Host |
Rolf Apweiler
|
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
21st Feb 2012 14:00 |
| Speaker |
Kevin Verstrepen VIB Laboratory for Systems Biology and K.U.Leuven Laboratory for Genetics and Genomics, Gaston Geenslaan 1, B-3001 Leuven; Belgium. |
Abstract/
Additional Info |
Organisms need to balance genetic stability and robustness with the ability to evolve and adapt to novel conditions. Cells partly solve this paradox using mechanisms that allow rapid evolution of certain phenotypes, while maintaining other phenotypes robust. We have studied different molecular mechanisms that promote variability and "evolvability" in specific genes.
First, tracts of unstable tandem repeats located within coding regions generate functional variability in genes encoding cell surface proteins and genes involved in regulatory processes. The inherent instability of tandem repeats generates frequent changes in the number of repeat units in the tracts, causing changes in the corresponding protein, and ultimately leading to phenotypic variability. Similarly, unstable tandem repeats located within promoters induce variability in expression of the corresponding gene, which again results in phenotypic variability and evolvability. As such, unstable tandem repeats seem to act as genetic "tuning knobs" that allow rapid evolutionary finetuning of existing genes and regulatory cascades. Remarkably, despite their biological role, repeats are mostly ignored in comparative genomics and GWAS studies, which mostly focus on SNPs and CNVs.
A second mechanism conferring variability to specific phenotypes involves genes located near the chromosome ends. Such subtelomeric genes show massively increased rates of duplication, after which the copies can explore novel functions (neofunctionalization), or evolve towards specialization of separate functions (subfunctionalization). Moreover, subtelomeric genes also undergo frequent ectopic recombination, generating chimeric alleles with novel functions. Hence, subtelomeric regions are breeding grounds for evolutionary innovation.
For more information see: C. Brown et al. Curr. Biology 20: 895; M.D. Vinces et al. Science 324: 1213; Rando and Verstrepen, Cell 128, 655; M. Legendre et al., Genome Research 17: 1787; and Verstrepen et al., Nature Genetics 37: 986. Other manuscripts are in preparation.
|
| Venue |
C209/10 |
| Event Category |
Seminars |
| Event Subcategory |
EBI Pink Seminar |
| Date |
7th Feb 2012 14:00 |
| Speaker |
Jan Korbel |
Abstract/
Additional Info |
In my presentation I will provide an update on current research of my group
in ascertaining the origin and impact of structural variation in healthy
individuals, and disease states. A particular focus will be on somatic
structural variations, which are commonly thought to occur progressively
during cancer development. Recent findings, however, suggest an alternative
mechanism, involving chromosome shattering and reshuffling
('chromothripsis'), the underlying mechanistic basis of which is unknown.
Whole-genome sequencing of a Sonic-Hedgehog medulloblastoma (SHH-MB)
childhood brain tumor from a patient with a germline TP53 mutation
(Li-Fraumeni syndrome) revealed massive, complex rearrangements resulting
from chromothripsis. Integrating TP53 status with genomic rearrangement data
in additional medulloblastomas revealed a striking association between TP53
mutation and chromothripsis in SHH-MBs. Unexpectedly, five seemingly
sporadic SHH-MB patients with chromothripsis harbored TP53 germline
mutations findings relevant for clinical management. Analysis of
additional tumor entities substantiated a link between TP53 mutation and
chromothripsis, beyond general genomic instability. Among these, we observed
a strong association between somatic TP53 mutations and chromothripsis in
acute myeloid leukemia. These findings implicate p53 in the initiation of,
or cellular reaction to, chromothripsis a novel role for the 'guardian of
the genome'. |
| Venue |
M203 |
| Host |
Nick Goldman
|
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
31st Jan 2012 14:00 |
| Speaker |
Dr Johannes Soeding Protein Bioinformatics & Computational Biology at the Gene Center Munich |
Abstract/
Additional Info |
Sequence-based protein function and structure prediction depends
crucially on sequence-search sensitivity and accuracy of the resulting
sequence alignments. In this seminar, I will present HHblits
(HMM-HMM–based lightning-fast iterative sequence search), an
open-source, general-purpose search tool, which represents both query
and database sequences by profile-hidden hidden Markov models (HMMs).
Compared to the PSI-BLAST, HHblits is faster owing to its
discretized-profile prefilter, has 50–100% higher sensitivity and
generates more accurate alignments. It thus has the potential to improve
many downstream analysis and prediction methods. I will first explain
how HHblits achieves its sensitivity and speed and then show benchmarks
and biological applications. I will finish by demonstrating the use of
HHblits on the command line and on the web.
Reference:
Remmert M., Biegert A., Hauser A., and Soding J. Nat. Methods, in press. |
| Venue |
C209/10 |
| Host |
Rodrigo Lopez
|
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
24th Jan 2012 14:00 |
| Speaker |
Nils Bluthgen Institut fur Pathologie Charite - Universitatsmedizin Berlin |
Abstract/
Additional Info |
The EGFR receptor signal transduction network is controlled by a multitude of feedbacks. Most of these feedbacks act negatively on the network's activity, providing robustness, adaptation and homeostasis in the healthy cell. Depending on the feedback strength and structure, different consequences arise if one wants to interfere with the network, such as in cancer treatment. Many small-molecule inhibitors targeting different proteins in the network are available or in (pre-)clinical tests. Thus, the question arises whether one can predict the efficiency and consequences of applying these inhibitors from the feedback structure. If this is possible, one can device a treatment option tailored to the mutational patterns observed in a cancer, giving rise to personalised medicine.
Mathematical modelling predicts that strong feedbacks provide robustness against interference within the pathway. For example, we recently characterised a very strong feedback from ERK to RAF, which renders inhibition of MEK, one of the prime drug targets, inefficient. Upon mutation in RAF (BRAF V600E), this strong feedback is broken, and thus MEK inhibion becomes efficient. Similarly, we find that the response to the RAF-inhibitor Sorafinib is very inefficient unless as long as the feedback is intact.
In an attempt to rationalise and systematize the search and quantitative characterisation of feedbacks and their effects on drug treatment, we set up combined experimental and theoretical screening pipeline. In particular, we use combinatorial perturbation experiments coupled with medium-scale proteomics that allow us to generate coarse-grain semi-quantitative models for feedback regulation. This in turn generates hypothesis that are subsequently followed up by more targeted experiments. For example, this approach predicted a relatively weak feedback from Erk to the EGFR. While weak feedbacks do not hamper drug efficiency, our model predicts other consequence: If one inhibits MAPK siganalling, EGFR is activated and it starts to signal into the AKT pathway. Follow-up experiments confirmed this prediction. Therefore, inhibition of the pro-proliferation MAPK pathway can have the dramatic and undesired consequences as it activates the anti-apoptotic AKT pathway. This suggests that combinatorial treatment is required to successfully commit cancer cells to apoptosis.
|
| Venue |
C209/10 |
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
13th Dec 2011 14:00 |
| Speaker |
Albert Goldbeter Universite Libre de Bruxelles (ULB) |
Abstract/
Additional Info |
I will discuss a detailed computational model for the network of
cyclin-dependent kinases (Cdks) that controls the dynamics of the
mammalian cell cycle. The model contains four Cdk modules regulated by
reversible phosphorylation, Cdk inhibitors, and protein synthesis or
degradation. Growth factors trigger the transition from a quiescent,
stable steady state to self-sustained oscillations in the Cdk network.
These oscillations correspond to the repetitive, transient activation of
cyclin D/Cdk4-6 in G1, cyclin E/Cdk2 at the G1/S transition, cyclin
A/Cdk2 in S and at the S/G2 transition, and cyclin B/Cdk1 at the G2/M
transition. The model accounts for the following major properties of the
mammalian cell cycle: (1) repetitive cell cycling in the presence of
supra-threshold amounts of growth factor; (2) control of cell cycle
progression by the balance between antagonistic effects of the tumor
suppressor pRB and the transcription factor E2F; (3) existence of a
restriction point in G1, beyond which completion of the cell cycle
becomes independent of growth factor; (4) entrainment by the circadian
clock. The model can also account for endoreplication. Incorporating the
DNA replication checkpoint mediated by kinases ATR and Chk1 slows down
the dynamics of the cell cycle without altering its oscillatory nature
and leads to better separation of the S and M phases. The model for the
mammalian cell cycle shows how the regulatory structure of the Cdk
network results in its temporal self-organization, leading to the
repetitive, sequential activation of the four Cdk modules that brings
about the orderly progression along cell cycle phases. I will conclude
by presenting a skeleton, 5-variable model for the Cdk network that can
be seen as the backbone of the more detailed model for the mammalian
cell cycle. It retains similar dynamical properties in regard to its
response to growth factor. Like the detailed model it contains multiple
oscillatory circuits and can display simple as well as complex patterns
of oscillatory behavior. |
| Venue |
C209/10 |
| Host |
Julio Saez-Rodriguez
|
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
6th Dec 2011 14:00 |
| Speaker |
Rickard Sandberg Karolinska Institutet and Ludwig Institute for Cancer Research, Stockholm, Sweden |
Abstract/
Additional Info |
We are studying global aspects of gene regulation by combining
genome-wide experimental and computational techniques to better
understand stem cell characteristics and differentiation processes. In
particular, we are interested in gene expression regulation of
differentiation and cell fates decisions during mouse early embryonic
development. To this end we have been working with single-cell
RNA-Sequencing to obtain single-cell resolution snapshots of the gene
expression program that orchestrate early differentiation. I will in
this seminar present our upnpublished work on single-cell transcriptome
analyses in differentiation and tumorigenesis. In addition, we have
performed a comprehensive assessment of single-cell transcriptomics
using a compendium of well-defined diluted total RNA amounts. This
allowed us to determine the sensitivity and quantitative accuracy in
single-cell transcriptome analyses. Finally, I will present our recently
published findings on a novel link between DNA methylation, CTCF binding
and pre-mRNA splicing. |
| Venue |
C209-10 |
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
29th Nov 2011 14:00 |
| Speaker |
Jean-Loop Faulon ISSB, Genopole |
Abstract/
Additional Info |
Synthetic biology addresses problems beyond classical metabolic engineering by importing pathways from other organisms into microbial chassis. The work presented here will focus on the production of therapeutics with the goal of developing an in situ drug delivery device in host cells. The process consists of implementing a heterologous circuit in E. coli by using retrosynthesis, a concept originally developed for synthetic chemistry, which iteratively applies reversed biotransformations (i.e. reversed enzymes-catalyzed reactions) starting from a target product in order to reach precursors that are metabolites endogenous to the host organism. The proposed method is based on the representation of metabolic maps as annotated hypergraphs where substrates, products and reactions are coded into molecular signatures, which are atomic subgraphs contained in molecular structures and reactions.
The retrosynthesis method that we have developed in my research group searches for heterologous genes and their associated metabolites through the enumeration and ranking of all feasible pathways going from a source set of metabolites to a desired target compound. Candidate pathways are then ranked to select which pathways are best to engineer. The ranking function is based on several criteria such as inhibitory effects, cytotoxicity of heterologous metabolites, and host compatibility (codon usage, homology). Furthermore, the method is making use of several machine learning based predictive tools developed by our group (the MolSig package) in order to estimate enzyme activity and reaction efficiency at each step of the identified pathways.
The retrosynthetic biology approach will be illustrated with the design and experimental implementation of synthetic circuits producing antibacterials in E. coli.
Reference: Carbonell P., Planson A.G., Fichera D., Faulon J.L. A retrosynthetic biology approach to metabolic pathway design for therapeutic production. BMC Systems Biology, 2011, 5:122. |
| Venue |
C209/10 |
| Event Category |
Seminars |
| Event Subcategory |
EBI Pink Seminar |
| Date |
1st Nov 2011 14:00 |
| Speaker |
Kiran Raosaheb Patil |
Abstract/
Additional Info |
Metabolite levels and their turnover rates are the main determinants of cellular metabolic state. Genetic regulation of metabolite levels can only be indirectly exerted through enzyme abundances, which are in turn regulated by various transcriptional, translational and post-translational mechanisms. Elucidation of the link between these regulatory mechanisms and metabolite concentrations is a fundamental challenge in systems biology. To this end, I will present a modeling framework that integrates transcriptomics/proteomics data within metabolic networks and the corresponding mass balance and kinetic constraints. Such a system-level analysis of metabolic networks can significantly contribute towards creating a sustainable (bio-) chemical industry; and for tackling complex, systemic diseases such as type-2 diabetes. |
| Venue |
M203 |
| Host |
John May
If you wish to meet with the
speaker please email John May |
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
25th Oct 2011 14:00 |
| Speaker |
Rolf Muller Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, Campus C2 3 and Department of Pharmaceutical Biotechnology, Saarland University, P.O. Box 151150, 66041 Saarbrucken, Germany |
Abstract/
Additional Info |
Natural product discovery from microorganisms traditionally relies on
the isolation of bioactive compounds from extracts of natural isolates
grown under laboratory conditions. Obviously, this approach almost
completely ignores all types of regulation involved in secondary
metabolite formation and thus falls far short of identifying all
compounds that a given strain is capable of producing. In most cases
major products have been identified only. In the last decade, however,
we have learned that microorganisms established as good natural product
producers carry many more biosynthetic gene clusters in their genomes
than compounds could be isolated from each species to date (1-3).
In the presentation I will discuss our approaches to combine genomic
knowledge with gene inactivation studies and high resolution mass
spectrometry coupled to bioinformatic tools with the aim to ultimately
identify the complete secondary metabolome of each species (4-6).
Studies towards deliberately inducing biosynthetic gene clusters using
regulatory genes will also be described and heterologous expression
based on biosynthetic knowledge (7,8) will be discussed as valid
alternative (2,9). The developed technologies are basically applicable
to every microorganism.
Reference List
1. Bode, H. B. and Muller, R. (2005) Angew. Chem. Int. Ed. 44, 6828-6846
2. Wenzel, S. C. and Muller, R. (2009) Nat. Prod. Rep. 26, 1385-1407
3. Schneiker, S.,et al and Muller, R. (2007) Nat. Biotechnol. 25,
1281-1289
4. Krug, D., Zurek, G., Revermann, O., Vos, M., Velicer, G. J., and
Müller, R. (2008) Appl. Environ. Microbiol. 74, 3058-3068
5. Krug, D., Zurek, G., Schneider, B., Garcia, R., and Muller, R.
(2008) Anal. Chim. Acta 624, 97-106
6. Garcia, R. O., Krug, D., and Muller, R. (2009) Methods Enzymol.
458, 59-91
7. Buntin, K., Irschik, H., Weissman, K. J., Luxenburger, E., Blöcker,
H., and Muller, R. (2010) Chem. Biol. 17, 342-356
8. Dehn, R., Katsuyama, Y., Weber, A., Gerth, K., Jansen, R.,
Steinmetz, H., Höfle, G., Muller, R., and Kirschning, A. (2011) Angew.
Chem. Int. Ed. 50, 532-536
9. Rachid, S., Gerth, K., Kochems, I., and Muller, R. (2007) Mol.
Microbiol. 63, 1783-1796
|
| Venue |
C209/10 |
| Host |
Rolf Apweiler
If you wish to meet with the speaker please email the host
(apweiler@ebi.ac.uk) |
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
18th Oct 2011 14:00 |
| Speaker |
Bernhard Knapp Department for Biosimulation and Bioinformatics, Medical University of Vienna |
Abstract/
Additional Info |
The interaction between the T cell receptor (TCR) and the major
histocompatibility complex (MHC) is an important process in adaptive
immunology. Although a lot of research was done in the last decades the
detailed structural activation mechanism is still not known.
Molecular dynamics (MD) is a standard computational method to solve Newton’s
equations of motion for a given system of atoms over time. These simulations
yield huge trajectories of the atomic coordinates over time. The analysis of
such trajectories is a major challenge in current immunoinformatics.
In this talk I will present our current MD simulations in the context of the
TCR:peptide:MHC interface: I will discuss myelin basic protein peptides in
experimental allergic encephalomyelitis, immunogenic versus non-immunogenic
TCR:peptide:MHC complexes, as well the influence of the peptide flanking
regions in MHC class II.
Some of the recent publications:
B. Knapp, V. Giczi, R. Ribarics and W. Schreiner. PeptX: Using Genetic
Algorithms to optimize peptides for MHC binding. BMC Bioinformatics, 12,
241. 2011
B. Knapp, S. Frantal, M. Cibena, W. Schreiner, P. Bauer. Is an intuitive
convergence definition of Molecular Dynamics simulations solely based on the
Root Mean Square Deviation possible? Journal of Computational Biology, Epub
ahead of print. 2011
B. Knapp, U. Omasits, W. Schreiner, M. Epstein. A comparative approach
linking molecular dynamics of altered peptide ligands and MHC with in vivo
immune responses, PLoS ONE 5(7): e11653, 2010
B. Knapp, N. Lederer, U. Omasits, W. Schreiner. vmdICE: A plug-in for rapid
evaluation of molecular dynamics simulations using VMD. Journal of
Computational Chemistry, 31:2868–2873, 2010
S. Roopra*, B. Knapp*, U. Omasits, W. Schreiner: jSimMacs for GROMACS: a
Java application for advanced Molecular Dynamics simulations with remote
access capability. Journal of Chemical Information and Modeling, 49 (10), pp
2412–2417, 2009 (* equal contribution)
B. Knapp, U. Omasits, B. Bohle, B. Maillere, C. Ebner, W. Schreiner, B.
Jahn-Schmid: 3-Layer-based analysis of peptide-MHC-interaction: in silico
prediction, peptide binding affinity and T cell activation in a relevant
allergen-specific model. Molecular Immunology, 46, 1839-1844. 2009
|
| Venue |
C209/10 |
| Event Category |
Seminars |
| Event Subcategory |
EBI Pink Seminar |
| Date |
4th Oct 2011 14:00 |
| Speaker |
Maja Koehn |
Abstract/
Additional Info |
Protein and second messenger dephosphorylation by phosphatases is
fundamental to a vast number of cellular signalling processes and thus
to physiological functions. Impairment of these processes contributes to
the development of human diseases such as cancer and diabetes. The
investigation of phosphatases is challenging, mainly due to their broad
substrate specificity and the lack of tools to selectively study
particular phosphatases. Despite major accomplishments in the field,
understanding of phosphatase function, regulation and substrate
interaction is in general still limited. The main interest of the lab is
thus to control and investigate phosphatases with the help of chemical
tools, based on phosphoinositide (PIP) and peptide synthetic organic
chemistry as well as with molecular biology approaches. Thereby, we are
focusing on phosphatases that promote diseases. Here, our efforts in
designing probes for PP1, a ubiquitious protein serine threonine
phosphatase, and understanding the actions of PRL-3, a protein tyrosine
phosphatase involved in metastasis formation, will be discussed.
|
| Venue |
M203 |
| Host |
Ben Stauch
If you wish to meet with the speaker please email Ben Stauch
|
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
27th Sep 2011 14:00 |
| Speaker |
Claes Wadelius Department of Immunology, Genetics and Pathology, Uppsala University, Sweden |
Abstract/
Additional Info |
So far we only have a superficial view of which sequences that
participate in gene regulation in the various human cell types. By
ChIP-seq it is possible to study which proteins that bind to the
regulatory sequences and to map the individual nucleosomes in which the
histones carry specific post-translational modifications. Since sequence
is the readout it is possible to correlate signals to genetic variation
and detect allele specific differences in gene regulation. There is set
of modifications that are present at active promoters and our analysis
of histone 3 acetylation at bidirectional and other promoters suggests
that it may be deposited as a consequence of transcription. We have
found that nucleosomes are specifically located over exons and carry
modifications which reflect the expression level of the exon. We have
generated genome-wide maps of nucleosome by deep sequencing of chromatin
treated with MNase I to get further insight into how nucleosome
positions are related to exons and other genomic features. We find that
most of the genome is not packed in nucleosomes with a stable position
which is the same in all analysed cells and that nucleosomes in exons
show specific features. We are mapping genetic variation in HepG2 cells
at high resolution to get the best possible annotation of chromatin. We
believe that these and related methods will aid in integrating data on
genetic variation and quantitative biology. |
| Venue |
C209/10 |
| Event Category |
Seminars |
| Event Subcategory |
EBI External Seminars |
| Date |
20th Sep 2011 14:00 |
| Speaker |
Micaela Zavolan Biozentrum, University of Basel and Swiss Institute of Bioinformatics |
Abstract/
Additional Info |
The discovery of the let-7 miRNA brought into focus an entire layer of
evolutionarily conserved, post-transcriptional regulators of gene
expression. High-throughput experiments revealed their broad impact on
mRNA and protein levels, underlying their essential roles in
development, metabolism, infections and cancers. Experimental
approaches, based on crosslinking and immunoprecipitation, have been
developed to uncover binding sites of RNA-binding protein, including
the Argonautes, that are guided to their targets by microRNAs. Here I
will discuss our attempts to combine large-scale experimental
approaches with computational analyses to uncover the mechanism and
consequences at the celluar level of miRNA-dependent regulation.
|
| Venue |
C209/10 |
| Event Category |
Seminars |
| Event Subcategory |
EBI Pink Seminar |
| Date |
6th Sep 2011 14:00 |
| Speaker |
Detlev Arendt |
Abstract/
Additional Info |
Duplication and divergence of neural circuits in central nervous system
evolution
Neural circuits, composed of interconnected neurons, represent the basic
unit of the nervous system. The highly complex arrangement of
cross-talking, serial and parallel circuits in bilaterian brains can
only be understood if we gain insight into its evolutionary emergence.
In my seminar I will compare the complex circuitry of the vertebrate
forebrain to the much simpler connectome of the marine annelid
Platynereis dumerilii, to pinpoint related neuron types and circuits in
the vertebrate and annelid forebrains and develop hypotheses about their
origin, expansion, duplication and divergence.
|
| Venue |
M203 |
| Host |
Robert Sugar
If you wish to meet
with the speaker please email Robert Sugar |
| Event Category |
Seminars |
| Event Subcategory |
EBI Internal Seminars |
| Date |
30th Jun 2011 16:00 |
| Speaker |
Alvis Brazma EBI |
Abstract/
Additional Info |
I will begin with a very popular introduction into the central dogma of
molecular biology and functional genomics. Then I will briefly talk
about why and how the Microarray Team was created at EBI in late 90’s to
deal with new types of data at the time and how it evolved into the
Functional Genomics ‘multi-team’. Who is doing what, about our work on
ArrayExpress, Gene Expression Atlas and, most recently, on BioSample
Database as well as about our research. I will also briefly touch the
new challenges and the potential applications to biomedicine.
|
| Venue |
M203 (in the Cairns Pavilion) |
| Target Audience |
Although this talk is aimed at newcomers, everyone is welcome to attend. |
| Event Category |
Seminars |
| Event Subcategory |
EBI Postdoc Seminars Day |
| Date |
20th Jun 2011 15:00 |
| Speaker |
David Thybert (Group: Flicek) |
Abstract/
Additional Info |
Relative to exonic sequence or tissue specific gene expression patterns,
transcription factor (TF) binding is poorly conserved in placental
mammals. For example, human and mouse genomes share only 10-20 % of TF
binding regions in liver. To understand the mechanisms behind this rapid
divergence we investigate the initial states of TF binding divergence by
interrogating the overlapping or specific binding regions of three liver
TFs (CEBPa, HNF4a, FoxA1) in five inbred mouse lines separated by less
than 6 million years of evolution. Specifically, we use ChIP-seq to
determine TF binding in two laboratory strains of Mus musculus (C57BL6
and A/J), a sub-species Mus musculus castaneus (1 million years
divergent), and two species Mus spretus (2 million years divergent) and
Mus caroli (6 million years divergent), which was specifically sequenced
for this project. Comparing TF binding at this short evolutionary
timescale allows for more precise estimates on the rate of TF binding
evolution and provides insights into the underlying mechanisms driving
it. We observe a rapid exponential decay of the shared TF location in
liver, resulting in a less than 45% overlap between Mus musculus and Mus
caroli species. By taking advantage of the high degree of DNA sequence
conservation in these genomes, we can investigate the gain and loss of
TF binding events at a nucleotide resolution, and assess the relative
contributions of cis (the sequence) or trans (the cellular environment)
to evolution of TF binding. |
| Venue |
M203 |
| Event Category |
Seminars |
| Event Subcategory |
EBI Postdoc Seminars Day |
| Date |
20th Jun 2011 14:30 |
| Speaker |
Juanma Vaquerizas (Group: Luscombe) |
Abstract/
Additional Info |
The histone acetyltransferase MOF has a dual function as a global
regulator of transcription and dosage compensation in Drosophila.
Whereas it's function in regulating dosage compensation is well
understood, its involvement outside the dosage compensation complex
remains unclear. By integrating genomics data characterising several
chromatin marks and transcriptomics data, we show that the function of
MOF is restricted to the regulation of housekeeping genes. Furthermore,
we propose that this regulation is achieved through nucleosome depletion
of the proximal promoter and specific acetylation at the +1 nucleosome. |
| Venue |
M203 |
|
