Mechanics, topology and geometry of mammalian chromosomes and nuclei and their modulation by histone epigenetic marks

Our lab uses biophysical methods, with particular emphasis on micromanipulation of single DNA molecules and single chromosomes, to study the internal structure of chromosomes in vivo, and to study chromosome-organizing proteins and DNA topoisomerases in vitro. We also develop mathematical models ...

An ancient machinery drives piRNA transcription in C. elegans

Piwi-interacting RNAs (piRNAs) engage Piwi proteins to suppress transposons and nonself nucleic acids and maintain genome integrity and are essential for fertility in a variety of organisms. In Caenorhabditis elegans, most piRNA precursors are transcribed from two genomic clusters that contain th...

Integration of Glycomics, Development, and Immunology

Ludger Johannes has invited  Pr Richard D. Cummings from Beth Israel Deaconess Medical Center Harvard Medical School to come and give a talk on "Integration of Glycomics, Development, and Immunology". He will also participate in the Pastor's course

Precise and imprecise therapeutic targeting of sarcomas across the age spectrum

The biological and clinical diversity of sarcomas represents both a scientific opportunity and a medical challenge.  Although cytotoxic chemotherapy can be curative for an important subset of patients, advances in technology have allowed us to identify mechanisms of oncogenic drivers and therapeu...

Late stage (radio)fluorination. Lessons to be learned from the fluorinase enzyme

The impact of fluorine chemistry in the life sciences is enormous.  As many as 30−40% of agrochemicals and 20% of pharmaceuticals on the market are estimated to contain fluorine. 19F- and 18F-labelled compounds are also finding increasing applications in imaging such as Magnetic Resonance I...

Regulation of Replication Timing and Chromosome Architecture

The temporal order of DNA replication (replication timing, RT) is highly coupled with genome architecture, but cis-elements regulating spatio-temporal control of replication have remained elusive. We performed an extensive series of CRISPR mediated deletions and inversions and high-resolution cap...

Marie Curie Seminar: Christiane Nüsslein-Volhard - How fish colour their skin: A paradigm for development and evolution of adult patterns

Colour patterns are prominent features of most animals; they are highly variable and evolve rapidly leading to large diversities between species even within a single genus. As targets for natural as well as sexual selection, they are of high evolutionary significance. The zebrafish (Danio rerio) ...

The role of phase separation in organising cellular biochemistry

We are actively studying the physical mechanisms of phase separation in the lab, using biophysical, genetic, and chemical methods. The principles of phase separation also inform our understanding of the formation of centrosomes, another active area of research in the lab. Click the buttons below ...

Gastrulation through a primitive streak : cellular mechanisms & signals

Amniote (birds and most mammals) embryos have the remarkable ability to undergo “embryonic regulation”: this is a property by which a fragment of the embryo can reconstitute the entire embryo. This can occur right up to the appearance of the primitive streak (14th day in humans), and ...

Networks based approaches in epigenomics, evolution and biomedicine

Network biology, a growing field of Computational Biology, opens great new possibilities for the study of complex biological systems. In this presentation, I will review four specific cases of the application network approaches. In the first study, we processed heterogeneous ChIP-Seq informati...

Models and model systems: the nutritional geometry of health and ageing

The question of what represents a balanced diet and how this maintains health and longevity remains unanswered. The talk will set out an integrative framework, Nutritional Geometry, for describing the multidimensional nature of nutritional requirements, the relative values of foods in relation to...

DNA replication stress and cancer

Genomic instability is one of the most important factors driving cancer progression and resistance to therapy. Oncogenes, by inducing DNA replication stress, are a critical factor underlying genomic instability in cancer, but the mechanisms by which oncogenes cause DNA replication stress have rem...

What flies can and can’t teach us about piRNAs

In animals, PIWI-interacting RNAs (piRNAs) serve as guides for the PIWI clade of Argonaute proteins, an evolutionary conserved family of RNA-binding proteins at the heart of eukaryotic gene silencing pathways. Flies teach us that piRNAs protect the germline from transposons and repetitive sequenc...

Ferroptosis: a regulated cell death nexus linking metabolism, redox biology and disease

Abstract: Dr. Stockwell will describe the discovery of ferroptosis, a form of regulated cell death characterized by the iron-dependent accumulation of lethal lipid hydroperoxides.  Current data suggest that ferroptosis is an ancient vulnerability caused by the evolution of cells with polyunsatura...

Small interfering RNA in replication, recombination and repair

Rob Martienssen is investigating the role of heterochromatin reprogramming and RNA interference in plant germ cells. These mechanisms reveal and regulate transposable elements, but they also play important roles in meiosis and reproductive fate.

Neural stem cells and brain development: From Drosophila to humans

The human brain is the most fascinating and most complex organ of all. Despite this enormous complexity, the billions of neurons in our brain arise from a limited number of progenitors following a specific set of lineage decisions. We combine Drosophila genetics with 3D organoid cultures derived ...

Stem cell-grown organoids as models for human disease

The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We originally defined Lgr5 as a Wnt target gene, transcribed in colon cancer cells. Two knock-in alleles revealed exclusive expression of Lgr5 in cycling, columnar cells at the crypt base. Using lineage tracing e...

Breast cancers are communities of clones and communities of cells

Professor Caldas holds the Chair of Cancer Medicine at the University of Cambridge since 2002. He heads the Breast Cancer Functional Genomics Laboratory at the Cancer Research UK Cambridge Research Institute. He is an Honorary Consultant Medical Oncologist at Addenbrooke's Hospital, and Director ...

To the edge of necroptosis and back

Publications: Gong, Y., Guy, C. Olauson, H., Becker, J.U., Yang, M., Fitzgerald, P., Linkermann, A., and Green, D.R.  ESCRT-III acts downstream of MLKL to regulate necroptotic cell death and its consequences.  Cell, in press. Quarato, G., Guy, C.S., Grace, C.R., Llambi, F., Nourse, A., Rodr...

Integration of actin dynamics and adhesion in cell migration

Clare Waterman graduated from the Mount Holyoke college with a B.A. in biochemistry in 1989, received an M.S. in exercise science in 1991 from the University of Massachusetts, and received her Ph.D. in cell biology from the University of Pennsylvania in 1995. Prior to joining the NHLBI, she spent...

The dynamic epitranscriptome: Encoding the fate and function of mRNA with reversible nucleotide modifications

An emerging concept in gene expression regulation is that a diverse set of modified nucleotides is found internally within mRNA, and these modifications constitute an epitranscriptomic code.  Our transcriptome-wide map of N6-methyladenosine (m6A) provided the initial understanding of the pervasiv...

Epigenetics evolution related to chromatin

Harmit Malik got his degree in Chemical Engineering from the Indian Institute of Technology in Mumbai graduated as MSc in Chemical Engineering from the Technical University. He was then awarded a PhD in Biology from the University of Rochester for his research on the evolutionary origins of retro...

A small RNA-based innate immune system guards the integrity of germ cell genomes

PIWI-family proteins and their associated small RNAs (piRNAs) act in an evolutionarily conserved innate immune mechanism that provides an essential protection for germ cell genomes against the activity of mobile genetic elements. piRNA populations comprise a molecular definition of transposons th...

Lessons from a lifetime researching developmental biology

Peter Lawrence, Cambridge University, UK This seminar is a part of the 7th course on "DEVELOPMENTAL BIOLOGY COURSE: From Stem Cells to Morphogenesis" (October 10-21, 2016) which takes place at Institut Curie - Paris, Amphitheater BDD. More information here. Organizers: A. Bardin, Y. Bellaïc...

How Mutations Activate a Telomerase Gene and Help Drive Cancer

How Mutations Activate a Telomerase Gene and Help Drive Cancer

Signatures of Mutational Processes in Cancer

All cancers are caused by somatic mutations. However, the processes underlying the genesis of somatic mutations in human cancer are remarkably poorly understood. Recent large-scale cancer genome sequencing initiatives have provided us with new insights into these mutational processes through the ...

Cancer drivers and dependencies

Cancer arises through an evolutionary process whereby normal cells acquire mutations that erode growth controls, leading to the expansion of aberrantly proliferating cells. Such mutations activate oncogenes or inactivate tumor suppressors, each bestowing new capabilities to emerging tumors. Still...

Responsible Conduct of Research: from bench to paper, and beyond

Publishers and Researchers have a common interest and a shared responsibility in promoting the integrity of the research process, and to ensure that it is carried out ethically. I will present a personal perspective on the issues surrounding reproducibility and responsible publication, informed b...

Mechanisms of endosome biogenesis, fusion and signalling

A major challenge in biological research is to integrate multiple levels of complexity, hierarchically ordered from molecules to molecular assemblies, to organelles, cells, tissues, organs and entire organisms. We have previously demonstrated that the small GTPase Rab5 is a master regulator of ea...

Revealing novel cell types and cell-cell interactions using single-cell transcriptomics

Understanding the development and function of an organ requires the characterization of all of its cell types. Traditional methods for visualizing and isolating sub-populations of cells are based on mRNA or protein expression of only few known marker genes. The unequivocal identification of a spe...

Translational Research - Drug resistance related to the tumor microenvironment : strategies for improving the effectiveness of chemotherapy

Chromatin dynamics at gene promoters abd centromeres: a tale of two histone variants

Carl Wu continues to develop a broad range of biochemical methods designed to probe key features of chromatin structure common to all eukaryotes. At Janelia, he is working collaboratively with colleagues using advanced microscopy to image histone and chromatin dynamics in vitro and in live cells.

Y-a-t-il un avenir pour les essais randomisés en oncologie ?

 La présentation orale se déroulera en français.  

Normal stem cell divisions, cancer incidence, and driver gene mutations

Cristian Tomasetti (joint work with Bert Vogelstein) Cancer arises through the sequential accumulation of mutations in oncogenes and tumor suppressor genes.  We show that the incidence of many cancers is strongly correlated (0.80; P < 1.8 × 10-6) with the lifetime number of divisions of the no...

Spatial and temporal limits of genome surveillance: Implications for cancer origin and treatment

Our laboratory is interested in how are proteins that guard the integrity of the human genome wired into functional pathways, and how are these pathways organized in the three-dimensional space of the cell nucleus. We are addressing these issues by high-content imaging of DNA damage responses in ...

Sorting of proteins and RNA in the secretory pathway

Dr. Randy Schekman is a Professor in the Department of Molecular and Cell Biology at the University of California, Berkeley, and an Investigator of the Howard Hughes Medical Institute. At Berkeley, he developed a genetic and biochemical approach to the study of eukaryotic membrane trafficking. In...

Molecular basis of polarity in single and collectively migrating cells

The logic of how cells polarize during cell migration is not yet understood. The seminar will focus on the molecular mechanisms of how Rho family small GTPases polarize migrating neutrophils as well as on the key role of actin fingers in controlling polarization during collective migration of end...

Connecting the machineries of the cell fate determination and tumor suppression in mammary stem cells

Numb is a cell fate determinant that by asymmetrically partitioning at mitosis controls binary cell fate decisions. In human breast cancers, there is frequent loss of Numb expression, due to its exaggerated ubiquitination and ensuing degradation. This causes alterations in two major downstream pa...

Beyond cancer: Illuminating a role for p53 in the development syndrome CHARGE

The p53 gene is mutated in at least half of all human cancers, underscoring its critical role in tumor suppression. p53 is a cellular stress sensor, responding to diverse insults such as DNA damage, hyperproliferative signals, and hypoxia by inducing growth arrest or apoptosis, responses thought ...

"Insights into dynamic instability and drug stabilization from the high resolution structures of microtubules in different states"

Dynamic instability, the stochastic switching between growth and shrinkage, is essential for microtubule function. This behavior is driven by GTP hydrolysis in the microtubule lattice, and is inhibited by anticancer agents like Taxol.  I will be reporting on our new insights into the mechanism of...

Mechanisms of Molecular Motor Proteins

Conférence par Ronald D. Vale, professeur à l'université de Californie à San Francisco, dans le département de pharmacologie cellulaire et moléculaire dont il est directeur. Venez nombreux à cet événement dans le cadre des séminaires institutionnels : "Marie Curie Seminars" ! Entrée libre

"Glimpses into Data Driven Medicine: Embracing Complexity"

Conférence de Stephen H. Friend (MD, PhD), président, co-fondateur et directeur de Sage Bionetworks. Venez nombreux à cette conférence inaugurale, qui ouvre une nouvelle série prestigieuse de séminaires institutionnels : "Marie Curie Seminars" ! Entrée libre